Page 6 - Fifth Report on Human Biomonitoring of Environmental Chemicals in Canada

15 Summaries and results for volatile organic compounds

15.1 Benzene

Benzene (CASRN 71-43-2) is a colourless liquid and volatile organic compound (VOC) that is naturally present in ambient air at low concentrations (Health Canada, 2009). It was first isolated and synthesized in the early 1800s. Today, it is commercially recovered from both coal and petroleum sources for industrial applications (ATSDR, 2007).

Benzene is used widely in industry as a solvent and as an intermediate in the production of a variety of chemicals, with typical end products including plastics and elastomers, phenol and acetone, and nylon resins (ATSDR, 2007; Environment Canada and Health Canada, 1993). Benzene is also used at various stages in the manufacturing of synthetic fibres, rubbers, lubricants, dyes, detergents, drugs, and pesticides (ATSDR, 2007).

Benzene is released to the environment from natural and anthropogenic sources. It is naturally present in crude oil, and is formed during the incomplete combustion of organic materials (Environment Canada and Health Canada, 1993). Benzene enters the environment as a result of natural processes including petroleum seepage, weathering of rock and soil, volcanic activity, forest fires, and releases from plant life (Environment Canada and Health Canada, 1993). Anthropogenic sources include the production, storage, use, and transport of isolated benzene, crude oil, and other petroleum products. Examples include evaporative releases from gasoline at service stations and combustion by-products in the form of motor vehicle exhaust (Health Canada, 2009). Natural sources are generally considered to contribute less benzene to the environment than anthropogenic sources (Environment Canada and Health Canada, 1993).

The most common route of exposure to benzene for the general population is inhalation; exposure is attributed predominantly to indoor air because indoor levels of benzene generally exceed those outdoors (Health Canada, 2010a; Health Canada 2010b; Health Canada, 2012; Health Canada, 2013a), and because people typically spend more time indoors than outdoors (Health Canada, 2013b). Exposure to benzene in air accounts for an estimated 98% to 99% of total benzene intake for Canadian non-smokers (Health Canada, 2009). Inside residences, benzene levels in air have been shown to be higher for homes with attached garages, or where smoking occurs (Héroux et al., 2008; Héroux et al., 2010; Wheeler et al., 2013; Mallach et al., 2016). Various marketplace products containing benzene can also contribute to its presence in indoor air including stored combustion equipment, air fresheners, incense, candles, mothballs, building materials and cleaning products (Won et al., 2013; Won et al. 2014; Won et al., 2015; Won and Yang, 2012; Environment Canada and Health Canada, 1993). Outdoor benzene exposure sources include motor vehicle exhaust, gasoline service stations, and gasoline storage facilities (ATSDR, 2007). Foods, beverages, and tap water are not major sources of benzene exposure for the general population (ATSDR, 2007; Health Canada, 2009).

Following inhalation, benzene is readily absorbed into the blood and distributed throughout the body, concentrating primarily in adipose tissue and bone marrow (EPA, 2002; ATSDR 2007). Benzene metabolism occurs mainly in the liver, but also in other tissues such as bone marrow. It is metabolized into several reactive metabolites, including benzene oxide (Environment Canada and Health Canada, 1993; EPA, 2002; McHale et al., 2012). After initial formation of benzene oxide, metabolism can branch into several alternative pathways: spontaneous rearrangement produces phenol, a major product; reaction with glutathione ultimately forms S-phenylmercapturic acid (S-PMA); and an iron-catalyzed reaction leads to the formation of trans,trans-muconic acid (t,t-MA) (EPA, 2002). Excretion of benzene occurs via exhalation of benzene from the lungs and as conjugated metabolites in urine; all benzene metabolites may be conjugated with sulphate or glucuronic acid (EPA, 2002). Phenol, S-PMA, and t,t-MA are considered urinary biomarkers of recent benzene exposure (Boogaard and van Sittert, 1995; Qu et al., 2005; Weisel, 2010). Measurements of t,t-MA and S-PMA are more sensitive and reliable indicators of benzene exposure because urinary phenol may be a result of dietary or environmental exposure to phenol or other phenolic compounds (ATSDR, 2007). Benzene levels in blood are a reliable biomarker of benzene exposure and reflect recent exposure (Arnold et al., 2013; Weisel, 2010).

Benzene is known to cause a number of health effects in humans, with the specific adverse effects dependent upon the concentration and duration of exposure. Exposure to benzene can be hematotoxic in humans and laboratory animals, with bone marrow being the principal target organ (EPA, 2002). Available data indicate that benzene metabolites produced in the liver may be carried to bone marrow, where hematotoxicity occurs (EPA, 2002). In rodents, chronic inhalation exposure to benzene has been shown to cause leukemia (EPA, 2002). Epidemiological studies provide strong evidence of an association between exposure to high levels of benzene and leukemia risk in occupationally exposed humans (EPA, 2002). Benzene has been classified as carcinogenic to humans by Environment Canada and Health Canada (Group I) and the International Agency for Research on Cancer (Group 1) (Environment Canada and Health Canada, 1993; IARC, 2012). A common mode of action has not been established for hematotoxic and carcinogenic effects; however, it is generally accepted that acute myelogenous leukemia and non-cancer effects are caused by one or more reactive metabolites of benzene (ATSDR, 2007; McHale et al., 2012; Meek and Klaunig, 2010; Smith, 2010).

Globally, benzene has become one of the most intensively regulated substances (Capleton and Levy, 2005). Benzene is listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999 and is a candidate for full life cycle management to prevent or minimize its release into the environment (Canada, 1999; Environment Canada and Health Canada, 1993). In Canada, regulations have been put in place to limit the concentration of benzene in gasoline fuel (Canada, 1997; Environment Canada, 1998) and reduce emissions from on-road (Canada, 2003; Canada, 2015) and off-road (Canada, 2013; Canada, 2017) engines and vehicles. The Gasoline and Gasoline Blend Dispensing Flow Regulations, implemented in 2001, also limit emissions of benzene and other VOCs into the environment during the refuelling of on-road vehicles (Canada, 2000). In 2000–2001, the Canadian Council of Ministers of the Environment (CCME) endorsed the Canada-wide standard for benzene, requiring a reduction in total benzene emissions from industrial facilities and the use of best management practices (CCME, 2000; CCME, 2001). With the implementation of these standards, emissions of benzene from industry to ambient air fell by 71% between 1995 and 2008 (CCME, 2012). Benzene is also identified as being prohibited on the List of Prohibited and Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient Hotlist or simply the Hotlist), an administrative tool that Health Canada uses to communicate to manufacturers and others that certain substances, when present in a cosmetic, may not be compliant with requirements of the Food and Drugs Act or the Cosmetic Regulations (Health Canada, 2018).

The Government of Canada has also taken a number of actions to address VOCs, a large class of compounds that includes benzene. As a class, they are environmental and health concerns because of their contribution to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013).

Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, has developed a guideline for Canadian drinking water quality that establishes the maximum acceptable concentration for benzene in drinking water based on cancer end points and is considered protective of both cancer and non-cancer effects (Health Canada, 2009). Health Canada has identified benzene as a priority indoor air contaminant and has developed a guidance document for benzene in residential indoor air (Health Canada, 2013b). On the basis that there may be a low but non-negligible cancer risk at indoor exposure levels measured in Canadian homes in Health Canada studies, it is recommended that individuals take actions to reduce their exposure to benzene indoors as much as possible. In particular, exposure reduction strategies have been recommended that target attached garages and indoor smoking as primary sources of benzene indoors.

Benzene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) cycle 3 (2012–2013), cycle 4 (2014–2105), and cycle 5 (2016–2017) participants aged 12–79 years. Data are presented as µg/L blood for benzene. Finding a measurable amount of benzene in blood can be an indicator of exposure to benzene and does not necessarily mean that an adverse health effect will occur.

Benzene metabolites, t,t-MA and S-PMA, were analyzed in the urine of CHMS cycle 2 (2009–2011), cycle 3 (2012–2013), and cycle 4 (2014–2015) participants aged 3–79 years (Health Canada, 2017).

Benzene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Statistics Canada, 2013; Wheeler et al., 2013; Zhu et al., 2013), cycle 3 (2012–2013) (Statistics Canada, 2015), and cycle 4 (2014–2015), and in tap water from households in cycles 3 and 4. Further details on the indoor air and tap water studies are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air and tap water data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.1.1: Benzene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.1.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2488 88.4
(76.6–94.7)
0.035
(0.025–0.050)
<LOD 0.039
(0.030–0.049)
0.15
(0.12–0.19)
0.24
(0.18–0.29)
4 (2014–2015) 2354 94.6
(89.1–97.4)
0.034Table 15.1.1 footnote E
(0.024–0.050)
0.0093Table 15.1.1 footnote E
(<LOD–0.013)
0.033Table 15.1.1 footnote E
(0.017–0.049)
0.14
(0.090–0.19)
0.21
(0.16–0.26)
5 (2016–2017) 2436 74.5
(58.9–85.6)
0.037
(0.028–0.047)
<LOD 0.035
(0.027–0.043)
0.15
(0.099–0.19)
0.20
(0.15–0.25)
Males, 12–79 years
3 (2012–2013) 1245 89.0
(78.1–94.8)
0.036
(0.025–0.052)
<LOD 0.040
(0.030–0.049)
0.15
(0.13–0.18)
0.24
(0.18–0.30)
4 (2014–2015) 1164 95.2
(89.8–97.9)
0.037
(0.026–0.054)
0.0097Table 15.1.1 footnote E
(<LOD–0.015)
0.036Table 15.1.1 footnote E
(0.019–0.054)
0.16
(0.10–0.21)
0.23
(0.15–0.31)
5 (2016–2017) 1216 74.8
(60.4–85.2)
0.041
(0.031–0.052)
<LOD 0.037
(0.026–0.047)
0.16
(0.14–0.19)
0.23
(0.16–0.31)
Females, 12–79 years
3 (2012–2013) 1243 87.8
(73.5–94.9)
0.035Table 15.1.1 footnote E
(0.024–0.051)
<LOD 0.038
(0.028–0.049)
0.17Table 15.1.1 footnote E
(0.093–0.24)
0.23Table 15.1.1 footnote E
(0.11–0.35)
4 (2014–2015) 1190 93.9
(87.5–97.1)
0.032Table 15.1.1 footnote E
(0.021–0.048)
0.0090Table 15.1.1 footnote E
(<LOD–0.013)
0.030Table 15.1.1 footnote E
(0.015–0.045)
0.13Table 15.1.1 footnote E
(0.071–0.19)
0.19
(0.14–0.25)
5 (2016–2017) 1220 74.2
(56.5–86.5)
0.033
(0.025–0.043)
<LOD 0.034
(0.026–0.042)
0.096Table 15.1.1 footnote E
(0.051–0.14)
0.19Table 15.1.1 footnote E
(0.099–0.28)
12–19 years
3 (2012–2013) 750 86.0
(73.0–93.3)
0.028Table 15.1.1 footnote E
(0.019–0.040)
<LOD 0.034
(0.025–0.043)
0.084
(0.063–0.10)
0.12
(0.076–0.16)
4 (2014–2015) 663 93.0
(83.6–97.2)
0.028Table 15.1.1 footnote E
(0.019–0.041)
0.0087Table 15.1.1 footnote E
(<LOD–0.014)
0.029Table 15.1.1 footnote E
(0.013–0.045)
0.087
(0.068–0.11)
0.12
(0.074–0.16)
5 (2016–2017) 790 74.4
(55.5–87.1)
0.032
(0.025–0.040)
<LOD 0.033
(0.025–0.041)
0.072
(0.055–0.088)
0.099
(0.085–0.11)
20–39 years
3 (2012–2013) 548 90.2
(73.6–96.8)
0.037Table 15.1.1 footnote E
(0.023–0.059)
<LOD 0.040
(0.027–0.054)
0.13
(0.080–0.17)
0.18
(0.14–0.22)
4 (2014–2015) 568 96.5
(91.2–98.7)
0.033Table 15.1.1 footnote E
(0.021–0.051)
0.0097Table 15.1.1 footnote E
(<LOD–0.014)
0.031Table 15.1.1 footnote E
(0.0097–0.052)
0.12
(0.074–0.16)
0.17Table 15.1.1 footnote E
(0.11–0.24)
5 (2016–2017) 559 78.7
(61.9–89.3)
0.041
(0.032–0.053)
<LOD 0.038
(0.027–0.049)
0.17
(0.13–0.21)
0.20
(0.15–0.25)
40–59 years
3 (2012–2013) 598 89.7
(79.1–95.2)
0.040
(0.029–0.055)
<LOD 0.039
(0.028–0.050)
0.23
(0.16–0.31)
0.40Table 15.1.1 footnote E
(0.24–0.56)
4 (2014–2015) 575 93.9
(85.3–97.6)
0.041Table 15.1.1 footnote E
(0.027–0.062)
0.010Table 15.1.1 footnote E
(<LOD–0.015)
0.037Table 15.1.1 footnote E
(0.014–0.060)
0.18
(0.13–0.22)
0.29Table 15.1.1 footnote E
(0.18–0.40)
5 (2016–2017) 539 72.4
(55.1–84.9)
0.036
(0.026–0.051)
<LOD 0.035
(0.025–0.045)
0.15Table 15.1.1 footnote E
(0.071–0.23)
0.23
(0.15–0.31)
60–79 years
3 (2012–2013) 592 84.6
(69.6–93.0)
0.031Table 15.1.1 footnote E
(0.020–0.047)
<LOD 0.038
(0.026–0.051)
0.13
(0.085–0.17)
0.20
(0.16–0.24)
4 (2014–2015) 548 93.4
(87.9–96.5)
0.031
(0.023–0.042)
0.0084Table 15.1.1 footnote E
(<LOD–0.013)
0.030
(0.021–0.039)
0.13
(0.085–0.17)
0.24Table 15.1.1 footnote E
(0.15–0.33)
5 (2016–2017) 548 71.4
(54.4–84.0)
0.034
(0.025–0.045)
<LOD 0.032
(0.023–0.041)
0.12Table 15.1.1 footnote E
(0.048–0.19)
0.22Table 15.1.1 footnote E
(0.097–0.35)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.0070, 0.0070, and 0.022 μg/L, respectively.

References

15.2 Carbon tetrachloride

Carbon tetrachloride (CASRN 56-23-5), also known as tetrachloromethane, is a colourless, non-flammable, heavy liquid with a characteristic sweet, aromatic, non-irritating odour (IARC, 1999; Health Canada, 2010a). It is a haloalkane and is considered a volatile organic compound (VOC). Carbon tetrachloride is generally produced industrially either by chlorination of methane or monochloromethane, or by perchlorination or chlorinolysis (chlorination at pyrolytic temperatures) of low molecular-weight (C1–C3) hydrocarbons (e.g., methane) or other chlorinated hydrocarbons (e.g., methylene chloride) (ATSDR, 2005; Holbrook, 2000). Carbon tetrachloride is no longer manufactured in Canada, and the quantity of carbon tetrachloride imported into Canada has generally been declining, though at a much more gradual rate since 2006 (Statistics Canada, 2018).

Currently, carbon tetrachloride is only permitted to be imported into Canada for limited use as a feedstock/intermediate in chemical synthesis (see below). In the past, it was mainly used as a feedstock in the production of chlorofluorocarbons (e.g., for refrigerant use), but was also used in the 20th century in industrial and domestic degreasers, fire extinguishers, dry-cleaning agents, and grain fumigants. Other past uses include as a solvent for oils, fats, lacquers, varnishes, rubber waxes, and resins, and as an ingredient in pharmaceutical products (ATSDR, 2005; Health Canada, 2010a).

Carbon tetrachloride is not known to occur naturally. Most atmospheric carbon tetrachloride is a result of direct releases to the atmosphere; however, it can also form in the troposphere from photochemical reactions with chlorinated alkenes (ATSDR, 2005; Health Canada, 2010a). Carbon tetrachloride disperses rapidly in air due to its very high volatility and persists in air due to its very slow atmospheric degradation rate, with an estimated lifetime of 30 to 100 years (NTP, 2016). Indoor air may contain higher concentrations of carbon tetrachloride as a result of volatilization from contaminated drinking water and/or from the use of discontinued household products containing carbon tetrachloride (ATSDR, 2005). Carbon tetrachloride concentrations measured in Canadian homes were found to be similar in indoor and outdoor air in studies conducted by Health Canada over the last decade (Health Canada, 2013; Health Canada 2012; Health Canada, 2010b; Health Canada, 2010c). Limited evidence suggests that the use of chlorine bleach may contribute to the presence of carbon tetrachloride in indoor air (NTP, 2016; Odabasi, 2008). In some areas where historical contamination has occurred, drinking water may be contaminated with carbon tetrachloride; concentrations of carbon tetrachloride in groundwater sources are expected to be higher than in surface water due to the limited potential for volatilization and biodegradation in groundwater systems (Health Canada, 2010a).

Canadians may be exposed to carbon tetrachloride from its continued presence in the environment from historical releases, from permitted industrial processes, or from the use of old or discontinued household products (ATSDR, 2005; Health Canada, 2010a). While inhalation of ambient and indoor air is the primary route of exposure for the general population, oral exposure may also occur from ingestion of contaminated drinking water, and dermal exposure may occur during bathing or showering (ATSDR, 2005; Health Canada, 2010a). Exposure of Canadians to carbon tetrachloride from foods is not expected for a number of reasons: it is no longer used for grain fumigation in Canada (and its use as such in other countries is limited); the Canadian Pest Management Regulatory Agency has prohibited its use as a formulant in pest control products in Canada; and it is not frequently detected in foods (ATSDR, 2005; FDA, 2006; Health Canada, 2006; Health Canada, 2010a).

Carbon tetrachloride is rapidly absorbed orally and by inhalation, and to a lesser extent dermally. Based on animal studies, a small amount of carbon tetrachloride is expired in breath directly following absorption, with the remainder entering systemic circulation and being distributed to all major organs. The highest concentrations are found in fat and in organs or tissues with high fat content, such as liver, kidney, brain, and bone marrow, as well as in the lungs and adrenals (ATSDR, 2005; Health Canada, 2010a). Carbon tetrachloride can transiently accumulate in fatty/adipose tissues, where it is slowly released back into the blood stream (CDC, 2009; OECD, 2011). It may undergo hepatic metabolism via cytochrome P450 oxygenases. Carbon tetrachloride is excreted primarily in exhaled air and in the feces, and in lower amounts in the urine; it is eliminated in exhaled breath primarily as the unchanged parent compound and to a lesser extent as CO2 or chloroform. It is eliminated in feces and urine as urea and other metabolites (ATSDR, 2005).

Acute inhalation or oral exposures to carbon tetrachloride at high dose levels in humans have been associated with neurological effects involving central nervous system depression with symptoms such as headaches, dizziness, and weakness, and in severe cases tremor, blurred vision, drowsiness, seizures, loss of consciousness, and mortality from suppression of respiratory centres (ATSDR 2005). A number of other adverse health effects in humans have been associated with acute inhalation or oral exposures, such as decreased serum iron, gastrointestinal irritation, nausea, proteinuria, increased hepatic bilirubin, and liver necrosis (Health Canada, 2010a). Hepatotoxicity is the major chronic effect of exposure to carbon tetrachloride by any route in humans, because of the higher sensitivity of the liver due to the abundance of CYP2E1 enzymes and other cytochromes that have been shown to activate carbon tetrachloride into reactive metabolites (ATSDR 2005). Symptoms of liver injury in humans include jaundice and swollen or tender liver. Based on animal studies, chronic liver effects may include steatosis, fibrosis, cirrhosis, and necrosis (ATSDR 2005). The kidney is another sensitive target organ; in humans, kidney injury is often observed at the same exposure levels as liver injury. A principal symptom in severe cases is reduced urinary output, which can lead to azotemia, hypertension, and pulmonary edema. Chronic animal studies have demonstrated kidney effects, including nephropathy and reduction in kidney enzyme activity.

Occupational studies have reported associations between exposure to halogenated solvents and reduced fertility and spontaneous abortions, although the extent of involvement of carbon tetrachloride in these effects is unclear (CDC, 2009). Animal studies have not consistently demonstrated reproductive toxicity in the absence of maternal toxicity (CDC, 2009). Carbon tetrachloride is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B) based on sufficient evidence of carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 1999).

Under the Montreal Protocol on Substances that Deplete the Ozone Layer,an international agreement reached in 1987, the production of chlorofluorocarbons was mandated to be phased out by 2030 (UNEP, 2019). To meet these commitments, the manufacture, import and export of carbon tetrachloride has been prohibited in Canada since 1995, except for its import as a feedstock in the synthesis of chlorofluorocarbons (CFCs), hydrochlorofluorocarbons (HCFCs), and hydrofluorocarbons (HFCs) (Environment and Climate Change Canada and Health Canada, 2016; Health Canada, 2010a).

Carbon tetrachloride is listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999, and is a risk-managed substance that entails a full life cycle management approach to prevent or minimize its release into the environment (Canada, 1999). Canada has developed regulations to manage the risks associated with carbon tetrachloride that control the export, import, manufacture, sale, and use of ozone-depleting substances as well as products containing or designed to contain them (Canada, 2003; Canada, 2016). Carbon tetrachloride is also identified as being prohibited on the List of Prohibited and Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient Hotlist or simply the Hotlist), an administrative tool that Health Canada uses to communicate to manufacturers and others that certain substances, when present in a cosmetic, may not be compliant with requirements of the Food and Drugs Act or the Cosmetic Regulations (Health Canada, 2018).

Carbon tetrachloride is also part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013). In 2017, Health Canada published an Indoor Air Reference Level (IARL) for carbon tetrachloride (Health Canada, 2017b).

Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, has also developed a guideline for Canadian drinking water quality that establishes a maximum acceptable concentration (MAC) for carbon tetrachloride that is protective of human health and takes into consideration all exposures from drinking water (including ingestion as well as inhalation and dermal absorption during showering and bathing) (Health Canada, 2010a; Health Canada, 2017a).The sale and use of pesticides is regulated in Canada by PMRA under the Pest Control Products Act (Canada, 2002). PMRA has prohibited the use of carbon tetrachloride as a formulant in pest control products in Canada due to it being an ozone-depleting chemical (PMRA, 2006).

Carbon tetrachloride was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 in cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of carbon tetrachloride in blood can be an indicator of recent exposure to carbon tetrachloride and does not necessarily mean that an adverse health effect will occur.

Carbon tetrachloride was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013).

Table 15.2.1: Carbon tetrachloride — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.2.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2574 36.3
(28.7–44.6)
<LOD <LOD 0.0071
(0.0060–0.0083)
0.0086
(0.0071–0.010)
Males, 12–79 years
5 (2016–2017) 1281 40.3
(31.9–49.3)
<LOD <LOD 0.0072
(0.0057–0.0086)
0.0089
(0.0063–0.012)
Females, 12–79 years
5 (2016–2017) 1293 32.2
(24.2–41.5)
<LOD <LOD 0.0071
(0.0059–0.0083)
0.0083
(0.0071–0.0095)
12–19 years
5 (2016–2017) 834 34.7
(24.9–45.9)
<LOD <LOD 0.0072
(0.0057–0.0087)
0.0088
(0.0065–0.011)
20–39 years
5 (2016–2017) 591 38.4
(26.9–51.4)
<LOD <LOD 0.0071
(0.0062–0.0080)
0.0080
(0.0070–0.0090)
40–59 years
5 (2016–2017) 568 36.7
(25.9–49.1)
<LOD <LOD 0.0079
(0.0053–0.010)
0.0093Table 15.2.1 footnote E
(0.0052–0.013)
60–79 years
5 (2016–2017) 581 33.2
(27.7–39.2)
<LOD <LOD 0.0067
(0.0060–0.0075)
0.0082
(0.0073–0.0092)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 0.005 μg/L.

References

15.3 1,4-Dichlorobenzene

1,4-Dichlorobenzene (CASRN 106-46-7), also known as para-dichlorobenzene, is a solid ranging from colourless to white that sublimates at room temperature, producing a characteristic penetrating odour that smells like moth balls (ATSDR, 2006; IARC, 1999;). It is a halogenated aromatic hydrocarbon and is considered a volatile organic compound (VOC). It is a high-production volume industrial chemical typically produced by reacting liquid benzene with gaseous chlorine in the presence of a catalyst, followed by crystallization and distillation (ATSDR, 2006; Beck and Löser, 2012; EPA, 2018; IARC, 1999;OECD, 2018). 1,4-Dichlorobenzene has been manufactured in Canada and is also imported into the country, although the quantity of dichlorobenzenes (ortho, meta, and para isomers) imported into Canada has been decreasing since 1995 (Environment Canada and Health Canada, 1993; 2003; Statistics Canada, 2018).

Major uses of 1,4-dichlorobenzene include moth-control products (as an active ingredient in registered pesticides in Canada) and urinal and toilet rim blocks (i.e., room deodorants). It is also used as an intermediate in the production of polyphenylene sulfide resin and 1,2,4-trichlorobenzene (ATSDR, 2006; CAREX Canada, 2018; Environment Canada and Health Canada, 1993). It also may be used as a disinfectant, as an intermediate in the production of pigments and dyes, and as an ingredient in certain pharmaceuticals and resin-bonded abrasives (CAREX Canada, 2018).

Chlorinated benzenes are not known to occur naturally (ATSDR, 2006; IARC, 1999). Concentrations of 1,4-dichlorobenzene in indoor air may be significantly higher than in ambient air (ATSDR, 2006; Health Canada, 2010c; Health Canada 2010d; Health Canada, 2012; Health Canada, 2013; NTP, 2016). Sources of indoor air exposure include air fresheners, candles, furniture, and various building materials (Won et al., 2013; Won et al., 2014; Won and Lustyk, 2011; Won and Yang, 2012). Major sources of 1,4-dichlorobenzene in ambient air are volatilization during its consumer or commercial use, and emissions from municipal and industrial waste sites and incinerator facilities (ATSDR, 2006; IARC, 1999).

While inhalation of ambient and indoor air is the primary route of exposure for the general population, exposure may also occur from ingestion of foods and drinking water. 1,4-Dichlorobenzene has been found in a variety of foods sampled in Canada, including soft drinks, butter, margarine, peanut butter, flour, pastry mixes, and cow's milk (IARC, 1999), as well as in the breast milk of Canadian women (Mes et al., 1986). The U.S. Food and Drug Administration Total Diet Study reported that 1,4-dichlorobenzene was identified in 33 different food items, but concluded that concentrations were generally low and exposures were less than from air (FDA, 2006; NTP, 2016). 1,4-Dichlorobenzene is the main dichlorobenzene isomer found in drinking water, probably resulting largely from its use in urinal/toilet blocks and releases or spills from industrial effluents (Health Canada, 2017a; IARC, 1999). 1,4-Dichlorobenzene has been detected at low concentrations in treated drinking water, including in Canadian samples, but this is thought to be a minor pathway for human exposure (ATSDR, 2006; Health Canada, 1987; Oliver and Nicol, 1982; Otson et al., 1982).

1,4-Dichlorobenzene is rapidly and almost completely absorbed orally and by inhalation, but not appreciably through skin contact (ATSDR, 2006; HSDB, 2008). Quantitative data on absorption kinetics by inhalation in animals and humans are not available; however, numerous human and animal studies detecting 1,4-dichlorobenzene or its metabolites in blood, urine, adipose tissue, and other peripheral tissues, as well as in breast milk, provide evidence of its absorption and distribution (ATSDR, 2006). Animal studies indicate that 1,4-dichlorobenzene temporarily accumulates in adipose tissue before being rapidly distributed to the rest of the body, with the highest levels found in fat, liver, and kidney (ATSDR, 2006). Animal studies also demonstrate that 1,4-dichlorobenzene primarily undergoes oxidative hepatic metabolism by epoxidation and hydrolysis followed by phase II metabolism to form sulphate and glucuronic conjugates of 2,5-dichlorophenol, which are excreted almost exclusively in urine, with small amounts eliminated through biliary excretion and negligible elimination in expired breath. These studies also indicate that elimination occurs in the form of metabolites, rather than as the parent compound, over a period of several days post-exposure (ATSDR, 2006; HSDB, 2008).

In humans, 1,4-dichlorobenzene can cause ocular, nasal, and respiratory irritation (OECD, 2003). Acute inhalation exposure in humans has been associated with symptoms of nausea, headache, and vomiting (ATSDR, 2006). Based on clinical information, central nervous system depression can result following inhalation of very high concentrations, while in severe cases, dizziness, headache, facial twitching, vomiting, weight loss, and cirrhosis can occur (HSDB, 2008). Chronic exposure in humans may result in hepatotoxicity with symptoms of jaundice, cirrhosis, and possible death. Chronic inhalation studies in animals have reported mortality as well as liver, kidney, and respiratory effects (HSDB, 2008; IARC, 1999; OECD, 2003). 1,4-Dichlorobenzene is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B) based on sufficient evidence of carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 1999).

The Government of Canada conducted a Priority Substances List (PSL) scientific assessment on the impact of 1,4-dichlorobenzene exposure on humans and the environment and concluded that it was not entering the environment in quantities or under conditions that would constitute a danger to the environment on which human life depends, or to human life or health (Environment Canada and Health Canada, 1993). Based upon available data at the time, there was insufficient information to conclude whether it was entering the environment in quantities or under conditions that may be harmful to the environment. A follow-up PSL report concluded that 1,4-dichlorobenzene was not entering the environment in a quantity or at a concentration or under conditions that have or may have an immediate or long-term harmful effect on the environment or its biological diversity; therefore, it is not considered toxic as defined in paragraph 64(a) of the Canadian Environmental Protection Act, 1999 (Environment Canada and Health Canada, 2003).

Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, has also developed a maximum acceptable concentration (MAC) for 1,4-dichlorobenzene in Canadian drinking water that is protective of human health, as well as an aesthetic objective based on its odour threshold (Health Canada, 1987; Health Canada, 2017a). The guideline was developed based on the development of benign liver and adrenal gland tumours in animals (Health Canada, 1987; Health Canada, 2017a; NTP, 1986). In 2017, Health Canada published an Indoor Air Reference Level (IARL) for 1,4-dichlorobenzene (Health Canada, 2017b). 1,4-Dichlorobenzene is part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013).

The sale and use of 1,4-dichlorobenzene as a pesticide is regulated in Canada by Health Canada's Pest Management Regulatory Agency (PMRA) under the Pest Control Products Act (Canada, 2002). 1,4-Dichlorobenzene is an active ingredient in registered pest control products in Canada, namely in insecticides used to control moths and moth larvae (Health Canada, 2010b; Health Canada, 2019). PMRA evaluates the toxicity of pesticides and potential exposure to determine whether a pesticide should be registered for a specific use, and re-evaluates registered pesticides on a cyclical basis. In its most recent re-evaluation, PMRA determined that products containing 1,4-dichlorobenzene are acceptable for continued registration for sale and use in Canada, provided they are used according to label directions and specified risk-reduction measures are implemented (Health Canada, 2010b).

1,4-Dichlorobenzene was analyzed in whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of 1,4-dichlorobenzene in blood can be an indicator of recent exposure to 1,4-dichlorobenzene and does not necessarily mean that an adverse health effect will occur.

1,4-Dichlorobenzene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013), cycle 3 (2012–2013), and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.3.1: 1,4-Dichlorobenzene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.3.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2544 69.8
(61.2–77.2)
0.031
(0.024–0.040)
<LOD 0.024
(0.017–0.031)
0.24Table 15.3.1 footnote E
(0.091–0.38)
0.76Table 15.3.1 footnote E
(0.44–1.1)
Males, 12–79 years
5 (2016–2017) 1261 71.0
(62.8–78.1)
0.034
(0.025–0.047)
<LOD 0.027
(0.021–0.033)
Table footnote F 0.84Table 15.3.1 footnote E
(0.29–1.4)
Females, 12–79 years
5 (2016–2017) 1283 68.5
(58.6–77.0)
0.028
(0.021–0.039)
<LOD 0.022Table 15.3.1 footnote E
(<LOD–0.031)
0.20Table 15.3.1 footnote E
(0.12–0.28)
Table footnote F
12–19 years
5 (2016–2017) 827 65.9
(52.6–77.1)
0.028Table 15.3.1 footnote E
(0.019–0.040)
<LOD 0.021
(0.014–0.027)
0.26Table 15.3.1 footnote E
(0.082–0.44)
0.72Table 15.3.1 footnote E
(0.26–1.2)
20–39 years
5 (2016–2017) 582 72.6
(63.7–80.0)
0.033Table 15.3.1 footnote E
(0.023–0.049)
<LOD 0.029Table 15.3.1 footnote E
(0.018–0.040)
Table footnote F Table footnote F
40–59 years
5 (2016–2017) 562 68.0
(56.7–77.5)
0.029
(0.021–0.041)
<LOD 0.021
(0.015–0.028)
Table footnote F Table footnote F
60–79 years
5 (2016–2017) 573 70.1
(60.0–78.5)
0.033
(0.024–0.044)
<LOD 0.024
(0.019–0.030)
0.27Table 15.3.1 footnote E
(0.097–0.44)
Table footnote F

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 0.013 μg/L.

References

15.4 2,5-Dimethylfuran

2,5-Dimethylfuran (CASRN 625-86-5) is an alkylfuran with the appearance of a clear yellow oily liquid that has a pungent spicy, smoky, or ethereal/solvent-like odour (Burdock, 2010; Yang et al. 2016). It is produced commercially by acid-catalyzed dehydration of D-fructose from food material to 5-hydroxymethylfurfural, followed by consecutive hydrogenolysis over a copper-ruthenium catalyst (Lichtenhaler, 2012; Román-Leshkov et al., 2007). Advancements have been made in the biofuels sector to develop bulk scale processes to produce 5-hydroxymethylfurfural (and, thus, 2,5-dimethylfuran) from cellulosic biomass raw materials rather than food-based sources (Binder and Raines 2009; Lichtenhaler 2012).

2,5-Dimethylfuran is released to the environment—primarily to air—from natural and anthropogenic sources. Low levels of 2,5-dimethylfuran may be found in various foods, and it generally co-occurs with furan and other alkylfurans (e.g., 2-methylfuran) (Burdock, 2010; EFSA 2017). 2,5-Dimethylfuran is a Maillard product in foods (i.e., a product of heat-driven reactions between amino acids and sugars) and is formed by the thermal degradation of glucose (Heyns et al., 1966; Yang et al., 2016). 2,5-Dimethylfuran is not permitted as a food additive in Canada. It has been reported to occur either as a natural component of tobacco, a pyrolysis product (in tobacco smoke), or a tobacco additive (NTP, 2018). It has been measured in incense smoke and tobacco smoke, in the headspace above brewed coffee, as well as in Canadian and U.S. indoor air (Charles et al., 2008; EFSA, 2017; Eggert and Hanson, 2004; Pazo et al., 2016; Yang et al., 2016; Li et al., 2019). Although 2,5-dimethylfuran is a strong candidate as a next-generation biofuel, with an energetic content similar to gasoline, its current status in Canada for use as a biofuel is unknown (Lichtenhaler, 2012; Simmie and Würmel, 2013).

The general Canadian population is expected to be exposed to 2,5-dimethylfuran primarily through smoking, inhalation of indoor air, and diet. 2,5-Dimethylfuran is considered a reliable and specific tracer of environmental tobacco smoke in indoor air; levels in breath and blood have been used as indicators of smoking status (Alonso et al., 2010; Besalú et al., 2014; Bi et al., 2005; Blount et al., 2006; Charles et al., 2008; CDC, 2016). Blood levels of 2,5-dimethylfuran provide a rough estimate of the number of cigarettes smoked per day (CDC, 2016). It should be noted that concentrations of 2,5-dimethylfuran in urine may be non-specific in regard to the parent compound, and could, for example, also result from metabolism of hexane where such exposures may occur.

Experimental animal studies have shown that following exposure, 2,5-dimethylfuran is rapidly absorbed, metabolized, and excreted in urine, as with other alkylfurans (CDC, 2016; Williams and Bend, 2006). Specific data on the distribution of 2,5-dimethylfuran are lacking. However, a study using laboratory animals administered radiolabelled 2-methylfuran, a related alkylfuran, and reported distribution as liver > kidney > lung > blood, with most of it eliminated within 24 hours (Williams and Bend, 2006). Alkylfurans are metabolized by the CYP450 pathway to hydroxylated furans, which are then excreted in urine either as phase II conjugates or as corresponding ketones (Williams and Bend, 2006). They also have the potential to form reactive intermediates during metabolism. Alkylfurans can undergo ring opening epoxidation by mixed function oxidases in the liver, in the case of 2,5-dimethylfuran forming cis-enedione 3(Z)-hexene-2,5-dione, which can form adducts by binding with amino acids/proteins (EFSA, 2017; Williams and Bend, 2006). Based on human occupational and animal studies, 2,5-dimethylfuran is also a known urinary metabolite of n-hexane; together with 2,5-hexanedione and 4,5-dihydroxy-2-hexanone, it is one of its main metabolites in humans (EPA, 2005).

Available information on the health effects of 2,5-dimethylfuran is very limited. Furan, 2-methylfuran and 3-methylfuran share a common metabolic pathway and the ability to bind irreversibly to proteins. 2,5-Dimethylfuran can be considered a structural analogue of substances such as furan, 2-methylfuran, and furfuryl alcohol, and may have similar health effects (Phuong et al., 2012; Williams and Bend, 2006). Furan, 2-methylfuran, and 3-methylfuran demonstrate similar potencies for hepatotoxicity in animal studies, and the European Food Safety Authority (EFSA) (2017) assumed dose additivity of these substances in its risk determination. However, it was concluded that there was insufficient information in vivo to assume additivity for 2,5-dimethylfuran in producing this effect. There is evidence that 2,5-dimethylfuran induces chromosomal damage in vitro in mammalian cells, and limited evidence of its ability to induce DNA breaks in vivo (EFSA, 2017). 2,5-Dimethylfuran may also have neurotoxic potential, as it has been shown to induce in vitro cytotoxicity in Schwann neural cells, and may play a role in the neurotoxicity of hexane (Williams and Bend, 2006).

2,5-Dimethylfuran is also part of a larger class of volatile organic compounds (VOCs) that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has taken and proposed a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013).

2,5-Dimethylfuran was analyzed in whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of 2,5-dimethylfuran in blood can be an indicator of a recent exposure to 2,5-dimethylfuran and does not necessarily mean that an adverse health effect will occur.

2,5-Dimethylfuran was also analyzed in indoor air from households of CHMS participants in cycle 3 (2012–2013) and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.4.1: 2,5-Dimethylfuran — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.4.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2544 15.7
(12.9–18.9)
<LOD <LOD 0.085Table 15.4.1 footnote E
(0.039–0.13)
0.17
(0.12–0.21)
Males, 12–79 years
5 (2016–2017) 1270 21.5
(17.5–26.1)
<LOD <LOD 0.12
(0.082–0.16)
0.18
(0.14–0.21)
Females, 12–79 years
5 (2016–2017) 1274 9.9Table 15.4.1 footnote E
(6.4–15.2)
<LOD <LOD <LOD 0.14Table 15.4.1 footnote E
(0.045–0.23)
12–19 years
5 (2016–2017) 822 8.9Table 15.4.1 footnote E
(5.7–13.7)
<LOD <LOD <LOD <LOD
20–39 years
5 (2016–2017) 585 22.0
(16.4–28.9)
<LOD <LOD 0.12Table 15.4.1 footnote E
(0.057–0.17)
0.16
(0.11–0.20)
40–59 years
5 (2016–2017) 564 15.0Table 15.4.1 footnote E
(8.5–25.0)
<LOD <LOD Table footnote F 0.18
(0.12–0.24)
60–79 years
5 (2016–2017) 573 10.6
(7.8–14.3)
<LOD <LOD Table footnote F 0.19Table 15.4.1 footnote E
(0.080–0.31)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 0.018 μg/L.

References

15.5 Ethylbenzene

Ethylbenzene (CASRN 100-41-4) is a colourless liquid and a volatile organic compound (VOC). It is a high-production volume industrial chemical produced commercially primarily by alkylating benzene with ethylene (ATSDR, 2010; IARC, 2000). The quantity of ethylbenzene manufactured in Canada has remained relatively stable since 1999 (Environment and Climate Change Canada and Health Canada, 2016).

Major uses of ethylbenzene include manufacturing of styrene and synthetic rubber (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016; IARC, 2000). It is also used in the production of diethylbenzene, acetophenone, and other chemicals, as a solvent in the semiconductor industry, and as a general solvent used in manufactured products (ATSDR, 2010). Ethylbenzene is a constituent of asphalt, naphtha, and automotive and aviation fuels, including gasoline that typically contains about 2% ethylbenzene by weight (ATSDR, 2010). Commercial mixed xylenes contain ethylbenzene at levels of up to 25%; as such, ethylbenzene may be present in some paints, including spray paints and primers, lacquers, printing inks, insecticides, and solvents containing xylenes (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016; IARC, 2000).

Ethylbenzene is released to the environment, primarily to the atmosphere, from natural and anthropogenic sources. It has been measured in emissions from volcanoes, forest fires, crude petroleum, and coal deposits (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016; IARC, 2000). Anthropogenic sources include the manufacture, processing, storage, use, transportation and disposal of fuels, solvents, petrochemicals, and polymers. Releases of ethylbenzene to air, especially as a product of fuel combustion, may be increasing as well, with increasing population and demand for energy (Environment and Climate Change Canada and Health Canada, 2016).

For the general population, most exposure to ethylbenzene occurs through the inhalation of indoor air (Environment and Climate Change Canada and Health Canada, 2016; Health Canada, 2007). Inside residences, ethylbenzene levels in air have been shown to be higher for homes with attached garages, with a higher number of occupants, with recent renovations, and in which fragrances and paint remover have recently been used (Wheeler et al., 2013). Use of consumer products such as lacquers, stains, varnishes, and concrete floor sealers can also result in inhalation exposures of short duration but potentially high concentration. Although cigarette smoke may contribute to the concentration of ethylbenzene in the home, it is not likely to be a significant source (Environment and Climate Change Canada and Health Canada, 2016; Health Canada, 2010). Various other marketplace products containing ethylbenzene can also contribute to its presence in indoor air, such as caulking, building materials, and automotive products (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016). Outdoor air, drinking water, soil, and food are not considered to constitute major sources of exposure for the general population (Health Canada, 2007).

Ethylbenzene is readily absorbed and distributed throughout the body following inhalation, oral exposure, or dermal exposure (ATSDR, 2010; IARC, 2000). The proportion of ethylbenzene absorbed following inhalation is approximately 49% to 64% in humans (ATSDR, 2010). Once absorbed, ethylbenzene is eliminated from the blood and body mostly in the urine, with minor amounts exhaled in the breath, and has an elimination half-life ranging from less than one hour up to 25 hours (ATSDR, 2010). Following oral exposure, the proportion of absorbed ethylbenzene is approximately 72% to 92% in laboratory animals, with rapid elimination occurring predominantly via urinary excretion (ATSDR, 2010). In contrast, research suggests that following uptake through the skin, only a small proportion of absorbed ethylbenzene is eliminated in the urine and none in exhaled air (ATSDR, 2010). Ethylbenzene levels in blood are the most accurate biomarker of ethylbenzene exposure and are reflective of recent exposures (ATSDR, 2010).

In humans, ethylbenzene can be irritating to the eyes, nose, throat, lungs, and skin, and it has been associated with symptoms of headaches, dizziness, vertigo, and feelings of intoxication (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016). In general, acute inhalation exposure has been associated with reversible neurological symptoms and respiratory tract irritation. Chronic exposure has been associated with impaired neurological function, including cognitive and neuromuscular performance (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016). Studies in laboratory animals exposed by inhalation to ethylbenzene provide supporting evidence for central nervous system effects, neuromuscular and behavioural changes, and hearing loss (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016). In laboratory animals, chronic exposure to high levels of ethylbenzene in air and orally has been associated with kidney and liver damage, some minor developmental effects (such as decreased fetal body weight), and effects in blood, pituitary, thyroid, and respiratory tissues (ATSDR, 2010; Environment and Climate Change Canada and Health Canada, 2016). Ethylbenzene is classified as possibly carcinogenic to humans (Group 2B) according to the International Agency for Research on Cancer (IARC, 2000). However, the more recent evaluation by Health Canada and Environment Canada concludes that ethylbenzene is likely to be a threshold carcinogen, indicating that there is a threshold below which tumour formation would not be expected (Environment and Climate Change Canada and Health Canada, 2016).

The Government of Canada has conducted a science-based screening assessment under the Chemicals Management Plan to determine whether ethylbenzenepresents or may present a risk to the environment or human health as per the criteria set out in section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Environment and Climate Change Canada and Health Canada, 2016). The assessment concluded that ethylbenzene does not meet any of the criteria for being considered toxic under CEPA 1999 (Environment and Climate Change Canada and Health Canada, 2016). Ethylbenzene is part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013), as well as from on-road (Canada, 2003; Canada, 2015) and off-road (Canada, 2013; Canada, 2017) engines and vehicles.

Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, has developed a guideline for Canadian drinking water quality that establishes a maximum acceptable concentration for ethylbenzene that is protective of human health, as well as an aesthetic objective for ethylbenzene based on its odour threshold (Health Canada, 2014). The guideline is based on non-cancer effects in the liver and pituitary gland in experimental animals, and is considered to be protective of both cancer and non-cancer health effects (Health Canada, 2014).

Ethylbenzene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of ethylbenzene in blood can be an indicator of recent exposure to ethylbenzene and does not necessarily mean that an adverse health effect will occur.

Ethylbenzene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Statistics Canada, 2013; Wheeler et al., 2013; Zhu et al., 2013), cycle 3 (2012–2013) (Statistics Canada, 2015), and cycle 4 (2014–2015), and in tap water from households in cycles 3 and 4. Further details on the indoor air and tap water studies are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air and tap water data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.5.1: Ethylbenzene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.5.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2441 82.0
(74.4–87.7)
0.026
(0.020–0.033)
<LOD 0.025
(0.017–0.033)
0.084
(0.070–0.098)
0.12
(0.095–0.15)
4 (2014–2015) 2505 89.7
(83.1–93.9)
0.026
(0.022–0.031)
<LOD 0.024
(0.018–0.029)
0.078
(0.061–0.094)
0.11
(0.089–0.13)
5 (2016–2017) 2576 78.2
(67.4–86.1)
0.024
(0.019–0.030)
<LOD 0.023
(0.017–0.028)
0.083
(0.059–0.11)
0.12
(0.092–0.16)
Males, 12–79 years
3 (2012–2013) 1212 83.8
(77.9–88.4)
0.028
(0.022–0.034)
<LOD 0.026
(0.018–0.034)
0.088
(0.063–0.11)
0.14
(0.096–0.18)
4 (2014–2015) 1239 89.6
(82.7–93.9)
0.028
(0.023–0.035)
<LOD 0.027
(0.019–0.034)
0.088
(0.067–0.11)
0.12
(0.086–0.15)
5 (2016–2017) 1281 78.2
(68.8–85.4)
0.027
(0.022–0.033)
<LOD 0.026
(0.020–0.032)
0.10
(0.077–0.12)
0.13
(0.10–0.16)
Females, 12–79 years
3 (2012–2013) 1229 80.2
(70.1–87.5)
0.025
(0.018–0.033)
<LOD 0.025
(0.016–0.033)
0.080
(0.057–0.10)
0.11
(0.076–0.14)
4 (2014–2015) 1266 89.8
(83.1–94.1)
0.024
(0.020–0.029)
<LOD 0.022
(0.018–0.026)
0.065
(0.046–0.084)
0.093
(0.068–0.12)
5 (2016–2017) 1295 78.1
(63.5–88.0)
0.021
(0.016–0.028)
<LOD 0.019
(0.014–0.025)
0.064Table 15.5.1 footnote E
(0.033–0.095)
0.11Table 15.5.1 footnote E
(0.059–0.15)
12–19 years
3 (2012–2013) 731 78.6
(66.8–87.0)
0.020
(0.016–0.027)
<LOD 0.021
(0.015–0.027)
0.064
(0.044–0.084)
0.081
(0.056–0.11)
4 (2014–2015) 709 86.2
(75.4–92.7)
0.022
(0.017–0.027)
<LOD 0.022
(0.016–0.027)
0.053
(0.044–0.061)
0.065
(0.052–0.077)
5 (2016–2017) 835 69.7
(53.3–82.3)
0.018
(0.014–0.025)
<LOD 0.019
(0.014–0.024)
0.047
(0.032–0.062)
0.065Table 15.5.1 footnote E
(0.032–0.097)
20–39 years
3 (2012–2013) 532 80.6
(73.5–86.2)
0.026
(0.019–0.035)
<LOD 0.026Table 15.5.1 footnote E
(0.012–0.041)
0.077Table 15.5.1 footnote E
(0.040–0.11)
0.12Table 15.5.1 footnote E
(0.058–0.17)
4 (2014–2015) 596 88.7
(81.3–93.4)
0.024
(0.019–0.032)
<LOD 0.023
(0.016–0.029)
0.062Table 15.5.1 footnote E
(0.034–0.089)
Table footnote F
5 (2016–2017) 591 77.2
(59.9–88.4)
0.024
(0.018–0.032)
<LOD 0.023
(0.015–0.031)
0.079
(0.054–0.10)
0.11
(0.081–0.14)
40–59 years
3 (2012–2013) 591 84.7
(75.7–90.8)
0.029
(0.024–0.037)
<LOD 0.027
(0.020–0.034)
0.10
(0.082–0.12)
0.14
(0.10–0.18)
4 (2014–2015) 622 91.5
(82.2–96.1)
0.029
(0.023–0.036)
0.012Table 15.5.1 footnote E
(<LOD–0.016)
0.025
(0.017–0.033)
0.098
(0.070–0.13)
0.12
(0.10–0.14)
5 (2016–2017) 569 81.7
(71.0–89.1)
0.026
(0.020–0.033)
<LOD 0.024
(0.018–0.030)
0.097
(0.062–0.13)
0.13
(0.095–0.17)
60–79 years
3 (2012–2013) 587 81.6
(71.0–88.9)
0.025
(0.019–0.032)
<LOD 0.024
(0.016–0.032)
0.079
(0.064–0.094)
0.12Table 15.5.1 footnote E
(0.062–0.17)
4 (2014–2015) 578 90.2
(84.6–93.9)
0.027
(0.024–0.030)
<LOD 0.026
(0.022–0.029)
0.087
(0.074–0.10)
0.12
(0.084–0.15)
5 (2016–2017) 581 78.3
(70.0–84.8)
0.023
(0.019–0.028)
<LOD 0.021
(0.016–0.026)
0.083
(0.056–0.11)
0.12
(0.080–0.17)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.011, 0.011, and 0.013 μg/L, respectively.

References

15.6 Isopropylbenzene

Isopropylbenzene (CASRN 98-82-8), also known as cumene, is a colourless liquid that is classified as a volatile organic compound (VOC) (IARC, 2013; WHO, 2005). It is a natural constituent of crude oil and can be found in plants and food. Commercially, isopropylbenzene can be produced via distillation of coal tar and petroleum or alkylation of benzene with propene (Environment and Climate Change Canada and Health Canada, 2019; IARC, 2013). As a component of finished fuel, isopropylbenzene can be found in gasoline blends and high-octane aviation fuel.

Isopropylbenzene is used as an intermediate for chemical production, mostly for the manufacture of acetone and phenol (European Commission, 2016). It is also used in printing, ore mining, the manufacture of plastic, rubber, pesticides and pharmaceuticals, and as a solvent for fat or resin. It is also used in several consumer products, such as automotive-related products, adhesives, lubricants, specialty cleaning products, and paints (Environment and Climate Change Canada and Health Canada, 2019; EPA, 1997; IARC, 2013; NTP, 2013; WHO, 2005).

Isopropylbenzene is released to the environment mainly from the use, manufacture, and transport of processed hydrocarbon fuel. Primary anthropogenic sources include release from petrochemical refineries, accidental petroleum spills, and evaporation and combustion of petroleum products from petrol stations and motor vehicles. Other anthropogenic sources include release from products containing isopropylbenzene, tobacco smoke, jet engine exhaust, and several industrial processes (EPA, 1997; IARC, 2013; WHO, 2005).

The primary route of human exposure to isopropylbenzene is inhalation (Environment and Climate Change Canada and Health Canada, 2019; IARC, 2013). Exposure in air accounts for an estimated 97% of total isopropylbenzene intake for Canadians (Environment and Climate Change Canada and Health Canada, 2019). In Canada, levels of isopropylbenzene measured in indoor air are generally low, but are higher than those detected in outdoor air (Environment and Climate Change Canada and Health Canada, 2019; Health Canada, 2010a; Health Canada, 2010b; Health Canada, 2012; Health Canada, 2013). Various building materials and stored combustion equipment can contribute to the presence of isopropylbenzene in indoor air (Won et al., 2013; Won et al. 2014; Won et al., 2015). Given the volatility of isopropylbenzene, inhalation as well as dermal exposures may result from the use of products available to consumers (Environment and Climate Change Canada and Health Canada, 2019; HSDB, 2013). To a lesser extent, exposure may also occur from the ingestion of food or water. Although isopropylbenzene has been monitored in drinking water in three Canadian cities since 2000, no detectable levels have been found (Environment and Climate Change Canada and Health Canada, 2019).

Human studies show that isopropylbenzene is readily absorbed following inhalation exposure. This finding is supported by experimental animal studies demonstrating rapid absorption following exposure by inhalation, ingestion, or dermal contact (EPA, 1997; NTP, 2013). Animal studies demonstrate that isopropylbenzene is widely distributed throughout the body following absorption, with higher concentrations found in adipose tissue, bones, liver, and kidneys (EPA, 1997). Isopropylbenzene is highly lipophilic and can potentially accumulate in adipose tissue (European Commission, 2016). It is extensively metabolized in the body by hepatic and extrahepatic tissues, including the lungs, to water soluble compounds (NTP, 2013; WHO, 2005). Several metabolites of isopropylbenzene were detected in animal experiments, the main one being 2-phenyl-2-propanol, which is also detected in human studies (NTP, 2013). Different elimination half-lives have been estimated for humans, with the average being less than a day. Isopropylbenzene is rapidly eliminated from the body, principally as a conjugate of 2-phenyl-2-propanol. Experimental studies show that isopropylbenzene is excreted mainly in urine (>70%), and to a lesser extent in feces or exhaled air (NTP, 2013; WHO, 2005). The parent chemical in blood or exhaled air, as well as the urinary level of its main metabolite, 2-phenyl-2-propanol, can be used as biomarkers of exposure (European Commission, 2016).

Although the acute systemic toxicity of isopropylbenzene is regarded as generally low, this substance has been shown to cause dizziness, slight incoordination, and unconsciousness in humans following exposure to high levels through inhalation (HSDB, 2013). In laboratory animals, central nervous system depression and transient ataxia have been observed following high-level exposure (Environment and Climate Change Canada and Health Canada, 2019; HSDB, 2013; Jahnke et al., 2013). Human and laboratory animal studies both report low to moderate toxicity from oral administration of isopropylbenzene. Irritation has been observed after dermal or eye contact (European Commission, 2016; HSDB, 2013; Jahnke et al., 2013). Chronic inhalation exposure has been found to lead to increased liver, kidney, and adrenal weights in laboratory animals (European Commission, 2016). Chronic inhalation exposure is also associated with tumours of the respiratory tract, kidneys, liver, and spleen in laboratory animals; however, there is a lack of human data on the carcinogenicity of isopropylbenzene (IARC, 2013; NTP, 2013). The International Agency for Research on Cancer (IARC) has classified isopropylbenzene and one of its metabolites (α-methylstyrene) as possibly carcinogenic to humans (Group 2B) based on sufficient evidence of carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 2013).

The Government of Canada has conducted a science-based screening assessment under the Chemicals Management Plan to determine whether isopropylbenzene presents or may present a risk to the environment or human health as per the criteria set out in section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Environment and Climate Change Canada and Health Canada, 2019). The assessment concluded that isopropylbenzene does not meet any of the criteria for being considered toxic under CEPA 1999 (Environment and Climate Change Canada and Health Canada, 2019).

In 2017, Health Canada published an Indoor Air Reference Level (IARL) for isopropylbenzene (EPA, 1997; Health Canada, 2017). Isopropylbenzene is part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013).

Isopropylbenzene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 5 (2016–2017). Data are presented as μg/L blood. Finding a measurable amount of isopropylbenzene in blood can be an indicator of recent exposure to isopropylbenzene and does not necessarily mean that an adverse health effect will occur.

Isopropylbenzene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013), cycle 3 (2012–2013), and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.6.1: Isopropylbenzene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.6.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2571 70.1
(56.7–80.8)
0.015
(0.011–0.021)
<LOD 0.016
(0.010–0.022)
0.044Table 15.6.1 footnote E
(0.021–0.067)
0.068Table 15.6.1 footnote E
(0.031–0.10)
Males, 12–79 years
5 (2016–2017) 1280 65.7
(47.9–80.0)
0.014Table 15.6.1 footnote E
(<LOD–0.021)
<LOD 0.015Table 15.6.1 footnote E
(<LOD–0.021)
0.044Table 15.6.1 footnote E
(0.014–0.075)
0.071Table 15.6.1 footnote E
(0.039–0.10)
Females, 12–79 years
5 (2016–2017) 1291 74.5
(63.6–83.0)
0.016
(0.012–0.021)
<LOD 0.017
(0.011–0.023)
0.043Table 15.6.1 footnote E
(0.026–0.060)
0.060Table 15.6.1 footnote E
(0.016–0.10)
12–19 years
5 (2016–2017) 833 68.6
(56.2–78.8)
0.014
(0.010–0.019)
<LOD 0.015
(0.012–0.019)
0.037Table 15.6.1 footnote E
(0.012–0.063)
Table footnote F
20–39 years
5 (2016–2017) 590 64.4
(51.8–75.4)
0.013
(<LOD–0.019)
<LOD 0.014Table 15.6.1 footnote E
(<LOD–0.020)
Table footnote F 0.075Table 15.6.1 footnote E
(0.031–0.12)
40–59 years
5 (2016–2017) 569 72.0
(54.2–84.8)
0.016Table 15.6.1 footnote E
(0.011–0.023)
<LOD 0.017Table 15.6.1 footnote E
(0.010–0.025)
0.043Table 15.6.1 footnote E
(0.025–0.061)
Table footnote F
60–79 years
5 (2016–2017) 579 76.3
(62.5–86.2)
0.017
(0.012–0.024)
<LOD 0.017Table 15.6.1 footnote E
(0.011–0.024)
0.051Table 15.6.1 footnote E
(0.030–0.072)
0.074Table 15.6.1 footnote E
(0.031–0.12)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 0.010 μg/L.

References

15.7 Methyl isobutyl ketone

Methyl isobutyl ketone (MIBK) (CASRN 108-10-1), also known as 4-methyl-2-pentanone, among other synonyms, belongs to the ketone class of organic compounds and takes the form of a clear colourless liquid with an odour described as pleasant. MIBK can occur naturally in foods (e.g., fruit, olive oil, chicken, eggs, beer, coffee, and cow's milk) or as a flavouring ingredient in food items, such as baked goods, frozen dairy products, gelatins/puddings, meat products, and soft candy (Environment and Climate Change Canada and Health Canada, 2019; IARC, 2013). MIBK is also a high-production volume industrial chemical that is most commonly synthesized by aldol condensation of acetone and its derivative intermediates, diacetone alcohol and mesityl oxide (IARC, 2013). MIBK is used as an industrial organic solvent for gums, resins, paints, varnishes, lacquers, and nitrocellulose (NCBI, 2018). It may also be used as a denaturant, chemical intermediate, bulking agent in drugs, food-flavouring agent, and as a component of food-packaging materials (IARC, 2013; OECD, 2009; OEHHA, 2018).

MIBK enters the environment primarily from anthropogenic sources. It can be released into the atmosphere during its production through fugitive emissions and the incomplete removal of vapours from reaction gases (IARC, 2013; OECD, 2009). It may also leak from landfills or be released to surface waters during the discharge of spent scrubbing water from industrial production processes (IARC, 2013).

The most likely routes of exposure to MIBK are the ingestion of contaminated drinking water and inhalation or dermal exposure from the use of consumer products (Environment and Climate Change Canada and Health Canada, 2019; IARC, 2013). Concentrations of MIBK are higher in indoor air than in outdoor air in Canadian homes (Health Canada, 2010a; Health Canada 2010b; Health Canada, 2012; Health Canada, 2013). MIBK is found in and/or emitted by products such as building materials, pesticides, automotive products, and agents for wax/oil separation, leather finishing, and textile coating (EPA, 2003; IARC, 2013; Won et al., 2013; Won et al., 2014; Won et al. 2015; Won and Yang, 2012). Exposure can also occur through the ingestion of food that contains MIBK as a natural constituent, as a flavouring agent, or from its migration from food packaging (Environment and Climate Change Canada and Health Canada, 2019; IARC, 2013). MIBK has been shown to be readily biodegradable and will likely volatilize rapidly from water or soil; therefore, it is not expected to persist in the environment (OECD, 2009).

Toxicokinetic studies demonstrate that MIBK is readily absorbed into the blood following exposure by any route, and that its level in blood is related to the oral or inhalation exposure level (EPA, 2003). MIBK can be found as a volatile component of urine, and its presence in urine also serves as a biological marker of exposure (NCBI, 2018). Data from human studies show that following absorption, MIBK can be distributed throughout the body to tissues that include the liver, kidney, lung, and brain; it is rapidly eliminated from the blood following cessation of exposure (generally within two hours), with exhalation being the major route of elimination (IARC, 2013). Experimental animal data indicate that major metabolites of MIBK include diacetone alcohol, 4-hydroxymethyl isobutyl ketone, and 4-methyl-2-pentanol, and that the metabolic pathway likely involves alcohol dehydrogenase and cytochrome P450 mono-oxygenases (IARC, 2013). MIBK has been detected in breast milk; evidence from one human study suggests that MIBK can enter the umbilical cord and cross the placenta (Environment and Climate Change Canada and Health Canada, 2019; IARC, 2013).

Acute exposure to MIBK in humans has been shown to irritate the eyes and mucous membranes, and produce effects on the central nervous system such as headache, weakness, nausea, light-headedness, lack of coordination, irritation, and narcosis (NCBI, 2018; OECD, 2009). Similar effects have been observed in occupational studies of long-term human exposure to MIBK, along with insomnia, intestinal pain, and slight enlargement of the liver (NCBI, 2018). Increased liver and kidney weights, reversible kidney damage and lethargy have been noted in chronic studies with laboratory animals following repeated inhalation or oral exposures to high concentrations of MIBK (NCBI, 2018; OECD, 2009). MIBK may produce its effects by disrupting nerve membrane integrity, which could potentially explain the transient neurological symptoms in humans and animals that occur only during or immediately following exposure (EPA, 2003). Maternal toxicity (e.g., increased liver and kidney weights) and fetotoxicity (e.g., reduced fetal body weights and delayed ossification) have been observed at high exposure concentrations in animal studies (OECD, 2009). The International Agency for Research on Cancer (IARC) has classified MIBK as possibly carcinogenic to humans (Group 2B) based on sufficient evidence of carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 2013).

The Government of Canada has conducted a science-based screening assessment under the Chemicals Management Plan to determine whether MIBK presents or may present a risk to the environment or human health as per the criteria set out in section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Environment and Climate Change Canada and Health Canada, 2019). The assessment proposes to conclude that MIBK is toxic under CEPA 1999, as it is considered harmful to human health (Environment and Climate Change Canada and Health Canada, 2019).

In 2017, Health Canada published an Indoor Air Reference Level (IARL) for MIBK (Health Canada, 2017). MIBK is part of a larger class of volatile organic compounds (VOCs) that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013). Environment Canada identified MIBK as a substance of concern that may be found in screen-printing and digital imaging processes. It is also part of an environmental performance agreement that involves targeted VOC emissions reductions by participating facilities (Environment Canada, 2012). MIBK is listed on Health Canada's Natural Health Products Ingredients Database as having a non-medicinal role for oral use as a flavour enhancer or topical use as a denaturant (Health Canada, 2018a). Health Canada recently implemented the International Council for Harmonisation Guidelines for Residual Solvents, which places MIBK in Class 2 (solvents to be limited) (Health Canada, 2018b).

MIBK was analyzed in the whole blood of Canadian Health Measure Survey (CHMS) participants aged 12–79 years in cycle 5 (2016–2017). Data are presented in blood as µg/L. Finding a measurable amount of MIBK in blood is an indicator of exposure to MIBK and does not necessarily mean that an adverse health effect will occur.

MIBK was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013), cycle 3 (2012–2013), and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.7.1: Methyl isobutyl ketone — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.7.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2363 73.4
(61.9–82.5)
0.040
(0.033–0.049)
<LOD 0.043
(0.035–0.051)
0.094
(0.072–0.12)
0.12
(0.084–0.15)
Males, 12–79 years
5 (2016–2017) 1166 74.1
(63.1–82.7)
0.041
(0.033–0.051)
<LOD 0.043
(0.035–0.050)
0.11
(0.077–0.13)
0.13Table 15.7.1 footnote E
(0.050–0.22)
Females, 12–79 years
5 (2016–2017) 1197 72.8
(59.7–82.9)
0.039
(0.032–0.048)
<LOD 0.043
(0.034–0.052)
0.085
(0.070–0.10)
0.10
(0.080–0.13)
12–19 years
5 (2016–2017) 767 63.8
(48.8–76.5)
0.032
(<LOD–0.039)
<LOD 0.034
(<LOD–0.042)
0.066
(0.049–0.083)
0.088
(0.066–0.11)
20–39 years
5 (2016–2017) 533 68.1
(54.5–79.2)
0.037
(0.030–0.047)
<LOD 0.042
(0.033–0.050)
0.090
(0.058–0.12)
0.12Table 15.7.1 footnote E
(0.043–0.20)
40–59 years
5 (2016–2017) 519 77.6
(63.2–87.4)
0.041
(0.033–0.052)
<LOD 0.043
(0.033–0.054)
0.092
(0.067–0.12)
0.11
(0.087–0.14)
60–79 years
5 (2016–2017) 544 79.3
(63.7–89.3)
0.047
(0.037–0.060)
<LOD 0.051
(0.040–0.062)
0.11
(0.086–0.13)
0.14
(0.10–0.18)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 0.029 μg/L.

References

15.8 Nitrobenzene

Nitrobenzene (CASRN 98-95-3) is a nitroaromatic substance that is a greenish-yellow to yellow oily liquid at room temperature, with an odour similar to bitter almonds or shoe polish (NTP, 2016). Nitrobenzene is a high-production volume chemical generally produced industrially in a batch-wise or continuous nitration process in which mixed acid is added to an excess of benzene under temperature-controlled conditions (Booth, 2012; EPA, 2009).

The major use of nitrobenzene is as an intermediate in the production of aniline, a chemical that is used to produce diphenylmethane and diisocyanate (MDI) for polyurethane foams (CAREX, 2018; NTP, 2016). It also has a number of minor uses, including as a solvent (e.g., in petroleum refining or in gun cleaners), an ingredient of metal polishes and soaps, and in the manufacture of rubber chemicals, herbicides, dyes, pigments, fibres, and other chemicals (CAREX, 2018; NICNAS, 2016).

Nitrobenzene is not known to occur naturally (CAREX, 2018). It may be present in groundwater, surface water, and air, but concentrations are generally low and below detection limits (WHO, 2009). Nitrobenzene in ambient air may originate from industrial processes (e.g., manufacturing facilities and petroleum refineries), abandoned hazardous waste sites, or from the atmospheric photochemical reaction of nitrous oxides and benzene from automobile exhaust; however, most nitrobenzene produced during its manufacture is retained in closed systems. Restrictions on benzenes in gasoline have reduced levels of nitrobenzene in the atmosphere in Canada (CAREX, 2018). Levels of nitrobenzene in air, ground water, soil, and plant tissues may be higher around abandoned hazardous waste sites. Data indicate that levels in groundwater are expected to be higher than in surface waters, likely due to the limited potential for volatilization and biodegradation in groundwater systems (WHO, 2009).

Exposure of the Canadian general population to nitrobenzene from air, water, and soil and from the use of consumer products is expected to be negligible (Environment and Climate Change Canada and Health Canada, 2016). Populations in the vicinity of petroleum refineries, abandoned hazardous waste sites, and certain manufacturing activities could potentially have elevated exposures to nitrobenzene.

Nitrobenzene is readily absorbed following exposure, with estimated uptake rates ranging from 73% to 87% in human volunteers following inhalation and 43% to 69% in animals following oral exposure (NICNAS, 2016). Nitrobenzene has been shown to distribute primarily to erythrocytes, spleen, liver, testes, and brain tissue following absorption (NICNAS, 2016). Based on animal studies, there are three major metabolic pathways for nitrobenzene: a two-step reduction to aniline by intestinal microflora, a six-step reduction to aniline in hepatic microsomes and erythrocytes, and oxidative metabolism by hepatic microsomes to nitrophenols (likely involving cytochrome P450s) (EPA, 2009; NICNAS, 2016). Nitrobenzene is excreted mainly in urine, and to a lesser extent in feces and expired air, in both animals and humans (EPA, 2009; NICNAS, 2016). In humans, about 70% of orally dosed nitrobenzene was found to be eliminated from the body within the course of a week, with about 58% of the dose eliminated as metabolites in urine and 9% in feces, with a small fraction in expired air (~1%). The elimination half-life of nitrobenzene in urine — based on a small number of studies in humans and different routes of exposure — was estimated to range from 20 hours to a few days (IARC, 1996). A major portion of the absorbed dose is excreted into urine as 4-nitrophenol, with a smaller fraction excreted as 4-aminophenol or 3-nitrophenol. Studies suggest that the portion of absorbed nitrobenzene not eliminated from the body may bind to hemoglobin and plasma proteins (EPA, 2009).

In humans, acute exposure to nitrobenzene can potentially lead to respiratory depression, general weakness, severe headaches and dizziness, vomiting, convulsions, and unconsciousness (NICNAS, 2016). The characteristic symptom of acute exposure in humans is methemoglobinemia, coupled with cyanosis (EPA, 2009; NICNAS, 2016). Other reported acute systemic effects in humans include the formation of Heinz bodies in erythrocytes, effects on the bone marrow and lymphoid organs, neurotoxicity, and hepatotoxicity (NICNAS, 2016). Studies in animals demonstrate a wide spectrum of non-cancer effects following sub-chronic or chronic exposure to nitrobenzene, including increased organ weights and histopathologic lesions of the spleen, liver, adrenals, kidney, and brain, methemoglobinemia with subsequent hemolytic anemia and splenic congestion, neurotoxicity, and a significant and pronounced adverse effect on the male reproductive system resulting in reduced fertility (EPA, 2009; NICNAS, 2016). In addition, long-term inhalation exposure has been reported to result in olfactory degeneration and bronchiolization of the alveoli in laboratory animals (EPA, 2009). Increased incidences of non-neoplastic lesions have been observed in the lung, thyroid, liver, kidney, spleen, nasal turbinates, and testes of chronically exposed animals at both low and high doses, with the severity of effect increasing with dose (EPA, 2009; NICNAS, 2016). Nitrobenzene is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B) based on sufficient evidence of carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 1996).

The Government of Canada has conducted a rapid screening assessment under the Chemicals Management Plan to determine whether nitrobenzene presents or may present a risk to the environment or human health as per the criteria set out in section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Environment and Climate Change Canada and Health Canada, 2016). The assessment concluded that nitrobenzene does not meet any of the criteria for being considered toxic under CEPA 1999 based on current use patterns and quantities in commerce in Canada being unlikely to cause harm to the environment or human health (Environment and Climate Change Canada and Health Canada, 2016). However, nitrobenzene was recommended as a potential candidate for a significant new activity notice (SNAc) under CEPA 1999 on the basis of classifications for health effects of concern (carcinogenicity and reproductive effects) by other national or international agencies (Environment and Climate Change Canada and Health Canada, 2016).

Nitrobenzene is identified as being prohibited on the List of Prohibited and Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient Hotlist or simply the Hotlist), an administrative tool that Health Canada uses to communicate to manufacturers and others that certain substances, when present in a cosmetic, may not be compliant with requirements of the Food and Drugs Act or the Cosmetic Regulations (Health Canada, 2018).

Nitrobenzene is also part of a larger class of volatile organic compounds (VOCs) that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has taken and proposed a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013).

Nitrobenzene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 in cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of nitrobenzene in blood can be an indicator of a recent exposure to nitrobenzene and does not necessarily mean that an adverse health effect will occur.

Table 15.8.1: Nitrobenzene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.8.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2327 Table footnote F <LOD <LOD <LOD <LOD
Males, 12–79 years
5 (2016–2017) 1164 Table footnote F <LOD <LOD <LOD <LOD
Females, 12–79 years
5 (2016–2017) 1163 Table footnote F <LOD <LOD <LOD <LOD
12–19 years
5 (2016–2017) 753 0 <LOD <LOD <LOD <LOD
20–39 years
5 (2016–2017) 539 Table footnote F <LOD <LOD <LOD <LOD
40–59 years
5 (2016–2017) 523 Table footnote F <LOD <LOD <LOD <LOD
60–79 years
5 (2016–2017) 512 0 <LOD <LOD <LOD <LOD

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 1.1 μg/L.

References

15.9 Styrene

Styrene (CASRN 100-42-5) is a colourless liquid classified as a volatile organic compound (VOC) and a high-production volume industrial chemical. Styrene was first recovered by distillation of a natural resin (storax balsam), sapwood, and bark tissues of trees (ATSDR, 2010; IARC, 2002).

Styrene has been synthetically produced since the early 19th century and is a well-known impurity of coal-tar industrial processing and petroleum cracking (IARC, 2002). Styrene is available as a commercial product and is used worldwide in the manufacture of plastics, glass fibre-reinforced resins, protective coatings, ion-exchange resins, and synthetic rubber (ATSDR, 2010; IARC, 2002). Commercial styrene can contain traces of other components, including benzene, ethylbenzene, xylene, and other VOCs (IARC, 2002). In Canada, industrial uses of styrene include the manufacture of polystyrene, styrene-butadiene latex and rubber, acrylonitrile-butadiene styrene resins, and unsaturated polyester resins (Environment Canada and Health Canada, 1993). Styrene-based polymer materials are used in the manufacture of a wide range of products, most of which also contain a small amount of unlinked styrene monomer (ATSDR, 2010; Environment Canada and Health Canada, 1993). Examples of products made with or containing styrene include foam insulation, automobile tires, packaging materials, custom mouldings, waxes and surface coatings, adhesives, and metal cleaners (ATSDR, 2010; Environment Canada and Health Canada, 1993).

Styrene is released to the environment from natural and anthropogenic sources. Styrene releases to the environment are mainly atmospheric and occur as a result of the manufacture, use, and disposal of styrene-containing products, industrial releases, vehicle exhaust, incineration, and tobacco smoke (Environment Canada and Health Canada, 1993; ATSDR, 2010). Production, use, and disposal of styrene and styrene-containing products can also result in releases to the aquatic environment via wastewater. Natural sources of styrene releases to the environment include biodegradation of vegetation and organic material (ATSDR, 2010; Environment Canada and Health Canada, 1993).

The most common route of exposure to styrene in the general population is inhalation, with levels of styrene often higher in indoor air than outdoor (Health Canada, 2010a; Health Canada, 2010b; Health Canada, 2012; Health Canada, 2013; ATSDR, 2010; Environment Canada and Health Canada, 1993). Styrene is a minor and natural component of tobacco smoke, and tobacco smoke is the major contributor to the total styrene exposure in smokers (Environment Canada and Health Canada, 1993; Zhu et al., 2013). In addition to tobacco smoke, common sources of styrene present in air are automobile exhaust, the use and manufacturing of styrene, and the use of photocopiers and laser printers (ATSDR, 2010; Environment Canada and Health Canada, 1993). Sources of styrene in indoor air include stored combustion equipment, various building materials, furniture, air fresheners, shampoo, incense, candles and mothballs (Won et al., 2013; Won et al., 2014; Won and Lusztyk, 2011; Won and Yang, 2012). Additional exposures in the general population may occur through ingestion of food and beverages; however, most styrene associated with food is residue of styrene monomer leached from food packaged in polystyrene containers (ATSDR, 2010; Genualdi et al., 2014). Intake of styrene from drinking water is generally negligible (Environment Canada and Health Canada, 1993). Exposure through skin and eye contact can also occur when handling liquid styrene-containing products.

Styrene is readily absorbed and distributed throughout the body following inhalation, with the highest concentrations measured in adipose tissue (ATSDR, 2010; Environment Canada and Health Canada, 1993). In one study of laboratory animals, styrene absorption following oral exposure was rapid and complete followed by distribution to the kidney, liver, pancreas, adipose tissue, and, to a lesser extent, the stomach and small and large intestines (ATSDR, 2010). The absorbed styrene was rapidly eliminated from all tissues within one to three days. In a study with human volunteers, half-lives for the concentration of styrene in blood were estimated to range between one and 13 hours depending on the phase of elimination; in adipose tissue, an elimination half-life of two to five days was estimated (ATSDR, 2010). In humans, approximately 97% of the styrene absorbed is excreted as urinary metabolites, with the remainder eliminated unchanged in expired air (ATSDR, 2010; Environment Canada and Health Canada, 1993). The primary intermediate metabolite of styrene is styrene-7, 8-oxide, which is hydrolyzed to styrene glycol and further metabolized to mandelic and phenylglyoxylic acids, the principal urinary metabolites (ATSDR, 2010; Environment Canada and Health Canada, 1993). The major site of styrene metabolism is the liver. At high exposures that saturate metabolic enzymes, increased amounts of unchanged styrene are excreted in expired air (ATSDR, 2010; Environment Canada and Health Canada, 1993). In orally exposed laboratory animals, styrene was rapidly excreted in urine, with 90% eliminated within 24 hours, and less than 2% eliminated in feces (ATSDR, 2010). The most reliable biomarker of recent exposure to styrene is measurement of styrene in blood, urine, and breath (ATSDR, 2010).

Acute exposure to styrene is irritating to the eyes, nose, and throat, and induces dermatitis (ATSDR, 2010; IARC, 2002). In humans, acute exposure to high levels of styrene in air is associated with central nervous system effects, including nausea, headache, tiredness, and concentration problems, similar to the narcotic effects of other organic solvents; effects are generally reversible after the source of exposure is eliminated (ATSDR, 2010; Environment Canada and Health Canada, 1993). Chronic exposure to styrene is associated with central and peripheral nervous system effects, slower reaction times, decreased colour discrimination, hearing problems, altered hand-eye coordination, and impairment of verbal learning skills (ATSDR, 2010; ATSDR, 2012; IARC, 2002). Whether chronic styrene exposure results in permanent damage to the nervous system in humans has not been determined (ATSDR, 2010). Data from studies in humans and laboratory animals exposed via inhalation and the oral route to high levels of styrene also suggest styrene can be immunosuppressive (ATSDR, 2010; Environment Canada and Health Canada, 1993; IARC, 2002). Chronic exposure to high levels of styrene in air in the presence of other chemicals, including carcinogens, has been weakly associated with lymphomas and other cancers and chromosomal alterations (ATSDR, 2010; IARC, 2002). Styrene has been classified as possibly carcinogenic to humans, on the basis of limited evidence in animals and humans, by Environment Canada and Health Canada (Group III) and the International Agency for Research on Cancer (IARC; Group 2B) (Environment Canada and Health Canada, 1993; IARC, 2002). The styrene primary intermediate metabolite styrene-7, 8-oxide is classified by IARC as a Group 2A carcinogen, probably carcinogenic to humans (IARC, 2002).

Health Canada and Environment Canada concluded that levels of styrene normally found in the Canadian environment are not a concern to human health (Environment Canada and Health Canada, 1993). In 2017, Health Canada published an Indoor Air Reference Level (IARL) for styrene (Health Canada, 2017). Styrene is part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013). Because styrene has not been detected in Canadian drinking water supplies, no guideline for Canadian drinking water quality has been established by the Federal-Provincial-Territorial Committee on Drinking Water.

Styrene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of styrene in blood can be an indicator of exposure to styrene and does not necessarily mean that an adverse health effect will occur.

Styrene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013), cycle 3 (2012–2013), and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.9.1: Styrene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.9.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2063 91.4
(74.1–97.5)
0.043Table 15.9.1 footnote E
(0.029–0.062)
Table footnote F 0.043
(0.030–0.055)
0.12
(0.076–0.16)
0.17Table 15.9.1 footnote E
(0.10–0.23)
4 (2014–2015) 2527 96.2
(87.1–99.0)
0.055
(0.043–0.070)
0.026Table 15.9.1 footnote E
(0.013–0.040)
0.058
(0.047–0.069)
0.11
(0.094–0.13)
0.14
(0.12–0.15)
5 (2016–2017) 2527 89.1
(84.7–92.4)
0.027
(0.024–0.030)
<LOD 0.028
(0.024–0.032)
0.067
(0.054–0.079)
0.094
(0.075–0.11)
Males, 12–79 years
3 (2012–2013) 1036 91.7
(75.1–97.6)
0.043Table 15.9.1 footnote E
(0.029–0.064)
Table footnote F 0.045
(0.033–0.057)
0.12
(0.079–0.15)
0.17Table 15.9.1 footnote E
(0.099–0.24)
4 (2014–2015) 1251 95.0
(82.0–98.8)
0.056
(0.042–0.075)
0.026Table 15.9.1 footnote E
(<LOD–0.042)
0.063
(0.049–0.077)
0.12
(0.097–0.14)
0.14
(0.12–0.16)
5 (2016–2017) 1256 88.3
(80.8–93.1)
0.028
(0.025–0.033)
<LOD 0.029
(0.026–0.033)
0.074
(0.056–0.093)
0.099
(0.068–0.13)
Females, 12–79 years
3 (2012–2013) 1027 91.1
(72.6–97.5)
0.042Table 15.9.1 footnote E
(0.028–0.061)
Table footnote F 0.041
(0.028–0.055)
0.11Table 15.9.1 footnote E
(0.062–0.17)
0.16Table 15.9.1 footnote E
(0.092–0.23)
4 (2014–2015) 1276 97.4
(91.8–99.2)
0.053
(0.044–0.065)
0.027Table 15.9.1 footnote E
(0.015–0.038)
0.055
(0.046–0.065)
0.10
(0.078–0.12)
0.13
(0.10–0.15)
5 (2016–2017) 1271 90.0
(86.3–92.7)
0.026
(0.022–0.030)
<LOD 0.026
(0.021–0.031)
0.062
(0.049–0.074)
0.087
(0.060–0.11)
12–19 years
3 (2012–2013) 626 91.8
(73.0–97.9)
0.037Table 15.9.1 footnote E
(0.024–0.057)
Table footnote F 0.040
(0.029–0.052)
0.094Table 15.9.1 footnote E
(0.029–0.16)
0.15Table 15.9.1 footnote E
(0.063–0.24)
4 (2014–2015) 713 97.1
(86.5–99.4)
0.053
(0.041–0.068)
0.027Table 15.9.1 footnote E
(0.014–0.041)
0.058
(0.045–0.070)
0.097
(0.086–0.11)
0.10
(0.087–0.11)
5 (2016–2017) 824 90.5
(86.1–93.7)
0.025
(0.022–0.030)
<LOD 0.027
(0.022–0.031)
0.053
(0.044–0.063)
0.066
(0.048–0.085)
20–39 years
3 (2012–2013) 435 89.8
(69.4–97.2)
0.043Table 15.9.1 footnote E
(0.029–0.065)
<LOD 0.043Table 15.9.1 footnote E
(0.024–0.061)
0.12Table 15.9.1 footnote E
(0.055–0.18)
0.18Table 15.9.1 footnote E
(0.10–0.26)
4 (2014–2015) 600 97.0
(86.2–99.4)
0.055
(0.043–0.070)
0.029Table 15.9.1 footnote E
(0.014–0.044)
0.057
(0.047–0.068)
0.11
(0.085–0.13)
0.12
(0.10–0.15)
5 (2016–2017) 574 88.1
(79.1–93.6)
0.027
(0.023–0.032)
<LOD 0.027
(0.021–0.034)
0.072
(0.051–0.094)
0.095
(0.073–0.12)
40–59 years
3 (2012–2013) 493 93.5
(76.8–98.4)
0.045Table 15.9.1 footnote E
(0.031–0.066)
0.016Table 15.9.1 footnote E
(<LOD–0.026)
0.044
(0.032–0.056)
0.13
(0.090–0.16)
0.18Table 15.9.1 footnote E
(0.11–0.25)
4 (2014–2015) 625 94.0
(80.9–98.3)
0.056
(0.042–0.075)
0.025Table 15.9.1 footnote E
(<LOD–0.040)
0.064
(0.049–0.079)
0.12
(0.099–0.15)
0.15
(0.12–0.17)
5 (2016–2017) 555 88.6
(82.9–92.5)
0.028
(0.025–0.032)
<LOD 0.029
(0.025–0.033)
0.067
(0.053–0.080)
0.11Table 15.9.1 footnote E
(0.067–0.15)
60–79 years
3 (2012–2013) 509 90.2
(70.4–97.3)
0.041Table 15.9.1 footnote E
(0.027–0.063)
Table footnote F 0.044
(0.029–0.058)
0.11
(0.069–0.15)
0.14Table 15.9.1 footnote E
(0.049–0.24)
4 (2014–2015) 589 98.0
(94.5–99.3)
0.053
(0.043–0.065)
0.025Table 15.9.1 footnote E
(0.012–0.038)
0.053
(0.042–0.064)
0.11
(0.086–0.13)
0.14
(0.11–0.17)
5 (2016–2017) 574 90.7
(85.3–94.2)
0.026
(0.023–0.031)
0.011Table 15.9.1 footnote E
(<LOD–0.016)
0.027
(0.022–0.033)
0.062
(0.041–0.083)
0.092
(0.069–0.12)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.012, 0.012, and 0.011 μg/L, respectively.

References

15.10 1,1,1,2-Tetrachloroethane

1,1,1,2-Tetrachloroethane (CASRN 630-20-6) is a halogenated organic compound that is a colourless liquid at room temperature. It can be synthesized in a highly purified form by isomerization of 1,1,2,2-tetrachloroethane or by chlorination of 1,1-dichloroethylene, but it is also a by-product of the manufacture of other chlorinated ethanes (1,1,1-trichloroethane, 1,1,2-trichloroethane and 1,1,2,2-tetrachloroethane) (IARC, 2014). 1,1,1,2-Tetrachloroethane is not as widely studied as its isomer, 1,1,2,2-tetrachloroethane. However, this chemical summary will focus on the available information for 1,1,1,2-tetrachloroethane.

1,1,1,2-Tetrachloroethane is primarily used in the production of solvents such as trichloroethylene. It is also used as a laboratory reagent and as a solvent in the manufacture of bleaches, paint varnishes, insecticides, herbicides, and soil fumigants (IARC 2014). 1,1,1,2-Tetrachloroethane does not occur naturally. It is only released into the environment from anthropogenic sources (IARC, 2014). It can enter air through industrial air emissions and water through industrial waste streams (IARC, 2014). The general population may be exposed through inhalation of ambient air. Ingestion and skin or eye contact are other possible routes of exposure (Pohanish, 2012).

No data are available for the toxicokinetics of 1,1,1,2-tetrachloroethane in humans (IARC, 2014). In vitro pharmacokinetic data indicate that 1,1,1,2-tetrachloroethane can be absorbed by inhalation. This finding is supported by an animal study that showed substantial respiratory uptake of this substance (IARC 2014). Pharmacokinetic modelling suggests that 1,1,1,2-tetrachloroethane is likely widely distributed to tissues after systemic absorption (IARC, 2014). In experimental animal studies it was observed that the major urinary metabolite of 1,1,1,2-tetrachloroethane was trichloroethanol; other metabolites may include trichloroacetic acid, 1,1- dichloroethylene, and 1,1,2-trichloroethane. It can also be dechlorinated in the presence of oxygen (IARC, 2014). Studies in animals show that 1,1,1,2-tetrachloroethane is eliminated rapidly from the body, with most of it excreted 24 hours after absorption, and that elimination of 1,1,1,2-tetrachloroethane occurs mainly as urinary metabolites along with a small amount of exhaled carbon dioxide; at high doses it can be eliminated unchanged in exhaled air (IARC, 2014).

Available information suggests that exposure to 1,1,1,2-tetrachloroethane may produce adverse health effects, but the effects are not well studied in humans or animals. Acute inhalation exposure in humans may cause irritation of the respiratory tract, leading to coughing, wheezing, and shortness of breath, while direct contact may irritate the eyes and skin (Pohanish, 2012). Acute exposure in humans may also lead to central nervous system depression, weakness, tremor, reduced muscle coordination, drowsiness, respiratory difficulties, headache, vomiting and coma (National Research Council, 1977; Pohanish, 2012). One study using various animal species reported that acute exposure to 1,1,1,2-tetrachloroethane was associated with hepatotoxicity (microvacuolation and/or central lobular necrosis in the liver), and that the substance passed through the placental barrier and affected the fetus (National Research Council, 1977). Chronic exposure to 1,1,1,2-tetrachloroethane in animals has been reported to result in damage to the central nervous system, skin, kidneys, and liver (IARC, 2014; Pohanish, 2012; National Research Council, 1977). 1,1,1,2-Tetrachloroethane is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B) based on sufficient evidence for carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 2014).

The Government of Canada conducted a rapid screening assessment under the Chemicals Management Plan to determine whether 1,1,1,2-tetrachloroethane presents or may present a risk to the environment or human health as per the criteria set out in section 64 of the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Canada, 1999; Environment and Climate Change Canada and Health Canada, 2018). Based on the information available at the time of the assessment, it was concluded that 1,1,1,2-tetrachloroethane does not meet any of the criteria for being considered toxic under CEPA 1999 on the basis of negligible exposure of the general population of Canada and low ecological concern (Environment and Climate Change Canada and Health Canada, 2018).

1,1,1,2-Tetrachloroethane was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of 1,1,1,2-tetrachloroethane in blood can be an indicator of recent exposure to 1,1,1,2-tetrachloroethane and does not necessarily mean that an adverse effect will occur.

1,1,1,2-Tetrachloroethane was also analyzed in indoor air from households of CHMS participants in cycle 3 (2012–2013) and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.10.1: 1,1,1,2-Tetrachloroethane — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.10.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2576 Table footnote F <LOD <LOD <LOD <LOD
Males, 12–79 years
5 (2016–2017) 1281 Table footnote F <LOD <LOD <LOD <LOD
Females, 12–79 years
5 (2016–2017) 1295 Table footnote F <LOD <LOD <LOD <LOD
12–19 years
5 (2016–2017) 835 0 <LOD <LOD <LOD <LOD
20–39 years
5 (2016–2017) 591 0 <LOD <LOD <LOD <LOD
40–59 years
5 (2016–2017) 569 Table footnote F <LOD <LOD <LOD <LOD
60–79 years
5 (2016–2017) 581 Table footnote F <LOD <LOD <LOD <LOD

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 0.007 μg/L.

References

15.11 Tetrachloroethylene

Tetrachloroethylene (CASRN 127-18-4), commonly known as perchloroethylene, is a colourless liquid classified as a volatile organic compound (VOC) (Canada, 2003; Canada, 2011; Environment Canada and Health Canada, 1993; IARC, 2014). It is an industrial chemical produced commercially by chlorination of other hydrocarbons, including acetylene, via trichloroethylene (IARC, 2014). The use of tetrachloroethylene has changed over the years. In the mid-20th century, it was primarily used in the dry-cleaning industry and was the primary organic solvent used for vapour degreasing in metal-cleaning operations (IARC, 2014). In the 1980s, changes in use coincided with the introduction of environmental regulations and improved technology controls in Canada and internationally (Canada, 2011; Canada, 2003; IARC, 2014). Since the 1990s, the most common use of tetrachloroethylene was as a feedstock for producing fluorocarbons (IARC, 2014). However, under the Montreal Protocol on Substances that Deplete the Ozone Layer, the production of chlorofluorocarbons will be phased out by 2030 (IARC, 2014; UNEP, 2019). In Canada, tetrachloroethylene production ceased in 1992. Since then, importation has continued primarily for domestic use as a chemical feedstock and as a solvent in the dry-cleaning and metal-cleaning industries (Environment Canada and Health Canada, 1993; Health Canada, 2015).

Releases of tetrachloroethylene are mainly to the atmosphere by evaporative losses from anthropogenic sources (ATSDR, 2014; Environment Canada and Health Canada, 1993). Use and disposal of tetrachloroethylene and tetrachloroethylene-containing products can also result in releases to the environment via wastewater. A small amount of tetrachloroethylene is produced naturally in the environment by marine algae (Abrahamsson et al., 1995).

The primary route of exposure to tetrachloroethylene for the general population is through inhalation of indoor air containing tetrachloroethylene emitted by freshly dry-cleaned clothes, various building materials, automotive products, and other consumer products containing tetrachloroethylene (Won et al., 2013; Won et al., 2015; Environment Canada and Health Canada, 1993). Concentrations of tetrachloroethylene are higher in indoor air than in outdoor air in Canadian homes (Health Canada, 2010a; Health Canada 2010b; Health Canada, 2012; Health Canada, 2013). Tetrachloroethylene has been detected in drinking water; the ingestion of drinking water is, generally, a minor contributor to overall tetrachloroethylene exposure (Environment Canada and Health Canada, 1993; Health Canada, 2015). Exposure can also occur via ambient air and food (ATSDR, 2014; Environment Canada and Health Canada, 1993). Living near a dry-cleaning facility may also increase the potential for exposure (ATSDR, 2014; CDC, 2009; IARC, 2014).

Tetrachloroethylene is rapidly absorbed into the blood and distributed throughout the body, with some concentration in adipose tissue (ATSDR, 2014; Environment Canada and Health Canada, 1993; IARC, 2014). Tetrachloroethylene is metabolized in the kidney, liver, and lungs, forming the major metabolite trichloroacetic acid (TCA) and other minor metabolites, including trichloroethanol (IARC, 2014). Absorbed tetrachloroethylene is rapidly eliminated unchanged from the body via exhalation, followed by a slower excretion of metabolites in urine (IARC, 2014). The half-lives of tetrachloroethylene in vessel-rich tissue, muscle tissue, and adipose tissue are estimated to be 12 to 16 hours, 30 to 40 hours, and 55 hours, respectively (ATSDR, 2014). Tetrachloroethylene metabolites can be measured in urine, whereas tetrachloroethylene can be measured in exhaled air and blood; the latter is considered the most reliable biomarker of recent exposure (ATSDR, 2014; IARC, 2014).

Exposure to tetrachloroethylene is known to cause a number of health effects in humans. Acute exposure via inhalation, ingestion, and skin contact can result in irritation of membranes (ATSDR, 2014). The central nervous system is a primary target for tetrachloroethylene toxicity. At very high concentrations, acute exposure to tetrachloroethylene can induce central nervous system depression and loss of consciousness, while prolonged exposure may result in neurobehavioral effects and vision changes (ATSDR, 2014; Environment Canada and Health Canada, 1993). Tetrachloroethylene exposure is associated with narcotic and anesthetic effects that increase in severity with increasing exposure (ATSDR, 2014; Environment Canada and Health Canada, 1993; EPA, 2012). These neurological symptoms may be reversible following cessation of acute exposure; however, chronic exposures may result in more persistent neurological impairments (ATSDR, 2014; Environment Canada and Health Canada, 1993; IARC, 2014). Available animal data also identify the kidney, liver, reproductive system, and developing fetus as potential targets of tetrachloroethylene toxicity. Multiple cancer sites of interest have been evaluated by the International Agency for Research on Cancer (IARC) Expert Working Group; positive associations for cancer of the bladder in humans are consistently found (IARC, 2014). Tetrachloroethylene has been classified by IARC as probably carcinogenic to humans (Group 2A) on the basis of limited evidence in humans and sufficient evidence in laboratory animals, and as possibly carcinogenic to humans (Group III) by Environment Canada and Health Canada (Environment Canada and Health Canada, 1993; IARC, 2014).

The Government of Canada conducted a scientific assessment of the impact of tetrachloroethylene exposure on humans and the environment and concluded that it is toxic to the environment, but not to human health, as per criteria set out under the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Environment Canada and Health Canada, 1993). Tetrachloroethylene is listed on Schedule 1, List of Toxic Substances, under CEPA 1999 and is a risk-managed substance involving a full life cycle management approach to prevent or minimize its release into the environment (Canada, 1999). In Canada, Regulations for Tetrachloroethylene Use in Dry Cleaning and Reporting Requirements have been introduced to reduce releases of tetrachloroethylene from dry-cleaning facilities (Canada, 2011; Canada, 2003). The Government of Canada has also introduced Solvent Degreasing Regulations to reduce total Canadian consumption of trichloroethylene and tetrachloroethylene used in solvent-degreasing operations (Canada, 2003; Environment Canada, 2013a). Tetrachloroethylene is identified as being prohibited on the List of Prohibited and Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient Hotlist or simply the Hotlist), an administrative tool that Health Canada uses to communicate to manufacturers and others that certain substances, when present in a cosmetic, may not be compliant with requirements of the Food and Drugs Act or the Cosmetic Regulations (Health Canada, 2018).

In 2017, Health Canada published an Indoor Air Reference Level (IARL) for tetrachloroethylene (Health Canada, 2017). Tetrachloroethylene is part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013b).

Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, has developed a guideline for Canadian drinking water quality that establishes the maximum acceptable concentration for tetrachloroethylene in drinking water that is protective of human health (Health Canada, 2015). This guideline was developed based on neurological effects observed in humans and experimental animals and is considered protective of both cancer and non-cancer effects.

Tetrachloroethylene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of tetrachloroethylene in blood can be an indicator of exposure to tetrachloroethylene and does not necessarily mean that an adverse health effect will occur.

Tetrachloroethylene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013), cycle 3 (2012–2013), and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.11.1: Tetrachloroethylene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.11.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2453 44.1
(34.5–54.3)
<LOD <LOD 0.10
(0.067–0.14)
0.17Table 15.11.1 footnote E
(0.10–0.23)
4 (2014–2015) 2527 28.4
(22.6–34.9)
<LOD <LOD 0.066Table 15.11.1 footnote E
(0.022–0.11)
Table footnote F
5 (2016–2017) 2487 73.3
(55.5–85.8)
0.035Table 15.11.1 footnote E
(0.018–0.069)
<LOD 0.034Table 15.11.1 footnote E
(<LOD–0.057)
Table footnote F Table footnote F
Males, 12–79 years
3 (2012–2013) 1228 47.6
(37.8–57.6)
<LOD <LOD 0.13
(0.086–0.17)
0.19
(0.13–0.25)
4 (2014–2015) 1251 30.1
(23.7–37.3)
<LOD <LOD Table footnote F Table footnote F
5 (2016–2017) 1238 72.7
(50.7–87.4)
Table footnote F <LOD 0.038Table 15.11.1 footnote E
(<LOD–0.065)
Table footnote F Table footnote F
Females, 12–79 years
3 (2012–2013) 1225 40.7
(29.2–53.4)
<LOD <LOD 0.096Table 15.11.1 footnote E
(0.060–0.13)
0.13Table 15.11.1 footnote E
(0.039–0.22)
4 (2014–2015) 1276 26.7
(20.3–34.3)
<LOD <LOD 0.068Table 15.11.1 footnote E
(<LOD–0.12)
Table footnote F
5 (2016–2017) 1249 73.9
(59.1–84.8)
0.034Table 15.11.1 footnote E
(0.018–0.064)
<LOD 0.031Table 15.11.1 footnote E
(<LOD–0.050)
Table footnote F Table footnote F
12–19 years
3 (2012–2013) 739 37.9
(29.2–47.5)
<LOD <LOD Table footnote F Table footnote F
4 (2014–2015) 713 20.0
(14.3–27.4)
<LOD <LOD 0.042Table 15.11.1 footnote E
(<LOD–0.065)
Table footnote F
5 (2016–2017) 816 65.8
(45.6–81.5)
Table footnote F <LOD Table footnote F Table footnote F Table footnote F
20–39 years
3 (2012–2013) 543 47.7
(32.2–63.5)
<LOD <LOD 0.093Table 15.11.1 footnote E
(0.052–0.13)
0.15Table 15.11.1 footnote E
(0.080–0.23)
4 (2014–2015) 600 24.6Table 15.11.1 footnote E
(14.5–38.4)
<LOD <LOD Table footnote F Table footnote F
5 (2016–2017) 570 71.7
(51.4–85.9)
0.031Table 15.11.1 footnote E
(0.015–0.063)
<LOD 0.033Table 15.11.1 footnote E
(<LOD–0.056)
Table footnote F Table footnote F
40–59 years
3 (2012–2013) 587 40.3
(29.8–51.8)
<LOD <LOD 0.10Table 15.11.1 footnote E
(0.058–0.14)
0.13
(0.089–0.17)
4 (2014–2015) 625 28.4
(21.8–36.2)
<LOD <LOD 0.061Table 15.11.1 footnote E
(<LOD–0.10)
Table footnote F
5 (2016–2017) 546 75.9
(58.1–87.7)
Table footnote F <LOD Table footnote F Table footnote F Table footnote F
60–79 years
3 (2012–2013) 584 48.3
(36.6–60.2)
<LOD <LOD 0.16Table 15.11.1 footnote E
(0.062–0.25)
Table footnote F
4 (2014–2015) 589 38.3
(32.5–44.5)
<LOD <LOD 0.088Table 15.11.1 footnote E
(0.028–0.15)
Table footnote F
5 (2016–2017) 555 75.3
(56.5–87.8)
0.039Table 15.11.1 footnote E
(0.020–0.075)
<LOD 0.034Table 15.11.1 footnote E
(0.014–0.054)
Table footnote F Table footnote F

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.020, 0.020, and 0.013 μg/L, respectively.

References

15.12 Tetrahydrofuran

Tetrahydrofuran (CASRN 109-99-9) is a colourless, volatile liquid with an odour similar to ether or acetone (EPA, 2012). It is a high-production volume chemical (EPA, 2018 OECD, 2018) and is typically produced industrially by the Reppe Process involving the reaction of acetylene and formaldehyde, followed by hydrogenation and acid catalysis (Müller, 2012). Based on 2011 survey information collected pursuant to Section 71 of the Canadian Environmental Protection Act, 1999 (CEPA 1999), tetrahydrofuran was not reported to be manufactured in Canada (Environment and Climate Change Canada and Health Canada, 2018). The quantity of tetrahydrofuran imported into Canada has remained relatively steady over the last 30 years (Statistics Canada, 2018).

The single largest use of tetrahydrofuran in Canada and internationally is in the production of polytetramethylene ether glycol (PTMEG), an important component of synthetic elastic construction materials, thermoplastics and moulded elastomers, elastic Spandex fibres, and polyurethane coatings (Environment and Climate Change Canada and Health Canada, 2018; Müller, 2012; OECD, 2000). Other uses of tetrahydrofuran in Canada are in the production of adhesives such as PVC cement, varnish and paint removers, and paints and coatings. Tetrahydrofuran may also be present in nail adhesives and can be formed as an impurity during the manufacture of some resins used in food-packaging materials. It is also a formulant in pest control products currently registered in Canada (Environment and Climate Change Canada and Health Canada, 2018; Health Canada, 2018). There are some reports of its use in furniture polish and cleaners, laundry starch preparations, and stain removers, but no evidence of these uses was identified in Canada (Environment and Climate Change Canada and Health Canada, 2018). Tetrahydrofuran can be used in the production of cellophane, protective coatings, magnetic strips, and printing inks, and as an intermediate in the production of other chemicals, including acrylic acid, adipic acid, butadiene, butyrolactone, succinic acid, and 1,4-butanediol diacetate. It can also be used in the fabrication of materials for food packaging, transport, and storage, and in motor fuels, vitamins, hormones, pharmaceuticals, synthetic perfumes, organometallic compounds, and insecticides (EPA, 2012).

Tetrahydrofuran is not known to occur naturally (EPA, 2012). It may be present in ambient and indoor air from anthropogenic sources. Measured concentrations in Canadian ambient air are generally very low, but available monitoring data indicate higher levels in indoor air (Environment and Climate Change Canada and Health Canada, 2018). Tetrahydrofuran may be elevated in indoor air where polyvinyl chloride (PVC) cements or other consumer products containing tetrahydrofuran have been used (Environment and Climate Change Canada and Health Canada, 2018). Tetrahydrofuran has been identified as a volatile component of some foods (including coffee, cooked meat, honey, and blackberries), potentially formed from thermal degradation or chemical rearrangement of naturally occurring precursors during cooking or processing. Tetrahydrofuran has been identified (but not quantified) in the breast milk of mothers living in the United States; however, similar data in Canada are lacking (Environment and Climate Change Canada and Health Canada, 2018; Pellizzari et al., 1982).

Canadians are exposed to tetrahydrofuran primarily through indoor air. Given the use patterns of tetrahydrofuran and its physical-chemical properties (i.e., very high vapour pressure and low octanol-water partition coefficient), exposure of the general population from food and drinking water is expected to be much lower compared with exposure from air. Use of consumer products such as PVC cements and adhesives by the general population may result in exposure through inhalation or dermal contact (Environment and Climate Change Canada and Health Canada, 2018).

Tetrahydrofuran is readily absorbed by inhalation, with uptake ratios in humans shown to range from approximately 60% to 80% (EPA, 2012). Tetrahydrofuran has been shown to widely distribute from blood to various organs following inhalation in animal studies (EPA, 2012). Based on chronic studies of animals, the thymus and spleen are the organs with the highest levels of tetrahydrofuran following exposure, but it may also distribute to the brain, heart, kidney, liver, and lung, among other tissues. Tetrahydrofuran does not accumulate in organs. It rapidly decreases to background levels following cessation of exposure. Following absorption, tetrahydrofuran is oxidized by CYP450 enzymes in the liver—followed by paraoxonase 1 enzymatic hydrolysis and additional oxidation by cytosolic dehydrogenases to succinic acid—before undergoing further metabolic transformations to ultimately yield CO2, the major terminal metabolite of tetrahydrofuran, which is eliminated in exhaled air (EPA, 2012).

Occupational studies have reported that acute and chronic inhalation exposure to tetrahydrofuran is associated with central nervous system depression (including symptoms of headaches, dizziness, tiredness, and a diminished sense of smell), respiratory tract irritation (cough, chest pain, rhinorrhea, dyspnea), haematological changes, decreased white blood cells, and effects on the liver (e.g., increased liver enzymes) and kidney (autoimmune glomerulonephritis) (EPA, 2012). Systemic effects have been observed in experimental animal studies following inhalation of tetrahydrofuran, including decreased body weight, effects on the liver (e.g., centrilobular cytomegaly, hepatocellular necrosis), haematological alteration, increased organ weights, respiratory tract irritation, and immunotoxicity (EPA, 2012). Fetal toxicity and developmental effects have also been observed in animals following chronic inhalation exposures, including intrauterine mortality and reduced body weight (Environment and Climate Change Canada and Health Canada, 2018; EPA, 2012; OECD, 2000). Tetrahydrofuran is classified by the International Agency for Research on Cancer (IARC) as possibly carcinogenic to humans (Group 2B) based on sufficient evidence of carcinogenicity in experimental animals and inadequate evidence in humans (IARC, 2019).

The Government of Canada has conducted a science-based screening assessment under the Chemicals Management Plan to determine whether tetrahydrofuran presents or may present a risk to the environment or human health as per the criteria set out in section 64 of CEPA 1999 (Canada, 1999; Environment and Climate Change Canada and Health Canada, 2018). The assessment proposes to conclude that tetrahydrofuran is toxic under CEPA 1999 as it is considered harmful to human health (Environment and Climate Change Canada and Health Canada, 2018).

Tetrahydrofuran is also part of a larger class of volatile organic compounds (VOCs) that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has taken and proposed a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013).

Tetrahydrofuran was analyzed in whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of tetrahydrofuran in blood can be an indicator of a recent exposure to tetrahydrofuran and does not necessarily mean that an adverse health effect will occur.

Tetrahydrofuran was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013), cycle 3 (2012–2013), and cycle 4 (2014–2015). Further details on indoor air sampling are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.12.1: Tetrahydrofuran — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.12.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
5 (2016–2017) 2548 10.8
(8.3–13.8)
<LOD <LOD <LODTable 15.12.1 footnote E
(<LOD–0.019)
0.018
(0.017–0.019)
Males, 12–79 years
5 (2016–2017) 1265 10.7Table 15.12.1 footnote E
(6.6–17.0)
<LOD <LOD <LODTable 15.12.1 footnote E
(<LOD–0.019)
0.019
(<LOD–0.024)
Females, 12–79 years
5 (2016–2017) 1283 10.8
(8.3–13.9)
<LOD <LOD <LOD 0.018
(0.017–0.019)
12–19 years
5 (2016–2017) 827 9.8Table 15.12.1 footnote E
(6.0–15.8)
<LOD <LOD <LOD 0.016
(<LOD–0.018)
20–39 years
5 (2016–2017) 582 14.4Table 15.12.1 footnote E
(9.1–22.1)
<LOD <LOD 0.017
(<LOD–0.020)
0.019Table 15.12.1 footnote E
(<LOD–0.026)
40–59 years
5 (2016–2017) 561 7.0Table 15.12.1 footnote E
(4.7–10.4)
<LOD <LOD <LOD 0.017
(0.015–0.019)
60–79 years
5 (2016–2017) 578 11.3
(9.6–13.2)
<LOD <LOD 0.015
(<LOD–0.020)
0.020
(0.016–0.024)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LOD for cycle 5 is 0.015 μg/L.

References

15.13 Toluene

Toluene (CASRN 108-88-3) is a colourless liquid classified as a volatile organic compound (VOC). It is produced commercially, primarily through the conversion of petroleum to gasoline and other fuels or when recovered as a by-product in coke ovens and styrene-manufacturing industries (ATSDR, 2017; Environment Canada and Health Canada, 1992).

Toluene is used widely as an industrial solvent and as an intermediate in the production of a variety of chemicals. Major uses have included the manufacture of benzene, benzene derivatives, trinitrotoluene and toluene diisocyanate, and in the blending of gasoline fuels as octane boosters (ATSDR, 2017; CDC, 2009). It has also been widely used as a solvent in paints and finishes, adhesives, polymers and resins, dyes, automotive products, and some personal care products (ATSDR, 2017; Environment Canada and Health Canada, 1992; Health Canada, 2018). The use of toluene in solvent-based products and processes has decreased, as alternative formulations with lower VOC content (as well as alcohol-based and water-based products and processes) are now available.

Toluene is released to the environment from natural and anthropogenic sources. It has been measured in emissions from volcanoes, forest fires, natural gas deposits, and crude oil (Environment Canada and Health Canada, 1992). Primary anthropogenic sources of atmospheric toluene include the volatilization of petroleum fuels, toluene-based solvents, and thinners, motor vehicle exhaust, and the off-gassing of toluene from some building materials and consumer and automotive products (ATSDR, 2017; Environment Canada and Health Canada, 1992). Toluene can also be released to the environment in waste from manufacturing and processing facilities, from spills and accidental releases, and from the disposal of toluene-containing products (ATSDR, 2017; CCME, 2004; Environment Canada and Health Canada, 1992).

The most common route of exposure to toluene for the general population is inhalation; exposure is attributed predominantly to indoor air because indoor levels generally exceed outdoor levels and because people typically spend more time indoors than out (Health Canada, 2010a; Health Canada, 2010b; Health Canada, 2011; Health Canada 2012a; Health Canada, 2012b; Health Canada, 2013). Sources of toluene in indoor air include stored combustion equipment, various building materials, automotive products, furniture, candles, and mothballs (Won et al., 2013; Won et al., 2014; Won et al., 2015; Won and Yang, 2012). Toluene is also found in tobacco smoke; regular smoking in the home is a predictor of toluene in indoor air (Health Canada, 2012b; Wheeler et al., 2013). Smokers have considerably higher exposure to toluene than non-smokers (ATSDR, 2017). Inside residences, toluene levels in air have been shown to be higher in newer homes and homes with a garage on the property, and in homes where paint or paint remover has been used in the previous week (Wheeler et al., 2013). Although toluene has been detected in drinking water and in certain foods, these are not considered to constitute major sources of exposure for the general population (Environment Canada and Health Canada, 1992; Health Canada, 2014).

Following inhalation, toluene is readily absorbed and distributed throughout the body (ATSDR, 2017; Environment Canada and Health Canada, 1992). The majority of absorbed toluene is rapidly eliminated from the body, with a small amount in adipose tissues eliminated more slowly (ATSDR, 2017). Up to 20% of absorbed toluene is exhaled unchanged; less than 1% is excreted unchanged in the urine (ATSDR, 2017; Donald et al., 1991). The elimination of toluene following inhalation has estimated half-lives ranging from less than three minutes to 12 hours in blood and from 0.5 to 3 days in human subcutaneous adipose tissues (ATSDR, 2017). The level of toluene in blood is the most accurate biomarker of exposure and is reflective of recent exposure (ATSDR, 2017; CDC, 2009).

Toluene exposure can be irritating to the eyes, nose, throat, lungs, and skin, and has been associated with symptoms of headaches, dizziness, reduced coordination, and feelings of intoxication (ATSDR, 2000; CCOHS, 2018; Health Canada, 2011; Health Canada, 2012b; IARC, 1999). Acute inhalation exposure has generally been associated with reversible neurological symptoms; chronic exposure is associated with impaired neurological function, including cognitive and neuromuscular performance as well as negative effects on colour vision and hearing (ATSDR, 2017; CCOHS, 2018; CDC, 2009; Health Canada, 2011; IARC, 1999). Studies in laboratory animals exposed to toluene provide supporting evidence for behavioural changes, hearing loss and subtle changes in brain structure, brain electrophysiology, and brain chemistry (ATSDR, 2017; Bowen and Hannigan, 2006; Gospe and Zhou, 2000). Exposure to high levels of toluene in humans during pregnancy has been associated with fetal toxicity and developmental effects in children at levels associated with potential maternal toxicity, such as in solvent abuse (ATSDR, 2017; Bowen and Hannigan, 2006; Donald et al., 1991; Yücel et al., 2008). The International Agency for Research on Cancer (IARC) has classified toluene as Group 3, not classifiable as to its carcinogenicity to humans (IARC, 1999).

Under the Canadian Environmental Protection Act, 1999 Health Canada and Environment Canada concluded that toluene is not a concern for human life or health based on measured environmental concentrations (Environment Canada and Health Canada, 1992). Toluene is part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013), as well as from on-road (Canada, 2003; Canada, 2015) and off-road (Canada, 2013; Canada, 2017) engines and vehicles.

In 2011, Health Canada released a residential indoor air quality guideline for both short- and long-term exposure to toluene (Health Canada, 2011). Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, developed a guideline for Canadian drinking water quality that establishes a maximum acceptable concentration for toluene that is protective of human health, as well as an aesthetic objective for toluene based on its odour threshold (Health Canada, 2014). The guideline was developed based on several neurological end points reported in human occupational studies.

Toluene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of toluene in blood can be an indicator of recent exposure to toluene and does not necessarily mean that an adverse health effect will occur.

Toluene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Statistics Canada, 2013; Wheeler et al., 2013; Zhu et al. 2013), cycle 3 (2012–2013) (Statistics Canada, 2015), and cycle 4 (2014–2015), and in tap water from households in cycles 3 and 4. Further details on the indoor air and tap water studies are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air and tap water data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.13.1: Toluene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.13.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2449 99.5
(98.9–99.8)
0.096
(0.083–0.11)
0.036
(0.030–0.042)
0.079
(0.067–0.090)
0.39
(0.32–0.46)
0.58
(0.46–0.71)
4 (2014–2015) 2384 100
(99.6–100)
0.12
(0.094–0.16)
0.044
(0.028–0.059)
0.11
(0.076–0.14)
0.42
(0.27–0.58)
0.55
(0.39–0.71)
5 (2016–2017) 2558 99.2
(94.9–99.9)
0.085
(0.070–0.10)
0.029
(0.023–0.036)
0.071
(0.057–0.084)
0.37
(0.29–0.44)
0.55
(0.46–0.64)
Males, 12–79 years
3 (2012–2013) 1224 99.4
(98.5–99.7)
0.098
(0.081–0.12)
0.034
(0.025–0.043)
0.081
(0.066–0.095)
0.42
(0.33–0.51)
0.59
(0.42–0.77)
4 (2014–2015) 1182 99.9
(99.1–100)
0.13
(0.10–0.18)
0.044Table 15.13.1 footnote E
(0.023–0.065)
0.12
(0.085–0.15)
0.46
(0.30–0.61)
0.65
(0.41–0.88)
5 (2016–2017) 1270 99.8
(98.9–100)
0.097
(0.082–0.12)
0.029
(0.024–0.035)
0.078
(0.065–0.090)
0.42
(0.29–0.55)
0.64Table 15.13.1 footnote E
(0.40–0.87)
Females, 12–79 years
3 (2012–2013) 1225 99.6
(99.0–99.9)
0.093
(0.081–0.11)
0.037
(0.034–0.041)
0.077
(0.064–0.089)
0.35
(0.24–0.46)
0.55Table 15.13.1 footnote E
(0.34–0.76)
4 (2014–2015) 1202 100 0.11
(0.086–0.15)
0.043
(0.030–0.055)
0.10Table 15.13.1 footnote E
(0.058–0.14)
0.37Table 15.13.1 footnote E
(0.17–0.57)
0.53
(0.43–0.64)
5 (2016–2017) 1288 98.6
(90.8–99.8)
0.074
(0.058–0.094)
0.028
(0.020–0.036)
0.061
(0.047–0.076)
0.28Table 15.13.1 footnote E
(0.16–0.40)
0.48
(0.37–0.60)
12–19 years
3 (2012–2013) 732 99.6
(97.2–99.9)
0.074
(0.066–0.083)
0.034
(0.026–0.042)
0.070
(0.058–0.082)
0.19
(0.14–0.24)
0.26
(0.19–0.32)
4 (2014–2015) 681 100 0.096
(0.070–0.13)
0.039
(0.028–0.050)
0.097
(0.061–0.13)
0.22Table 15.13.1 footnote E
(0.14–0.31)
0.30Table 15.13.1 footnote E
(0.17–0.44)
5 (2016–2017) 832 99.5
(95.1–99.9)
0.065
(0.053–0.080)
0.028
(0.023–0.032)
0.059
(0.046–0.072)
0.17
(0.11–0.22)
0.25
(0.17–0.34)
20–39 years
3 (2012–2013) 533 99.2
(97.0–99.8)
0.089
(0.069–0.11)
0.036
(0.028–0.045)
0.074
(0.050–0.098)
0.29Table 15.13.1 footnote E
(0.16–0.43)
0.42Table 15.13.1 footnote E
(0.23–0.61)
4 (2014–2015) 574 100 0.12
(0.094–0.16)
0.047Table 15.13.1 footnote E
(0.027–0.067)
0.12Table 15.13.1 footnote E
(0.076–0.17)
0.30Table 15.13.1 footnote E
(0.19–0.41)
0.46
(0.30–0.61)
5 (2016–2017) 587 98.5
(89.3–99.8)
0.086
(0.066–0.11)
0.026
(0.018–0.034)
0.075Table 15.13.1 footnote E
(0.044–0.11)
0.35
(0.25–0.44)
0.51
(0.42–0.60)
40–59 years
3 (2012–2013) 594 99.9
(99.6–100)
0.12
(0.10–0.14)
0.041
(0.033–0.049)
0.085
(0.071–0.10)
0.58
(0.38–0.79)
0.86
(0.64–1.1)
4 (2014–2015) 580 100
(99.6–100)
0.13
(0.10–0.18)
0.045
(0.029–0.060)
0.11
(0.071–0.14)
0.51
(0.34–0.67)
0.72
(0.55–0.88)
5 (2016–2017) 562 99.6
(96.5–100)
0.091
(0.073–0.11)
0.029
(0.019–0.040)
0.072
(0.060–0.085)
0.45
(0.29–0.60)
0.65Table 15.13.1 footnote E
(0.36–0.93)
60–79 years
3 (2012–2013) 590 99.1
(89.3–99.9)
0.086
(0.070–0.11)
0.031
(0.024–0.039)
0.080
(0.065–0.096)
0.31
(0.22–0.40)
0.46
(0.39–0.53)
4 (2014–2015) 549 99.8
(98.6–100)
0.12
(0.089–0.16)
0.038Table 15.13.1 footnote E
(0.023–0.054)
0.099Table 15.13.1 footnote E
(0.061–0.14)
0.49
(0.34–0.64)
0.70
(0.46–0.94)
5 (2016–2017) 577 99.3
(96.3–99.9)
0.086
(0.071–0.10)
0.031
(0.025–0.036)
0.069
(0.059–0.079)
0.39
(0.28–0.49)
0.54
(0.43–0.64)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.011, 0.011, and 0.012 μg/L, respectively.

References

15.14 Trichloroethylene

Trichloroethylene (CASRN 79-01-6) is a colourless liquid classified as a volatile organic compound (VOC). It has been produced commercially by chlorinating acetylene and ethylene since the 1920s (ATSDR, 1997; IARC, 1995). There has been a general decline in demand for trichloroethylene over the years (Health Canada, 2005; IARC, 2014). This decline may be due to several factors, including use of alternative solvents, an increase in solvent recovery/recycling by users, and the introduction of regulations and controls to address concerns about environmental, health, and safety implications of chlorinated solvents (Health Canada, 2005; IARC, 2014). In Canada, production of trichloroethylene stopped in 1985 (Health Canada, 2005). Since then, it has continued to be imported for use primarily as a solvent for the vapour-degreasing and cold-cleaning of metal parts. Smaller amounts are used in dry-cleaning operations, specialty paints and paint removers, and various other household products (Environment Canada, 2013a; Environment Canada, 2013b; Health Canada, 2005). Trichloroethylene is also used as a chemical intermediate in the production of other chemicals (IARC, 2014).

Trichloroethylene enters the environment primarily through evaporation from anthropogenic sources (ATSDR, 1997; Environment Canada, 2013b). The majority of anthropogenic releases enter the atmosphere, but it can also enter the environment via wastewater during the production, use, and disposal of trichloroethylene and trichloroethylene-containing products. A small amount of trichloroethylene is produced naturally in the environment by marine algae (Abrahamsson et al., 1995).

The most common exposure route for the general population is inhalation of indoor air containing trichloroethylene emitted from specialty paints, adhesives, and household products (CDC, 2009; Environment Canada and Health Canada, 1993). Canadians may also be exposed to trichloroethylene through its presence in drinking water, ambient air, and food (Health Canada, 2005).

Following all routes of exposure, trichloroethylene is rapidly and nearly completely absorbed into the blood and distributed throughout the body (ATSDR, 1997; Environment Canada and Health Canada, 1993; EPA, 2011). Absorbed trichloroethylene is distributed mainly to the brain, kidney, liver, muscle, and adipose tissue (ATSDR, 1997). Trichloroethylene is metabolized in the kidney, liver, and lungs, forming the major metabolites trichloroacetic acid (TCA) and trichloroethanol (TCOH) (ATSDR, 1997; EPA, 2011). Absorbed trichloroethylene is rapidly eliminated from the body via exhalation of trichloroethylene and urinary excretion of the metabolites along with minimal amounts of unchanged trichloroethylene (ATSDR, 1997; EPA, 2011). The most reliable biomarker of recent exposure to trichloroethylene is its direct measurement in blood and breath (ATSDR, 1997; IARC, 1995). Measurement of the metabolites TCA and TCOH in blood and urine is less reliable because of intra-individual differences in urinary concentrations and a lack of specificity for trichloroethylene exposure (ATSDR, 1997; IARC, 1995).

Exposure to trichloroethylene is known to cause a number of health effects in humans. Acute exposure via inhalation, ingestion, and skin contact can result in irritation (ATSDR, 1997; Health Canada, 2005; IARC, 1995). Trichloroethylene exposure is also associated with narcotic and anesthetic effects that increase in severity with increasing exposure (Environment Canada and Health Canada, 1993; IARC, 1995). These neurological symptoms may be reversible following cessation of acute exposure; however, chronic exposures may result in more persistent neurological impairments (ATSDR, 1997; Environment Canada and Health Canada, 1993; EPA, 2011). The International Agency for Research on Cancer (IARC) has classified trichloroethylene as carcinogenic to humans (Group 1) based on sufficient evidence for cancer of the kidney in humans and strong support from experimental animal studies (IARC, 2014). A positive association has also been shown between trichloroethylene exposure and cancers of the liver and biliary tract and non-Hodgkin lymphoma (EPA, 2011; IARC, 2014; WHO, 2000).

The Government of Canada conducted a scientific assessment of the impact of trichloroethylene exposure on humans and the environment, and concluded that trichloroethylene may enter the environment in quantities or under conditions that may constitute a danger to human life or health as per criteria set out under the Canadian Environmental Protection Act, 1999 (CEPA, 1999) (Environment Canada and Health Canada, 1993). Trichloroethylene is listed on Schedule 1, List of Toxic Substances, under CEPA 1999 (Canada, 1999). Under CEPA 1999, the Government of Canada published Solvent Degreasing Regulations to reduce total Canadian consumption of trichloroethylene and tetrachloroethylene used in solvent-degreasing operations (Environment Canada, 2013c). Trichloroethylene is part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013d).

A guideline establishing the maximum acceptable concentration for trichloroethylene in Canadian drinking water was developed by Health Canada in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water (Health Canada, 2005). The guideline was developed based upon developmental toxicity and is considered protective for both cancer and non-cancer effects.

Trichloroethylene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017). Data are presented as µg/L blood. Finding a measurable amount of trichloroethylene in blood can be an indicator of exposure to trichloroethylene and does not necessarily mean that an adverse health effect will occur.

Trichloroethylene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013).

Table 15.14.1: Trichloroethylene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.14.1 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2474 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 2527 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 2576 Table footnote F <LOD <LOD <LOD <LOD
Males, 12–79 years
3 (2012–2013) 1240 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 1251 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 1281 Table footnote F <LOD <LOD <LOD <LOD
Females, 12–79 years
3 (2012–2013) 1234 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 1276 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 1295 Table footnote F <LOD <LOD <LOD <LOD
12–19 years
3 (2012–2013) 746 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 713 0 <LOD <LOD <LOD <LOD
5 (2016–2017) 835 Table footnote F <LOD <LOD <LOD <LOD
20–39 years
3 (2012–2013) 543 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 600 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 591 Table footnote F <LOD <LOD <LOD <LOD
40–59 years
3 (2012–2013) 594 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 625 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 569 Table footnote F <LOD <LOD <LOD <LOD
60–79 years
3 (2012–2013) 591 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 589 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 581 Table footnote F <LOD <LOD <LOD <LOD

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.027, 0.027, and 0.010 μg/L, respectively.

References

15.15 Trihalomethanes

Disinfection by-products are a group of chemical compounds formed when water disinfection agents (e.g., chlorine, chloramines, ozone, chlorine dioxide) interact with organic precursors or bromide naturally present in water (CCME, 1999; CDC, 2009; Health Canada, 2006). Disinfection by-products include, among others, trihalomethanes (THMs), haloacetic acids, haloacetonitriles, haloketones, and chlorophenols. THM formation increases as a function of the concentration of chlorine and organic matter; in the presence of bromide, brominated THMs are formed (Health Canada, 2006). In cycles 3, 4, and 5 of the Canadian Health Measures Survey (CHMS), four THMs were measured: bromodichloromethane, dibromochloromethane, bromoform, and chloroform. Each of these compounds consists of three halogen groups attached to a single carbon atom; all are classified as volatile organic compounds (VOCs) (CCME, 1999). Chloroform is the most common THM and the most frequently measured disinfection by-product in chlorinated drinking water in Canada (ATSDR, 2005; Health Canada, 2006).

Table 15.15.1: Trihalomethanes measured in the Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Trihalomethane CASRN
Bromodichloromethane 75-27-4
Dibromochloromethane 124-48-1
Tribromomethane (Bromoform) 75-25-2
Trichloromethane (Chloroform) 67-66-3

The four THMs are also commercially produced chemicals (ATSDR, 1999; ATSDR, 2005). Chloroform and bromodichloromethane are used as chemical intermediates in the manufacturing of organic chemicals and as solvents, although chloroform has not been manufactured in Canada since 1978 (ATSDR, 2005; Health Canada, 2006). In Canada, the use of chloroform as an anesthetic has been discontinued, and its use in dentifrices, liniments, and antitussives has been banned (CCME, 1999; Environment Canada and Health Canada, 2001). Dibromochloromethane is used as an intermediate in the manufacture of refrigerants, pesticides, propellants, and other organic chemicals (Health Canada, 2006). Bromoform is used as a solvent in the synthesis of pharmaceuticals and in fire-resistant chemicals, as well as in gauge fluid used in the aircraft and shipbuilding industries (Health Canada, 2006).

A small proportion of THMs present in the environment may be due to natural production by marine algae and by natural degradation and transformation processes (ATSDR, 1999; ATSDR, 2005). Anthropogenic sources are generally considered to be larger contributors of THMs in the environment than natural sources. In Canada, the major anthropogenic sources of THMs are disinfected water from drinking water treatment plants, chlorinated effluents from municipal wastewater treatment plants and industrial plants, and cooling waters from power plants and industrial plants (Environment Canada and Health Canada, 1993). Chlorine use in the treatment of drinking water has virtually eliminated waterborne diseases because of its ability to kill or inactivate most microorganisms commonly found in water (Health Canada, 2006). It is used in the majority of drinking water treatment plants in Canada to treat the water directly in the treatment plant and/or to maintain a chlorine residual in the distribution system to prevent bacterial regrowth (Health Canada, 2006). Effluent wastewaters are disinfected to protect downstream municipal water supplies, recreational waters, and shellfish-growing areas from bacterial contamination and other microorganisms that cause waterborne disease (Environment Canada and Health Canada, 1993). In addition to drinking water, disinfection effluents and cooling waters, anthropogenic sources of THMs include chemical manufacturing plants, industrial sites, swimming pools, hot tubs, and water parks (ATSDR, 2005; CCME, 1999; Health Canada, 2006).

The general population is exposed to THMs primarily by drinking chlorinated water, through inhalation during showering and bathing, and by skin absorption during bathing and swimming (CDC, 2009; Environment Canada and Health Canada, 2001; Health Canada, 2006). Minor exposures may occur from the consumption of food and beverages (Health Canada, 2006). Swimming pools and hot tubs are additional sources of THM exposure (Aggazzotti et al., 1998).

Following ingestion, all four THMs are rapidly absorbed into the blood and distributed throughout the body, primarily in the fat, blood, liver, kidney, lungs, and nervous system (ATSDR, 1989; Health Canada, 2006; WHO, 2005). THMs are well absorbed following both oral and inhalation exposure, with dermal exposure as another potentially significant route of exposure (ATSDR, 1989; Health Canada, 2006; IPCS, 2000; WHO, 2005). Estimated half-lives for THMs in the body generally range from 1.5 hours to six hours; in a study of orally exposed laboratory animals, about 95% of absorbed bromodichloromethane was eliminated from the body in eight hours (ATSDR, 1989; Health Canada, 2006; WHO, 2005). Absorbed THMs are metabolized primarily to carbon dioxide and/or carbon monoxide, and are mainly eliminated from the body by exhalation of unchanged compounds and volatile metabolites, with only minor amounts excreted in the urine and less in the feces (Health Canada, 2006; IPCS, 2000). Unchanged disinfection by-products measured in blood are the most accurate biomarkers of exposure and reflect recent exposures (CDC, 2009).

Each of the four THMs is irritating to the eyes and respiratory tract. Acute inhalation exposure has been associated with reddening of the face (Health Canada, 2006; IPCS, 2000; WHO, 2005). Acute high-level inhalation and oral exposures to these disinfection by-products in laboratory animals induce general narcotic and anesthetic effects that increase in severity with exposure level, and are generally reversible following cessation of exposure (Health Canada, 2006; IPCS, 2000; WHO, 2005). Similar effects can be expected to occur in humans. Some animal studies indicate that exposure to high doses of bromoform or dibromochloromethane may also lead to liver and kidney injury within a short period of time (ATSDR, 2005). THMs containing bromine, such as bromodichloromethane, may be more toxic than chloroform and other chlorine-containing disinfection by-products according to experimental animal studies (Health Canada, 2006). Studies in humans and animals suggest a link between reproductive effects and exposure to high levels of trihalomethanes; however, the evidence is inconclusive (Health Canada, 2006). Chronic exposures to THMs in drinking water are weakly and inconsistently associated with cancers of the liver, kidney, colon, rectum, brain, pancreas, and bladder in human epidemiological studies (Health Canada, 2006; IPCS, 2000; WHO, 2005). Results of studies in laboratory animals chronically exposed by the oral route to high levels of individual THMs provide supporting evidence of an association among cancers of the kidney, liver, and intestines with exposures to disinfection by-products (ATSDR, 1989; Health Canada, 2006; WHO, 2005). Based upon available evidence in laboratory animals, chloroform and bromodichloromethane have been classified as possibly carcinogenic to humans (Group 2B) by the International Agency for Research on Cancer (IARC, 1999a; IARC, 1999b). There is insufficient evidence to determine whether or not bromoform, dibromochloromethane, and chlorinated drinking water are carcinogenic (IARC, 1991; IARC, 1999a).

Health Canada and Environment Canada have reviewed and assessed chlorinated wastewater effluents, defined as those effluents to which chlorine or chlorination agents are added for disinfection, under the Canadian Environmental Protection Act, 1999 (CEPA 1999). The screening assessment concluded that chlorinated wastewater effluents discharged to the Canadian environment by municipal wastewater treatment plants are a concern for the environment (Environment Canada and Health Canada, 1993). However, there was insufficient information to determine whether chlorinated wastewater effluents are harmful to human health. Chlorinated wastewater effluents are listed on Schedule 1, List of Toxic Substances, under CEPA 1999 (Canada, 1999). Under Canada's Food and Drugs Regulations, manufacturers are not permitted to import or sell a drug for human use in Canada that contains chloroform (Canada, 1978; Environment Canada and Health Canada, 2001).

Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, has developed a guideline for Canadian drinking water quality that establishes a maximum acceptable concentration for total THMs (defined as the sum of chloroform, bromoform, dibromochloromethane, and bromodichloromethane) in drinking water (Health Canada, 2006). The Canadian guideline states that utilities should make every effort to maintain concentrations as low as reasonably achievable without compromising the effectiveness of disinfection (Health Canada, 2006). The approach to reducing THM exposure is generally focused on reducing the formation of chlorinated disinfection by-products. This can be achieved by removing organic matter from the water before chlorine is added, by optimizing the disinfection process or using alternative disinfection strategies, or by using a different water source.

Bromodichloromethane, dibromochloromethane, bromoform, and chloroform were analyzed in the whole blood of CHMS cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017) participants aged 12–79 years. Data are presented as µg/L blood. Finding a measurable amount of THMs in blood can be an indicator of exposure to THMs and does not necessarily mean that an adverse health effect will occur.

Bromodichloromethane, dibromochloromethane, bromoform, and chloroform were also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Zhu et al., 2013a, 2013b), cycle 3 (2012–2013), and cycle 4 (2014–2015), and in tap water from households in cycles 3 and 4. Further details on the indoor air and tap water studies are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air and tap water data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.15.2: Bromodichloromethane — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.15.2 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2499 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 2527 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 2576 11.3Table 15.15.2 footnote E
(5.9–20.4)
<LOD <LOD <LODTable 15.15.2 footnote E
(<LOD–0.0078)
0.0076Table 15.15.2 footnote E
(<LOD–0.011)
Males, 12–79 years
3 (2012–2013) 1245 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 1251 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 1281 10.2Table 15.15.2 footnote E
(5.4–18.5)
<LOD <LOD Table footnote F 0.0074Table 15.15.2 footnote E
(<LOD–0.011)
Females, 12–79 years
3 (2012–2013) 1254 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 1276 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 1295 12.3Table 15.15.2 footnote E
(6.0–23.3)
<LOD <LOD 0.0055Table 15.15.2 footnote E
(<LOD–0.0080)
0.0079Table 15.15.2 footnote E
(<LOD–0.011)
12–19 years
3 (2012–2013) 744 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 713 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 835 12.7Table 15.15.2 footnote E
(7.1–21.6)
<LOD <LOD <LOD 0.0087
(0.0059–0.012)
20–39 years
3 (2012–2013) 556 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 600 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 591 12.3Table 15.15.2 footnote E
(6.5–21.9)
<LOD <LOD 0.0050Table 15.15.2 footnote E
(<LOD–0.0083)
Table footnote F
40–59 years
3 (2012–2013) 595 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 625 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 569 Table footnote F <LOD <LOD <LOD 0.0068Table 15.15.2 footnote E
(<LOD–0.010)
60–79 years
3 (2012–2013) 604 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 589 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 581 12.3Table 15.15.2 footnote E
(5.9–23.9)
<LOD <LOD 0.0051Table 15.15.2 footnote E
(<LOD–0.0079)
0.0076Table 15.15.2 footnote E
(<LOD–0.011)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.012, 0.012, and 0.005 μg/L, respectively.

Table 15.15.3: Dibromochloromethane — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.15.3 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2527 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 2499 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 2576 5.8Table 15.15.3 footnote E
(3.2–10.5)
<LOD <LOD <LOD <LODTable 15.15.3 footnote E
(<LOD–0.0061)
Males, 12–79 years
3 (2012–2013) 1263 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 1233 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 1281 7.8Table 15.15.3 footnote E
(4.1–14.4)
<LOD <LOD <LOD 0.0051Table 15.15.3 footnote E
(<LOD–0.0070)
Females, 12–79 years
3 (2012–2013) 1264 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 1266 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 1295 3.9Table 15.15.3 footnote E
(2.0–7.6)
<LOD <LOD <LOD <LOD
12–19 years
3 (2012–2013) 757 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 704 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 835 7.5Table 15.15.3 footnote E
(4.5–12.3)
<LOD <LOD <LOD 0.0059
(<LOD–0.0076)
20–39 years
3 (2012–2013) 557 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 596 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 591 Table footnote F <LOD <LOD <LOD 0.0052Table 15.15.3 footnote E
(<LOD–0.0083)
40–59 years
3 (2012–2013) 604 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 617 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 569 Table footnote F <LOD <LOD <LOD <LOD
60–79 years
3 (2012–2013) 609 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 582 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 581 Table footnote F <LOD <LOD <LOD <LODTable 15.15.3 footnote E
(<LOD–0.0058)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.0070, 0.0070, and 0.005 μg/L, respectively.

Table 15.15.4: Tribromomethane (Bromoform) — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.15.4 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2496 6.4Table 15.15.4 footnote E
(3.4–11.8)
<LOD <LOD <LOD 0.010Table 15.15.4 footnote E
(<LOD–0.015)
4 (2014–2015) 2527 2.6Table 15.15.4 footnote E
(1.6–4.3)
<LOD <LOD <LOD <LOD
5 (2016–2017) 2576 3.4Table 15.15.4 footnote E
(2.0–5.8)
<LOD <LOD <LOD <LOD
Males, 12–79 years
3 (2012–2013) 1244 6.5Table 15.15.4 footnote E
(3.4–11.8)
<LOD <LOD <LOD <LOD
4 (2014–2015) 1251 3.5Table 15.15.4 footnote E
(1.7–7.1)
<LOD <LOD <LOD <LOD
5 (2016–2017) 1281 3.7Table 15.15.4 footnote E
(2.1–6.3)
<LOD <LOD <LOD <LOD
Females, 12–79 years
3 (2012–2013) 1252 6.4Table 15.15.4 footnote E
(3.0–13.1)
<LOD <LOD <LOD <LODTable 15.15.4 footnote E
(<LOD–0.013)
4 (2014–2015) 1276 1.7Table 15.15.4 footnote E
(1.0–2.8)
<LOD <LOD <LOD <LOD
5 (2016–2017) 1295 Table footnote F <LOD <LOD <LOD <LOD
12–19 years
3 (2012–2013) 744 4.7Table 15.15.4 footnote E
(2.3–9.3)
<LOD <LOD <LOD <LOD
4 (2014–2015) 713 3.9Table 15.15.4 footnote E
(1.9–7.9)
<LOD <LOD <LOD <LOD
5 (2016–2017) 835 2.6Table 15.15.4 footnote E
(1.4–4.9)
<LOD <LOD <LOD <LOD
20–39 years
3 (2012–2013) 554 Table footnote F <LOD <LOD <LOD <LOD
4 (2014–2015) 600 Table footnote F <LOD <LOD <LOD <LOD
5 (2016–2017) 591 2.4Table 15.15.4 footnote E
(1.6–3.5)
<LOD <LOD <LOD <LOD
40–59 years
3 (2012–2013) 595 7.8Table 15.15.4 footnote E
(4.3–14.0)
<LOD <LOD <LOD <LOD
4 (2014–2015) 625 1.5Table 15.15.4 footnote E
(0.7–3.2)
<LOD <LOD <LOD <LOD
5 (2016–2017) 569 Table footnote F <LOD <LOD <LOD <LOD
60–79 years
3 (2012–2013) 603 Table footnote F <LOD <LOD <LOD Table footnote F
4 (2014–2015) 589 2.1Table 15.15.4 footnote E
(1.1–3.7)
<LOD <LOD <LOD <LOD
5 (2016–2017) 581 3.1Table 15.15.4 footnote E
(1.6–5.9)
<LOD <LOD <LOD <LOD

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.010, 0.010, and 0.013 μg/L, respectively.

Table 15.15.5: Trichloromethane (Chloroform) — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.15.5 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2527 19.6Table 15.15.5 footnote E
(13.2–28.2)
<LOD <LOD 0.021
(0.016–0.026)
0.029
(0.019–0.038)
4 (2014–2015) 2527 26.3Table 15.15.5 footnote E
(16.1–39.8)
<LOD <LOD 0.028Table 15.15.5 footnote E
(<LOD–0.043)
0.043Table 15.15.5 footnote E
(0.022–0.064)
5 (2016–2017) 2510 69.6
(55.9–80.5)
0.011
(0.0077–0.015)
<LOD 0.0098Table 15.15.5 footnote E
(<LOD–0.014)
0.042Table 15.15.5 footnote E
(0.023–0.061)
0.067Table 15.15.5 footnote E
(0.035–0.10)
Males, 12–79 years
3 (2012–2013) 1263 18.1
(12.5–25.5)
<LOD <LOD 0.021
(0.015–0.027)
0.035Table 15.15.5 footnote E
(0.018–0.052)
4 (2014–2015) 1251 25.0Table 15.15.5 footnote E
(15.0–38.6)
<LOD <LOD Table footnote F 0.046Table 15.15.5 footnote E
(0.022–0.069)
5 (2016–2017) 1245 70.5
(55.6–82.0)
0.011
(0.0079–0.014)
<LOD 0.0099Table 15.15.5 footnote E
(<LOD–0.014)
0.041Table 15.15.5 footnote E
(0.026–0.056)
0.061Table 15.15.5 footnote E
(0.036–0.086)
Females, 12–79 years
3 (2012–2013) 1264 21.2Table 15.15.5 footnote E
(13.3–32.0)
<LOD <LOD 0.021
(0.016–0.027)
0.028
(0.019–0.037)
4 (2014–2015) 1276 27.6Table 15.15.5 footnote E
(16.4–42.6)
<LOD <LOD 0.030Table 15.15.5 footnote E
(0.016–0.045)
0.039Table 15.15.5 footnote E
(0.016–0.062)
5 (2016–2017) 1265 68.7
(54.1–80.3)
0.011
(0.0073–0.015)
<LOD 0.0097Table 15.15.5 footnote E
(<LOD–0.015)
0.042Table 15.15.5 footnote E
(0.017–0.067)
0.075Table 15.15.5 footnote E
(0.036–0.11)
12–19 years
3 (2012–2013) 757 18.1Table 15.15.5 footnote E
(11.9–26.6)
<LOD <LOD 0.020Table 15.15.5 footnote E
(<LOD–0.028)
0.031Table 15.15.5 footnote E
(<LOD–0.049)
4 (2014–2015) 713 27.9Table 15.15.5 footnote E
(17.2–41.8)
<LOD <LOD 0.028Table 15.15.5 footnote E
(0.017–0.038)
0.040Table 15.15.5 footnote E
(0.015–0.066)
5 (2016–2017) 810 70.0
(54.4–82.0)
0.010
(0.0074–0.014)
<LOD 0.0096Table 15.15.5 footnote E
(<LOD–0.014)
0.039Table 15.15.5 footnote E
(0.020–0.058)
0.062
(0.046–0.079)
20–39 years
3 (2012–2013) 557 22.9Table 15.15.5 footnote E
(12.9–37.4)
<LOD <LOD 0.023
(0.016–0.029)
0.036Table 15.15.5 footnote E
(0.015–0.058)
4 (2014–2015) 600 30.2Table 15.15.5 footnote E
(17.7–46.5)
<LOD <LOD 0.030Table 15.15.5 footnote E
(0.016–0.045)
Table footnote F
5 (2016–2017) 577 68.7
(51.6–81.9)
0.011Table 15.15.5 footnote E
(0.0074–0.016)
<LOD 0.011Table 15.15.5 footnote E
(<LOD–0.017)
0.043Table 15.15.5 footnote E
(0.023–0.062)
0.087Table 15.15.5 footnote E
(0.026–0.15)
40–59 years
3 (2012–2013) 604 17.2Table 15.15.5 footnote E
(9.8–28.3)
<LOD <LOD 0.019
(<LOD–0.025)
0.027
(0.019–0.036)
4 (2014–2015) 625 21.9Table 15.15.5 footnote E
(11.8–36.9)
<LOD <LOD Table footnote F 0.046Table 15.15.5 footnote E
(0.024–0.067)
5 (2016–2017) 556 71.5
(59.1–81.3)
0.010
(0.0074–0.014)
<LOD 0.0091
(0.0061–0.012)
0.041Table 15.15.5 footnote E
(0.016–0.066)
0.067Table 15.15.5 footnote E
(0.021–0.11)
60–79 years
3 (2012–2013) 609 19.5Table 15.15.5 footnote E
(12.4–29.2)
<LOD <LOD 0.020Table 15.15.5 footnote E
(<LOD–0.027)
0.028Table 15.15.5 footnote E
(<LOD–0.041)
4 (2014–2015) 589 26.7Table 15.15.5 footnote E
(15.2–42.5)
<LOD <LOD 0.027Table 15.15.5 footnote E
(<LOD–0.040)
0.037Table 15.15.5 footnote E
(0.019–0.056)
5 (2016–2017) 567 67.9
(51.8–80.6)
0.011
(0.0078–0.015)
<LOD 0.011Table 15.15.5 footnote E
(<LOD–0.016)
0.043Table 15.15.5 footnote E
(0.024–0.062)
0.060Table 15.15.5 footnote E
(0.036–0.085)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.014, 0.014, and 0.006 μg/L, respectively.

References

15.16 Xylenes

Xylenes (CASRN 1330-20-7) are classified as volatile organic compounds (VOCs) (ATSDR, 2007; CCOHS, 2018; Environment Canada and Health Canada, 1993). The three isomers of xylene are ortho-xylene (o-xylene; CASRN 95-47-6), meta-xylene (m-xylene; CASRN 108-38-3), and para-xylene (p-xylene; CASRN 106-42-3); they differ from each other in the position of the two methyl group substitutions on the aromatic ring. The term "total xylenes" refers to all three isomers of xylene, whereas "mixed xylene" is a mixture of total xylenes and 6% to 15% ethylbenzene (CCOHS, 2018). Xylenes are primarily produced either directly or as by-products of olefin manufacturing or petroleum and coal refining (ATSDR, 2007; Environment Canada and Health Canada, 1993).

Xylene has been extensively and increasingly used in a wide range of applications as a solvent, as a replacement for benzene in the solvent components of various commercial products, and as a mixture in gasoline (ATSDR, 2007). Xylene may be widely used as a solvent in paint thinners, varnishes, lacquers, stains, concrete sealers, cleaning products, adhesives, inks, cleaning and degreasing agents, and in the production of dyes, perfumes, plastics, pharmaceuticals, and pesticides (ATSDR, 2007; Environment Canada and Health Canada, 1993; IPCS, 1997).

Xylenes are released to the environment from natural and anthropogenic sources. Xylenes have been measured in emissions from volcanoes, forest fires, and in volatiles from plants and vegetation (ATSDR, 2007; CCME, 2004). Anthropogenic sources of atmospheric xylene include volatilization of petroleum fuels and xylene-based solvents and thinners, gasoline use and motor vehicle exhaust, off-gassing from certain building materials, and consumer and automotive products (ATSDR, 2007; Environment Canada and Health Canada, 1993). Xylenes are also released to the environment in waste from manufacturing and processing facilities, from spills and accidental releases, and from the disposal of xylene-containing products (ATSDR, 2007; CCME, 2004; Environment Canada, 2014). In the past, predominant sources of releases to the atmosphere included emissions from petroleum refineries and chemical manufacturing facilities of styrene-butadiene, rubber, solvents, paints, plastics, synthetic fabric polymers, and polyesters. As new emissions-free and low-VOC technologies are implemented, along with changes in industrial and consumer use patterns and increases in fuel efficiency, releases of VOCs, including xylenes, are expected to continue to decline.

The most common route of exposure to xylenes in the general population is inhalation; exposure is attributed predominantly to indoor air because indoor air levels generally exceed outdoor levels, and because people typically spend more time indoors than out (Environment Canada and Health Canada, 1993; Health Canada, 2010a; Health Canada, 2010b; Health Canada, 2012; Health Canada, 2013). Cigarette smoking may significantly increase indoor air levels. Cigarette smoke is thought to be a major contributor to the total source of xylene exposure in smokers (ATSDR, 2007). Xylene levels in air have been shown to be higher in homes that have a garage on the property, have a higher number of occupants, have had recent renovations, and where fragrances or paint remover have been recently used (Wheeler et al., 2013). Sources of xylenes in indoor air include stored combustion equipment, various building materials, and consumer products (Won et al., 2013; Won et al., 2014; Won et al., 2015; Won and Yang, 2012). Additional exposure may result from the use of gasoline-powered engines, such as lawn mowers and outboard motors, and from ambient air, water, soil, drinking water, and food (ATSDR, 2007; IARC, 1999; Wheeler et al., 2013). Since xylenes are present as a mixture in gasoline and commercial products, the general population is expected to be exposed to xylenes primarily as a mixture rather than to individual isomers (ATSDR, 2007).

Xylene is rapidly absorbed by all routes of exposure and distributed throughout the body, primarily into adipose tissues and tissues with higher lipid content, such as the liver and brain (ATSDR, 2007; EPA, 2003; Health Canada, 2014). Elimination of xylene from blood and most tissue compartments following inhalation is generally rapid; in humans, it has an estimated half-life in the range of 1–20 hours (ATSDR, 2007). Xylene is metabolized in humans primarily by microsomal enzymes in the liver (ATSDR, 2007). The major route of excretion of absorbed xylene in the blood and body is through metabolites in urine, with minor elimination by exhalation of unchanged chemical from the lungs (ATSDR, 2007). Xylene levels in the blood are the most accurate biomarker of xylene exposure and reflect recent exposure (ATSDR, 2007; IARC, 1999).

Adverse health effects have been observed in humans and laboratory animals following xylene exposure via inhalation, ingestion, and skin contact. In humans, xylene can be irritating to the eyes, nose, throat, lungs and skin, and has been associated with symptoms of headaches, dizziness, reduced coordination, and feelings of intoxication (ATSDR, 2007; CCOHS, 2018). Acute inhalation exposure has been associated with reversible neurological symptoms; chronic exposure is associated with impaired neurological function, including cognitive and neuromuscular performance, as well as hearing deficits and dermatitis in humans (ATSDR, 2007; IARC, 1999). In humans, acute exposure to xylenes by ingestion has been associated with stomach discomfort and changes in liver and kidney function; ingestion of petroleum solvents containing xylene can be fatal (ATSDR, 2007; IPCS, 1997). Exposure to high levels of mixed xylenes (and other solvents) in humans during pregnancy has been associated with fetal toxicity and developmental effects in children at levels associated with potential maternal toxicity, such as with solvent abuse (ATSDR, 2007; EPA, 2003; IPCS, 1997). Due to inadequate data, xylene is not classifiable as to its carcinogenicity in humans according to Environment Canada and Health Canada (Group IV) and the International Agency for Research on Cancer (IARC; Group 3) (Environment Canada and Health Canada, 1993; IARC, 1999).

Under the Canadian Environmental Protection Act, 1999, Health Canada and Environment Canada concluded that xylenes are not entering the environment in quantities or under conditions that may constitute a danger to human life or health (Environment Canada and Health Canada, 1993). Xylenes are part of a larger class of VOCs that, as a group, pose environmental and health concerns because of their contributions to the formation of smog. The Government of Canada has proposed and implemented a number of actions to address VOC emissions resulting from the use of consumer and commercial products in Canada (Canada, 2009a; Canada, 2009b; Environment Canada, 2002; Environment Canada, 2013), as well as from on-road (Canada, 2003; Canada, 2015) and off-road (Canada, 2013; Canada, 2017) engines and vehicles. In 2017, Health Canada published an Indoor Air Reference Level (IARL) for xylenes (Health Canada, 2017).

Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, developed a guideline for Canadian drinking water quality that establishes a maximum acceptable concentration for total xylenes that is protective of human health, as well as an aesthetic objective for total xylenes based on its odour threshold (Health Canada 2014). The guideline was developed based on adverse neurological effects reported in experimental animals.

Xylenes were analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12–79 years in cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017). Data are presented as µg/L blood for o-xylene and the sum of m-xylene and p-xylene. Finding a measurable quantity of xylenes in blood can be an indicator of recent exposure to xylene and does not necessarily mean that an adverse health effect will occur.

Xylenes were also analyzed in indoor air from households of CHMS participants in cycle 2 (2009–2011) (Statistics Canada, 2013; Wheeler et al., 2013; Zhu et al., 2013), cycle 3 (2012–2013) (Statistics Canada, 2015), and cycle 4 (2014–2015), and in tap water from households in cycles 3 and 4. Further details on the indoor air and tap water studies are available in the Canadian Health Measures Survey (CHMS) Data User Guide: Cycle 4 (Statistics Canada, 2017). Indoor air and tap water data are available through Statistics Canada's Research Data Centres or upon request by contacting Statistics Canada at infostats@canada.ca.

Table 15.16.1: m-Xylene and p-xylene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.15.6 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2326 84.8
(78.4–89.5)
0.062
(0.050–0.079)
<LOD 0.063
(0.047–0.080)
0.20
(0.14–0.26)
0.30
(0.20–0.39)
4 (2014–2015) 2505 90.2
(83.4–94.4)
0.063
(0.053–0.075)
0.023
(<LOD–0.030)
0.061
(0.047–0.076)
0.18
(0.15–0.21)
0.26
(0.22–0.30)
5 (2016–2017) 2576 98.2
(94.0–99.5)
0.069
(0.054–0.088)
0.026
(0.019–0.033)
0.065
(0.051–0.079)
0.23
(0.16–0.30)
0.39Table 15.15.6 footnote E
(0.22–0.56)
Males, 12–79 years
3 (2012–2013) 1172 85.6
(78.6–90.6)
0.065
(0.051–0.082)
<LOD 0.062
(0.045–0.080)
0.21
(0.15–0.28)
0.34Table 15.15.6 footnote E
(0.19–0.49)
4 (2014–2015) 1239 89.3
(82.4–93.7)
0.069
(0.057–0.083)
<LOD 0.069
(0.055–0.084)
0.21
(0.15–0.27)
0.30
(0.22–0.39)
5 (2016–2017) 1281 98.0
(88.7–99.7)
0.078
(0.061–0.099)
0.029
(0.021–0.038)
0.075
(0.059–0.090)
0.26Table 15.15.6 footnote E
(0.15–0.37)
0.44Table 15.15.6 footnote E
(0.28–0.61)
Females, 12–79 years
3 (2012–2013) 1154 84.0
(76.9–89.2)
0.060
(0.047–0.078)
<LOD 0.064
(0.046–0.082)
0.19
(0.12–0.26)
0.27
(0.18–0.36)
4 (2014–2015) 1266 91.0
(83.5–95.3)
0.059
(0.049–0.069)
0.024
(<LOD–0.030)
0.056
(0.042–0.071)
0.16
(0.12–0.19)
0.21
(0.18–0.23)
5 (2016–2017) 1295 98.4
(94.4–99.6)
0.061
(0.045–0.083)
0.024Table 15.15.6 footnote E
(0.014–0.034)
0.057
(0.041–0.072)
0.17Table 15.15.6 footnote E
(0.11–0.24)
0.28Table 15.15.6 footnote E
(0.13–0.44)
12–19 years
3 (2012–2013) 701 80.6
(68.1–89.0)
0.049
(0.037–0.065)
<LOD 0.055
(0.039–0.071)
0.14Table 15.15.6 footnote E
(0.086–0.19)
0.18
(0.14–0.23)
4 (2014–2015) 709 91.1
(80.1–96.3)
0.054
(0.043–0.067)
0.024Table 15.15.6 footnote E
(<LOD–0.033)
0.055
(0.044–0.066)
0.12
(0.092–0.14)
0.16
(0.12–0.20)
5 (2016–2017) 835 96.4
(86.0–99.2)
0.055
(0.040–0.076)
0.025
(0.016–0.034)
0.058
(0.045–0.070)
0.14
(0.11–0.18)
0.17
(0.12–0.21)
20–39 years
3 (2012–2013) 500 85.2
(79.6–89.5)
0.058
(0.045–0.074)
<LOD 0.057Table 15.15.6 footnote E
(0.026–0.088)
0.16
(0.11–0.22)
0.25
(0.17–0.32)
4 (2014–2015) 596 88.8
(78.0–94.6)
0.059
(0.046–0.076)
<LOD 0.055
(0.037–0.073)
0.16
(0.12–0.19)
Table footnote F
5 (2016–2017) 591 96.6
(86.8–99.2)
0.064
(0.045–0.092)
0.020Table 15.15.6 footnote E
(0.0074–0.032)
0.063Table 15.15.6 footnote E
(0.040–0.087)
0.24
(0.17–0.31)
0.37Table 15.15.6 footnote E
(0.15–0.58)
40–59 years
3 (2012–2013) 559 87.2
(80.3–91.8)
0.074
(0.056–0.096)
<LOD 0.068
(0.052–0.084)
0.28Table 15.15.6 footnote E
(0.17–0.39)
0.42
(0.29–0.54)
4 (2014–2015) 622 90.1
(81.6–95.0)
0.067
(0.054–0.083)
<LODTable 15.15.6 footnote E
(<LOD–0.034)
0.069
(0.050–0.088)
0.21
(0.15–0.26)
0.27
(0.21–0.33)
5 (2016–2017) 569 99.6
(97.4–99.9)
0.078
(0.064–0.095)
0.031
(0.022–0.039)
0.071
(0.062–0.080)
0.26Table 15.15.6 footnote E
(0.14–0.39)
0.43Table 15.15.6 footnote E
(0.24–0.62)
60–79 years
3 (2012–2013) 566 82.4
(72.0–89.6)
0.060
(0.045–0.079)
<LOD 0.061
(0.043–0.078)
0.18
(0.15–0.21)
0.25Table 15.15.6 footnote E
(0.12–0.37)
4 (2014–2015) 578 91.9
(86.7–95.2)
0.071
(0.063–0.080)
0.025
(<LOD–0.034)
0.068
(0.057–0.079)
0.22
(0.17–0.27)
0.31
(0.23–0.39)
5 (2016–2017) 581 99.2
(88.6–99.9)
0.071
(0.055–0.092)
0.029
(0.024–0.033)
0.060
(0.045–0.075)
0.22Table 15.15.6 footnote E
(0.13–0.30)
0.41Table 15.15.6 footnote E
(0.20–0.61)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.023, 0.023, and 0.005 μg/L, respectively.

Table 15.16.2: o-Xylene — Geometric means and selected percentiles of whole blood concentrations (μg/L) for the Canadian population aged 12–79 years by age group, Canadian Health Measures Survey cycle 3 (2012–2013), cycle 4 (2014–2015), and cycle 5 (2016–2017)
Cycle n Detection Frequency
(95% CI)
GMTable 15.16.2 footnote a
(95% CI)
10th
(95% CI)
50th
(95% CI)
90th
(95% CI)
95th
(95% CI)
Total, 12–79 years
3 (2012–2013) 2336 60.0
(40.0–77.2)
<LOD 0.022Table 15.16.2 footnote E
(0.010–0.034)
0.087
(0.061–0.11)
0.11
(0.083–0.14)
4 (2014–2015) 2428 67.1
(54.7–77.6)
0.015
(0.012–0.019)
<LOD 0.016
(0.011–0.020)
0.056
(0.045–0.066)
0.082
(0.063–0.10)
5 (2016–2017) 2556 91.5
(85.7–95.1)
0.021
(0.018–0.024)
<LOD 0.020
(0.017–0.022)
0.068
(0.048–0.088)
0.10Table 15.16.2 footnote E
(0.056–0.15)
Males, 12–79 years
3 (2012–2013) 1164 61.8
(42.3–78.2)
<LOD 0.022Table 15.16.2 footnote E
(0.0097–0.033)
0.088
(0.061–0.11)
0.12
(0.075–0.16)
4 (2014–2015) 1198 69.6
(55.0–81.1)
0.017
(0.013–0.021)
<LOD 0.017
(0.012–0.023)
0.065
(0.047–0.082)
0.097Table 15.16.2 footnote E
(0.044–0.15)
5 (2016–2017) 1274 92.7
(88.8–95.3)
0.024
(0.020–0.029)
0.0072
(<LOD–0.0094)
0.021
(0.018–0.025)
0.083
(0.054–0.11)
0.14Table 15.16.2 footnote E
(0.069–0.21)
Females, 12–79 years
3 (2012–2013) 1172 58.2
(37.0–76.7)
<LOD 0.022Table 15.16.2 footnote E
(0.011–0.034)
0.081
(0.052–0.11)
0.11
(0.082–0.14)
4 (2014–2015) 1230 64.6
(52.3–75.3)
0.014
(0.011–0.017)
<LOD 0.015
(0.010–0.019)
0.049
(0.039–0.058)
0.064
(0.048–0.080)
5 (2016–2017) 1282 90.4
(79.8–95.7)
0.018
(0.015–0.023)
<LOD 0.018
(0.016–0.021)
0.051
(0.035–0.068)
0.082Table 15.16.2 footnote E
(0.037–0.13)
12–19 years
3 (2012–2013) 692 51.2Table 15.16.2 footnote E
(32.4–69.7)
<LOD Table footnote F 0.057
(0.041–0.072)
0.075
(0.053–0.098)
4 (2014–2015) 687 67.6
(49.3–81.8)
0.013
(0.0099–0.017)
<LOD 0.014
(0.0090–0.019)
0.041
(0.028–0.053)
0.052
(0.038–0.067)
5 (2016–2017) 829 89.7
(83.6–93.7)
0.018
(0.015–0.021)
<LOD 0.018
(0.014–0.022)
0.045
(0.033–0.058)
0.066
(0.042–0.089)
20–39 years
3 (2012–2013) 515 58.8
(37.2–77.5)
<LOD 0.020Table 15.16.2 footnote E
(0.0095–0.030)
0.077Table 15.16.2 footnote E
(0.036–0.12)
0.11Table 15.16.2 footnote E
(0.053–0.17)
4 (2014–2015) 580 56.4
(38.8–72.4)
0.012
(0.0090–0.017)
<LOD 0.012Table 15.16.2 footnote E
(<LOD–0.018)
0.046
(0.036–0.057)
Table footnote F
5 (2016–2017) 584 88.7
(74.5–95.4)
0.020
(0.015–0.025)
<LOD 0.019
(0.015–0.023)
0.069
(0.047–0.090)
0.097Table 15.16.2 footnote E
(0.048–0.15)
40–59 years
3 (2012–2013) 565 66.6
(43.5–83.8)
0.022Table 15.16.2 footnote E
(0.014–0.034)
<LOD 0.029Table 15.16.2 footnote E
(0.012–0.045)
0.099
(0.075–0.12)
0.13
(0.095–0.17)
4 (2014–2015) 604 73.1
(62.2–81.7)
0.017
(0.014–0.021)
<LOD 0.018
(0.012–0.023)
0.060
(0.049–0.071)
0.087
(0.063–0.11)
5 (2016–2017) 565 94.7
(88.5–97.6)
0.023
(0.019–0.026)
0.0075
(<LOD–0.010)
0.020
(0.015–0.024)
0.066Table 15.16.2 footnote E
(0.039–0.093)
0.13Table 15.16.2 footnote E
(0.048–0.21)
60–79 years
3 (2012–2013) 564 55.1
(35.8–72.9)
0.016Table 15.16.2 footnote E
(0.010–0.023)
<LOD 0.016Table 15.16.2 footnote E
(<LOD–0.027)
0.076
(0.055–0.098)
0.10Table 15.16.2 footnote E
(0.030–0.17)
4 (2014–2015) 557 74.0
(66.2–80.5)
0.018
(0.016–0.021)
<LOD 0.019
(0.015–0.023)
0.077
(0.058–0.096)
0.096
(0.070–0.12)
5 (2016–2017) 578 92.0
(87.6–94.9)
0.022
(0.018–0.027)
0.0069
(<LOD–0.0094)
0.021
(0.018–0.023)
0.080
(0.054–0.11)
0.13Table 15.16.2 footnote E
(0.063–0.20)

CI: confidence interval; GM: geometric mean; LOD: limit of detection

Note: The LODs for cycles 3, 4, and 5 are 0.0090, 0.0090, and 0.006 μg/L, respectively.

References

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