Page 7 - Fourth Report on Human Biomonitoring of Environmental Chemicals in Canada

15 Summaries and results for volatile organic compounds

15.1 Benzene and benzene metabolites

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, 2009f). It was first isolated and synthesized in the early 1800s and presently is commercially recovered from both coal and petroleum sources for industrial applications (ATSDR, 2007c).

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, 2007c; Environment Canada and Health Canada, 1993c). Benzene is also used at various stages in the manufacturing of synthetic fibres, rubbers, lubricants, dyes, detergents, drugs, and pesticides (ATSDR, 2007c).

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, 1993c). 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, 1993c). 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, 2009f). Natural sources are generally considered to contribute less benzene to the environment than anthropogenic sources (Environment Canada and Health Canada, 1993c).

The general population is exposed to benzene mainly through inhalation of ambient air; higher exposures occur particularly in areas of heavy vehicle traffic and at gasoline service stations, and from tobacco smoke (ATSDR, 2007c). Exposure to benzene in ambient air accounts for an estimated 98% to 99% of total benzene intake for Canadian non-smokers (Health Canada, 2009f). 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). Various marketplace products containing benzene can also contribute to its presence in indoor air (Environment Canada and Health Canada, 1993c). Although benzene has been detected in tap water and in certain foods and beverages, these are not considered to constitute major sources of exposure for the general population (ATSDR, 2007c; Health Canada, 2009f).

Following inhalation, benzene is readily absorbed into the blood and is distributed throughout the body, concentrating in adipose tissue (EPA, 2002). In the lung and liver, benzene is metabolized into several reactive metabolites including benzene oxide (EPA, 2002; McHale et al., 2012). Benzene metabolism can branch into several alternative metabolic pathways: spontaneous rearrangement of benzene oxide 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, 2007c). 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 benzene exposure. Exposure to benzene can be hematotoxic in humans and laboratory animals, with bone marrow 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). Epidemiologic studies and case 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, 1993c; IARC, 2012b). 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, 2007c; 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). In Canada, regulations have been put in place to limit the concentration of benzene in gasoline as well as emissions from vehicles (Canada, 1997; Environment Canada, 2014). Benzene is listed on Schedule 1, List of Toxic Substances, under the Canadian Environmental Protection Act, 1999 (CEPA 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, 1993c). In 2000-2001, the Canadian Council of Ministers of the Environment endorsed the Canada-wide standard for benzene requiring industry reduction of total benzene emissions and use of best management practices (CCME, 2000b; 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 included as a prohibited ingredient on the List of Prohibited and Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient Hotlist or simply the Hotlist). The Hotlist is an administrative tool that Health Canada uses to communicate to manufacturers and others that certain substances, when present in a cosmetic, may contravene the general prohibition found in section 16 of the Food and Drugs Act or a provision of the Cosmetic Regulations (Canada, 1985a; Health Canada, 2015b).

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 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, 2013c).

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 endpoints, and that is considered protective of both cancer and non-cancer effects (Health Canada, 2009f). 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, 2013h). On the basis of a low but non-negligible cancer risk at indoor exposure levels, the guidance recommends that individuals take actions to reduce exposure to benzene indoors as much as possible. In particular, exposure reduction strategies have been recommended targeting 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) and cycle 4 (2014-2015) participants aged 12-79 years. Benzene metabolites, t,t-MA and S-PMA, were analyzed in the urine of CHMS cycle 2 (2009-2011) and cycle 3 (2012-2013) participants aged 3 to 79 years. Data are presented as µg/L blood for benzene and µg/L and µg/g creatinine for t,t-MA and S-PMA. Finding a measurable amount of benzene in blood or t,t-MA and S-PMA in urine can be an indicator of exposure to benzene and does not necessarily mean that an adverse health effect will occur.

Benzene was also analyzed in indoor air from households of CHMS participants in cycle 2 (2009-2011) (Statistics Canada, 2012; Wheeler et al., 2013; Zhu et al., 2013), 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@statcan.gc.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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2488	12.58	0.036 (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	7.48	0.034^{Footnote E} (0.024-0.050)	0.0093^{Footnote E} (<LOD-0.013)	0.033^{Footnote E} (0.017-0.049)	0.14 (0.090-0.19)	0.21 (0.16-0.26)
Males, 12-79 years
3 (2012-2013)	1245	11.57	0.037 (0.026-0.052)	<LOD	0.040 (0.030-0.049)	0.15 (0.13-0.18)	0.24 (0.18-0.30)
4 (2014-2015)	1164	6.44	0.037 (0.026-0.054)	0.0097^{Footnote E} (<LOD-0.015)	0.036^{Footnote E} (0.019-0.054)	0.16 (0.10-0.21)	0.23 (0.15-0.31)
Females, 12-79 years
3 (2012-2013)	1243	13.60	0.035^{Footnote E} (0.024-0.051)	<LOD	0.038 (0.028-0.049)	0.17^{Footnote E} (0.093-0.24)	0.23^{Footnote E} (0.11-0.35)
4 (2014-2015)	1190	8.49	0.032^{Footnote E} (0.021-0.048)	0.0090^{Footnote E} (<LOD-0.013)	0.030^{Footnote E} (0.015-0.045)	0.13^{Footnote E} (0.071-0.19)	0.19 (0.14-0.25)
12-19 years
3 (2012-2013)	750	14.00	0.028 (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	9.65	0.028^{Footnote E} (0.019-0.041)	0.0087^{Footnote E} (<LOD-0.014)	0.029^{Footnote E} (0.013-0.045)	0.087 (0.068-0.11)	0.12 (0.074-0.16)
20-39 years
3 (2012-2013)	548	10.40	0.037^{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	6.69	0.033^{Footnote E} (0.021-0.051)	0.0097^{Footnote E} (<LOD-0.014)	0.031^{Footnote E} (0.0097-0.052)	0.12 (0.074-0.16)	0.17^{Footnote E} (0.11-0.24)
40-59 years
3 (2012-2013)	598	8.70	0.040 (0.030-0.055)	<LOD	0.039 (0.028-0.050)	0.23 (0.16-0.31)	0.40^{Footnote E} (0.24-0.56)
4 (2014-2015)	575	6.26	0.041^{Footnote E} (0.027-0.062)	0.010^{Footnote E} (<LOD-0.015)	0.037^{Footnote E} (0.014-0.060)	0.18 (0.13-0.22)	0.29^{Footnote E} (0.18-0.40)
60-79 years
3 (2012-2013)	592	16.72	0.031^{Footnote E} (0.021-0.047)	<LOD	0.038 (0.026-0.051)	0.13 (0.085-0.17)	0.20 (0.16-0.24)
4 (2014-2015)	548	6.93	0.031 (0.023-0.042)	0.0084^{Footnote E} (<LOD-0.013)	0.030 (0.021-0.039)	0.13 (0.085-0.17)	0.24^{Footnote E} (0.15-0.33)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution.

Table 15.1.2 - S-Phenylmercapturic acid (S-PMA) - Geometric means and selected percentiles of urine concentrations (μg/L) for the Canadian population aged 3-79 years by age group, Canadian Health Measures Survey cycle 2 (2009-2011), cycle 3 (2012-2013) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 3-79 years
2 (2009-2011)	2525	22.10	0.20 (0.18-0.23)	<LOD	0.12 (0.095-0.15)	1.3 (0.85-1.7)	3.5 (2.5-4.5)
3 (2012-2013)	2472	34.67	0.17 (0.14-0.21)	<LOD	0.10^{Footnote E} (<LOD-0.16)	^{Footnote F}	3.4 (2.3-4.5)
4 (2014-2015)	2484	36.59	0.17 (0.14-0.19)	<LOD	0.12 (0.10-0.14)	1.7^{Footnote E} (0.86-2.5)	3.4 (2.1-4.6)
Males, 3-79 years
2 (2009-2011)	1267	20.21	0.23 (0.20-0.26)	<LOD	0.13 (0.10-0.16)	^{Footnote F}	3.9^{Footnote E} (2.5-5.4)
3 (2012-2013)	1223	31.07	0.20 (0.16-0.25)	<LOD	0.19^{Footnote E} (0.080-0.30)	1.9^{Footnote E} (0.51-3.3)	4.0 (2.7-5.3)
4 (2014-2015)	1246	34.43	0.17 (0.13-0.23)	<LOD	0.12 (0.093-0.15)	1.6^{Footnote E} (0.65-2.6)	3.1^{Footnote E} (1.1-5.0)
Females, 3-79 years
2 (2009-2011)	1258	24.01	0.18 (0.15-0.22)	<LOD	0.11 (<LOD-0.14)	1.1^{Footnote E} (0.66-1.6)	2.5^{Footnote E} (0.89-4.1)
3 (2012-2013)	1249	38.19	0.14 (0.10-0.19)	<LOD	0.099 (<LOD-0.12)	^{Footnote F}	3.3^{Footnote E} (1.4-5.2)
4 (2014-2015)	1238	38.77	0.16 (0.12-0.20)	<LOD	0.12 (0.089-0.14)	^{Footnote F}	4.2^{Footnote E} (2.3-6.1)
3-5 years
2 (2009-2011)	507	20.32	0.15 (0.13-0.17)	<LOD	0.12 (0.094-0.14)	0.40 (0.29-0.52)	0.64^{Footnote E} (0.40-0.88)
3 (2012-2013)	491	28.51	0.11 (0.10-0.12)	<LOD	0.099 (0.096-0.10)	0.32 (0.26-0.37)	0.51^{Footnote E} (0.30-0.72)
4 (2014-2015)	487	34.50	0.11 (0.091-0.13)	<LOD	0.11 (0.087-0.13)	0.43 (0.32-0.55)	0.56 (0.41-0.71)
6-11 years
2 (2009-2011)	511	25.24	0.14 (0.11-0.17)	<LOD	0.099 (0.083-0.12)	0.38 (0.28-0.49)	0.58^{Footnote E} (0.33-0.82)
3 (2012-2013)	491	38.90	0.099 (0.084-0.12)	<LOD	0.099 (0.092-0.11)	0.31 (0.23-0.39)	0.41 (0.35-0.47)
4 (2014-2015)	501	42.51	-	<LOD	0.11 (0.095-0.12)	0.36 (0.28-0.45)	0.49 (0.37-0.62)
12-19 years
2 (2009-2011)	506	18.97	0.17 (0.15-0.20)	<LOD	0.13 (0.094-0.16)	0.62 (0.45-0.79)	1.1^{Footnote E} (0.53-1.6)
3 (2012-2013)	497	32.19	0.14 (0.11-0.19)	<LOD	0.10^{Footnote E} (<LOD-0.15)	^{Footnote F}	2.3^{Footnote E} (0.74-4.0)
4 (2014-2015)	488	33.81	0.12 (0.11-0.13)	<LOD	0.11 (0.093-0.12)	0.65^{Footnote E} (0.40-0.90)	0.80 (0.60-0.99)
20-39 years
2 (2009-2011)	355	19.44	0.21 (0.17-0.27)	<LOD	0.12 (<LOD-0.16)	1.4 (1.1-1.8)	3.0^{Footnote E} (1.5-4.5)
3 (2012-2013)	345	35.07	0.20^{Footnote E} (0.14-0.30)	<LOD	0.17^{Footnote E} (<LOD-0.29)	^{Footnote F}	3.3^{Footnote E} (1.4-5.3)
4 (2014-2015)	353	30.59	0.19 (0.14-0.27)	<LOD	0.13 (0.093-0.17)	^{Footnote F}	3.3^{Footnote E} (2.0-4.6)
40-59 years
2 (2009-2011)	359	25.91	0.24 (0.18-0.30)	<LOD	0.13^{Footnote E} (<LOD-0.20)	2.9^{Footnote E} (1.1-4.7)	5.2^{Footnote E} (3.2-7.3)
3 (2012-2013)	306	35.62	0.20^{Footnote E} (0.14-0.30)	<LOD	0.17^{Footnote E} (<LOD-0.29)	^{Footnote F}	3.4^{Footnote E} (1.8-5.0)
4 (2014-2015)	309	38.83	0.20 (0.15-0.27)	<LOD	0.12 (0.084-0.16)	3.1^{Footnote E} (1.1-5.2)	5.4^{Footnote E} (2.9-8.0)
60-79 years
2 (2009-2011)	287	23.69	0.19 (0.15-0.23)	<LOD	0.12 (0.094-0.15)	1.1^{Footnote E} (0.57-1.7)	3.4^{Footnote E} (1.3-5.4)
3 (2012-2013)	342	39.77	0.14 (0.11-0.18)	<LOD	0.093 (0.087-0.099)	^{Footnote F}	5.1^{Footnote E} (2.0-8.3)
4 (2014-2015)	346	39.02	0.14 (0.12-0.18)	<LOD	0.10 (<LOD-0.14)	1.6^{Footnote E} (0.44-2.8)	3.2^{Footnote E} (1.3-5.1)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

Table 15.1.3 - S-Phenylmercapturic acid (S-PMA) (creatinine adjusted) - Geometric means and selected percentiles of urine concentrations (μg/g creatinine) for the Canadian population aged 3-79 years by age group, Canadian Health Measures Survey cycle 2 (2009-2011), cycle 3 (2012-2013) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 3-79 years
2 (2009-2011)	2515	22.10	0.20 (0.17-0.24)	<LOD	0.19 (0.12-0.26)	1.2^{Footnote E} (0.62-1.8)	3.1 (2.0-4.2)
3 (2012-2013)	2471	34.67	0.18 (0.15-0.22)	<LOD	0.14 (<LOD-0.16)	1.4^{Footnote E} (0.86-2.0)	2.9 (1.9-4.0)
4 (2014-2015)	2484	36.59	0.15 (0.13-0.17)	<LOD	0.11 (0.090-0.13)	1.6 (1.0-2.1)	2.7 (2.3-3.0)
Males, 3-79 years
2 (2009-2011)	1263	20.21	0.19 (0.16-0.23)	<LOD	0.13^{Footnote E} (0.061-0.20)	1.8^{Footnote E} (0.84-2.8)	3.0^{Footnote E} (1.0-5.0)
3 (2012-2013)	1223	31.07	0.17 (0.14-0.21)	<LOD	0.12 (0.089-0.16)	1.4 (0.94-1.9)	2.2^{Footnote E} (1.2-3.3)
4 (2014-2015)	1246	34.43	0.14 (0.11-0.18)	<LOD	0.099 (0.084-0.11)	1.4^{Footnote E} (0.38-2.4)	2.3^{Footnote E} (1.4-3.3)
Females, 3-79 years
2 (2009-2011)	1252	24.01	0.20 (0.16-0.26)	<LOD	0.19 (<LOD-0.24)	0.91^{Footnote E} (0.57-1.2)	3.1^{Footnote E} (1.1-5.2)
3 (2012-2013)	1248	38.19	0.18 (0.14-0.24)	<LOD	0.14 (<LOD-0.16)	^{Footnote F}	3.4^{Footnote E} (1.7-5.1)
4 (2014-2015)	1238	38.77	0.17 (0.13-0.21)	<LOD	0.13 (0.096-0.15)	1.7^{Footnote E} (<LOD-2.8)	3.1^{Footnote E} (1.6-4.6)
3-5 years
2 (2009-2011)	506	20.32	0.26 (0.23-0.29)	<LOD	0.29 (0.19-0.39)	0.69 (0.56-0.82)	0.91 (0.71-1.1)
3 (2012-2013)	490	28.51	0.22 (0.20-0.24)	<LOD	0.20 (0.16-0.24)	0.52 (0.39-0.65)	0.79^{Footnote E} (0.50-1.1)
4 (2014-2015)	487	34.50	0.19 (0.17-0.22)	<LOD	0.18 (0.16-0.21)	0.54 (0.44-0.64)	0.76 (0.62-0.89)
6-11 years
2 (2009-2011)	509	25.24	0.15 (0.13-0.19)	<LOD	0.17^{Footnote E} (0.057-0.28)	0.46 (0.31-0.61)	0.60 (0.40-0.80)
3 (2012-2013)	491	38.90	0.13 (0.11-0.15)	<LOD	0.13 (0.10-0.15)	0.32 (0.27-0.37)	0.41 (0.36-0.45)
4 (2014-2015)	501	42.51	-	<LOD	0.12 (0.10-0.14)	0.33 (0.25-0.42)	0.46 (0.39-0.54)
12-19 years
2 (2009-2011)	504	18.97	0.13 (0.11-0.15)	<LOD	0.10 (0.091-0.11)	0.50 (0.34-0.66)	0.78^{Footnote E} (0.50-1.1)
3 (2012-2013)	497	32.19	0.11 (0.087-0.14)	<LOD	0.092 (<LOD-0.11)	^{Footnote F}	1.3^{Footnote E} (0.59-2.0)
4 (2014-2015)	488	33.81	0.089 (0.080-0.10)	<LOD	0.077 (0.065-0.088)	0.33 (0.24-0.43)	0.52^{Footnote E} (0.26-0.78)
20-39 years
2 (2009-2011)	353	19.44	0.19 (0.14-0.25)	<LOD	^{Footnote F}	1.6^{Footnote E} (0.59-2.6)	2.9^{Footnote E} (1.7-4.1)
3 (2012-2013)	345	35.07	0.15 (0.11-0.21)	<LOD	0.12 (<LOD-0.16)	1.1^{Footnote E} (<LOD-1.8)	1.7^{Footnote E} (0.86-2.6)
4 (2014-2015)	353	30.59	0.16 (0.11-0.23)	<LOD	0.13 (0.096-0.16)	1.9^{Footnote E} (0.93-2.9)	2.4 (1.7-3.1)
40-59 years
2 (2009-2011)	357	25.91	0.23 (0.17-0.31)	<LOD	0.19 (<LOD-0.24)	^{Footnote F}	4.2^{Footnote E} (1.5-7.0)
3 (2012-2013)	306	35.62	0.24 (0.17-0.34)	<LOD	0.17 (<LOD-0.23)	2.0^{Footnote E} (<LOD-3.5)	3.5^{Footnote E} (1.8-5.3)
4 (2014-2015)	309	38.83	0.18 (0.13-0.24)	<LOD	0.10 (0.068-0.13)	2.5 (1.7-3.4)	3.6^{Footnote E} (1.3-5.8)
60-79 years
2 (2009-2011)	286	23.69	0.21 (0.17-0.27)	<LOD	0.19 (0.15-0.23)	1.2^{Footnote E} (0.55-1.9)	2.9^{Footnote E} (1.3-4.5)
3 (2012-2013)	342	39.77	0.17 (0.13-0.23)	<LOD	0.12 (0.080-0.16)	2.1^{Footnote E} (<LOD-3.5)	3.5^{Footnote E} (2.2-4.9)
4 (2014-2015)	346	39.02	0.14 (0.11-0.19)	<LOD	0.098 (<LOD-0.13)	^{Footnote F}	3.2^{Footnote E} (1.6-4.7)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

Table 15.1.4 - trans,trans-Muconic acid (t,t-MA) - Geometric means and selected percentiles of urine concentrations (μg/L) for the Canadian population aged 3-79 years by age group, Canadian Health Measures Survey cycle 2 (2009-2011), cycle 3 (2012-2013) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 3-79 years
2 (2009-2011)	2523	0.20	64 (57-71)	15 (12-19)	59 (52-66)	330 (260-390)	500 (330-680)
3 (2012-2013)	2492	0	56 (47-67)	14 (11-16)	53 (41-65)	250 (160-340)	400 (290-510)
4 (2014-2015)	2514	0	67 (61-74)	15 (12-18)	57 (53-61)	350 (260-450)	670^{Footnote E} (410-930)
Males, 3-79 years
2 (2009-2011)	1267	0.24	68 (58-81)	19 (13-25)	66 (54-78)	340 (260-420)	480 (330-630)
3 (2012-2013)	1231	0	64 (53-78)	17 (14-20)	59 (45-73)	260^{Footnote E} (140-380)	400^{Footnote E} (140-650)
4 (2014-2015)	1257	0	72 (62-84)	19 (16-23)	58 (50-66)	340 (220-450)	540^{Footnote E} (280-790)
Females, 3-79 years
2 (2009-2011)	1256	0.16	59 (51-70)	13 (9.2-17)	56 (47-64)	320 (220-420)	610^{Footnote E} (330-890)
3 (2012-2013)	1261	0	49 (41-60)	11 (7.2-14)	46 (34-59)	230^{Footnote E} (120-340)	430 (290-580)
4 (2014-2015)	1257	0	62 (51-74)	12 (8.3-15)	54 (41-66)	370 (240-510)	730^{Footnote E} (460-1000)
3-5 years
2 (2009-2011)	506	0.40	75 (63-90)	20 (15-24)	68 (52-83)	380^{Footnote E} (220-540)	670 (510-840)
3 (2012-2013)	489	0	65 (57-75)	14 (12-17)	51 (41-61)	440 (390-490)	730^{Footnote E} (440-1000)
4 (2014-2015)	494	0	73 (58-93)	16^{Footnote E} (9.1-22)	63 (46-79)	380^{Footnote E} (230-520)	750^{Footnote E} (400-1100)
6-11 years
2 (2009-2011)	511	0.20	71 (57-87)	17 (13-21)	63 (41-85)	380^{Footnote E} (240-510)	540 (360-720)
3 (2012-2013)	496	0	61 (49-75)	12 (7.3-16)	55 (39-71)	330^{Footnote E} (200-470)	740^{Footnote E} (220-1300)
4 (2014-2015)	508	0	75 (60-93)	14 (9.6-17)	61 (50-73)	500 (340-660)	820^{Footnote E} (470-1200)
12-19 years
2 (2009-2011)	506	0	75 (61-92)	15^{Footnote E} (8.4-21)	66 (47-85)	380 (290-480)	560 (440-680)
3 (2012-2013)	506	0	65 (48-88)	13 (8.3-18)	61 (45-77)	360^{Footnote E} (220-510)	670^{Footnote E} (350-1000)
4 (2014-2015)	495	0	74 (66-83)	17 (13-20)	71 (55-87)	350 (230-460)	740^{Footnote E} (430-1100)
20-39 years
2 (2009-2011)	355	0.56	62 (48-81)	13^{Footnote E} (6.3-19)	70 (54-86)	310^{Footnote E} (120-510)	610^{Footnote E} (300-910)
3 (2012-2013)	347	0	66 (46-95)	15^{Footnote E} (9.0-22)	66^{Footnote E} (40-92)	270^{Footnote E} (140-400)	380^{Footnote E} (160-590)
4 (2014-2015)	356	0	75 (57-100)	17^{Footnote E} (10-24)	58 (45-70)	680^{Footnote E} (190-1200)	790^{Footnote E} (450-1100)
40-59 years
2 (2009-2011)	359	0	65 (54-80)	17 (14-20)	57 (41-73)	310^{Footnote E} (170-460)	470^{Footnote E} (200-750)
3 (2012-2013)	307	0	50 (39-65)	15^{Footnote E} (8.4-21)	47 (32-61)	160^{Footnote E} (73-240)	360^{Footnote E} (130-590)
4 (2014-2015)	309	0	60 (52-70)	16 (11-21)	53 (40-66)	250 (170-330)	410^{Footnote E} (220-600)
60-79 years
2 (2009-2011)	286	0	54 (43-67)	14^{Footnote E} (7.6-21)	52 (37-67)	240^{Footnote E} (120-370)	400 (300-500)
3 (2012-2013)	347	0	50 (40-62)	10^{Footnote E} (4.5-16)	44 (34-55)	260^{Footnote E} (70-460)	550^{Footnote E} (170-930)
4 (2014-2015)	352	0	59 (51-67)	14 (11-18)	55 (46-64)	240 (160-320)	390 (280-510)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution.

Table 15.1.5 - trans,trans-Muconic acid (t,t-MA) (creatinine adjusted) - Geometric means and selected percentiles of urine concentrations (μg/g creatinine) for the Canadian population aged 3-79 years by age group, Canadian Health Measures Survey cycle 2 (2009-2011), cycle 3 (2012-2013) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 3-79 years
2 (2009-2011)	2513	0.20	63 (58-70)	19 (16-21)	54 (48-60)	280 (230-340)	450 (370-520)
3 (2012-2013)	2491	0	58 (51-66)	19 (17-21)	51 (43-58)	220 (160-280)	390 (270-510)
4 (2014-2015)	2514	0	60 (54-68)	17 (15-18)	52 (45-59)	280 (220-340)	460 (340-580)
Males, 3-79 years
2 (2009-2011)	1263	0.24	59 (50-69)	17 (15-19)	52 (40-63)	230 (150-320)	380 (280-480)
3 (2012-2013)	1231	0	54 (48-60)	19 (16-21)	51 (44-57)	160^{Footnote E} (97-210)	290^{Footnote E} (110-470)
4 (2014-2015)	1257	0	57 (48-68)	17 (15-18)	49 (39-60)	250^{Footnote E} (160-350)	400^{Footnote E} (250-560)
Females, 3-79 years
2 (2009-2011)	1250	0.16	69 (61-77)	20 (17-23)	55 (48-63)	320 (240-400)	490 (320-650)
3 (2012-2013)	1260	0	63 (54-74)	19 (16-22)	51 (39-62)	270 (190-340)	460 (300-630)
4 (2014-2015)	1257	0	64 (56-74)	16 (14-19)	54 (45-62)	310 (250-380)	490 (350-620)
3-5 years
2 (2009-2011)	505	0.40	130 (110-160)	36 (31-41)	110 (87-130)	590 (420-750)	990^{Footnote E} (580-1400)
3 (2012-2013)	488	0	130 (110-150)	34 (31-37)	87 (70-100)	910 (650-1200)	1500^{Footnote E} (810-2100)
4 (2014-2015)	494	0	130 (110-160)	35 (32-38)	100^{Footnote E} (63-140)	760 (510-1000)	1300^{Footnote E} (690-1900)
6-11 years
2 (2009-2011)	509	0.20	82 (68-99)	24 (20-28)	69 (52-87)	380 (290-470)	490 (360-620)
3 (2012-2013)	496	0	78 (65-93)	21 (18-23)	65 (55-75)	380^{Footnote E} (220-530)	720^{Footnote E} (260-1200)
4 (2014-2015)	508	0	81 (67-98)	21 (17-25)	61 (46-76)	470^{Footnote E} (240-700)	760 (600-910)
12-19 years
2 (2009-2011)	504	0	57 (48-69)	18 (15-20)	43 (29-57)	320 (230-410)	410 (340-490)
3 (2012-2013)	506	0	49 (40-61)	15 (13-17)	38 (27-49)	230^{Footnote E} (140-310)	450 (290-600)
4 (2014-2015)	495	0	54 (47-63)	15 (12-18)	47 (36-58)	210 (140-280)	450 (330-560)
20-39 years
2 (2009-2011)	353	0.56	55 (46-66)	16 (14-19)	48 (36-60)	270^{Footnote E} (120-420)	430 (300-570)
3 (2012-2013)	347	0	50 (38-66)	16 (10-21)	46^{Footnote E} (22-70)	160 (120-200)	240^{Footnote E} (90-390)
4 (2014-2015)	356	0	61 (47-81)	17 (14-21)	53 (37-68)	400^{Footnote E} (200-600)	580^{Footnote E} (320-840)
40-59 years
2 (2009-2011)	357	0	66 (53-82)	19 (14-23)	54 (37-71)	270 (200-340)	^{Footnote F}
3 (2012-2013)	307	0	59 (47-75)	22 (19-24)	54 (41-66)	190^{Footnote E} (95-280)	290^{Footnote E} (120-450)
4 (2014-2015)	309	0	55 (49-62)	16 (13-19)	49 (41-57)	190 (150-230)	270 (190-350)
60-79 years
2 (2009-2011)	285	0	63 (54-73)	20 (18-23)	55 (44-65)	220^{Footnote E} (120-330)	400^{Footnote E} (210-590)
3 (2012-2013)	347	0	57 (48-70)	20 (18-23)	43 (32-53)	^{Footnote F}	490^{Footnote E} (220-760)
4 (2014-2015)	352	0	57 (47-69)	16 (13-19)	50 (41-59)	240^{Footnote E} (130-350)	300 (230-370)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

15.2 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, 2010a; IARC, 2000). The quantity of ethylbenzene manufactured in Canada has remained relatively stable since 1999 (Environment and Climate Change Canada and Health Canada, 2016c).

Major uses of ethylbenzene include manufacturing of styrene and synthetic rubber (ATSDR, 2010a; Environment and Climate Change Canada and Health Canada, 2016c; 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, 2010a). Ethylbenzene is a constituent of asphalt, naphtha, and automotive and aviation fuels, including gasoline that typically contains about 2% ethylbenzene by weight (ATSDR, 2010a). Commercial mixed xylenes contain ethylbenzene at levels up to 25% and, as such, ethylbenzene may be present in some paints, including spray paints and primers, lacquers, printing inks, insecticides, and solvents containing xylenes (ATSDR, 2010a; Environment and Climate Change Canada and Health Canada, 2016c; 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, 2010a; Environment and Climate Change Canada and Health Canada, 2016c; 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, 2016c).

For the general population, most exposure to ethylbenzene originates from the inhalation of indoor air (Environment and Climate Change Canada and Health Canada, 2016c; Health Canada, 2007c). Inside residences, ethylbenzene levels in air have been shown to be higher for homes with an attached garage, with a higher number of occupants, with recent renovations, and in which fragrances and paint remover have been recently 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 unlikely a significant source (Environment and Climate Change Canada and Health Canada, 2016c; Health Canada, 2010j). Various other marketplace products containing ethylbenzene can also contribute to its presence in indoor air (ATSDR, 2010a; Environment and Climate Change Canada and Health Canada, 2016c). Although ethylbenzene has been detected in outdoor air, drinking water, soil, and food, these are not considered to constitute major sources of exposure for the general population (Health Canada, 2007c).

Following inhalation, oral, and dermal exposures, ethylbenzene is readily absorbed and distributed throughout the body (ATSDR, 2010a; IARC, 2000). Absorption of ethylbenzene by inhalation is approximately 49% to 64%, in humans (ATSDR, 2010a). 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 fewer than 1 to 25 hours (ATSDR, 2010a). Following oral exposure, absorption of ethylbenzene is approximately 72% to 92% in laboratory animals and elimination is rapid, occurring predominantly via urinary excretion (ATSDR, 2010a). In contrast, 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, 2010a).

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, 2010a; Environment and Climate Change Canada and Health Canada, 2016c). Acute inhalation exposure has been generally associated with reversible neurological symptoms and respiratory tract irritation whereas chronic exposure has been associated with impaired neurological function, including cognitive and neuromuscular performance (ATSDR, 2010a; Environment and Climate Change Canada and Health Canada, 2016c). 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, 2010a; Environment and Climate Change Canada and Health Canada, 2016c). In laboratory animals, chronic exposure to high levels of ethylbenzene in air and via the oral route has been associated with kidney and liver damage, some minor developmental effects, and effects in blood, pituitary, thyroid, and respiratory tissues (ATSDR, 2010a; Environment and Climate Change Canada and Health Canada, 2016c). Ethylbenzene is classified as possibly carcinogenic to humans (Group 2B carcinogen) 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).

Health Canada and Environment Canada published a final screening assessment on ethylbenzene in 2016 and have concluded that it is not entering the environment in a quantity or concentration or under conditions that constitute or may constitute a danger in Canada to human life or health (Environment and Climate Change Canada and Health Canada, 2016c).

The Government of Canada has also taken a number of actions to address VOCs, a large class of compounds that includes ethylbenzene. As a class, they are environmental and health concerns because of their contribution 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, 2013c).

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, 2014e). The guideline was developed based on cancer and non-cancer endpoints in the liver, kidney, and pituitary gland of experimental animals (Health Canada, 2014e).

Ethylbenzene was analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12-79 years in cycle 3 (2012-2013) and cycle 4 (2014-2015). 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, 2012; Wheeler et al., 2013), 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@statcan.gc.ca.

Table 15.2.1 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2441	17.90	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	11.90	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)
Males, 12-79 years
3 (2012-2013)	1212	17.49	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	11.62	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)
Females, 12-79 years
3 (2012-2013)	1229	18.31	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	12.16	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)
12-19 years
3 (2012-2013)	731	19.84	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	15.37	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)
20-39 years
3 (2012-2013)	532	17.29	0.026 (0.019-0.035)	<LOD	0.026^{Footnote E} (0.012-0.041)	0.077^{Footnote E} (0.040-0.11)	0.12^{Footnote E} (0.058-0.17)
4 (2014-2015)	596	12.75	0.024 (0.019-0.032)	<LOD	0.023 (0.016-0.029)	0.062^{Footnote E} (0.034-0.089)	^{Footnote F}
40-59 years
3 (2012-2013)	591	14.89	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	8.36	0.029 (0.023-0.036)	0.012^{Footnote E} (<LOD-0.016)	0.025 (0.017-0.033)	0.098 (0.070-0.13)	0.12 (0.10-0.14)
60-79 years
3 (2012-2013)	587	19.08	0.025 (0.019-0.032)	<LOD	0.024 (0.016-0.032)	0.079 (0.064-0.094)	0.12^{Footnote E} (0.062-0.17)
4 (2014-2015)	578	10.55	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)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

15.3 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, 2010b; IARC, 2002).

Styrene has been synthetically produced since the early 19^th 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, 2010b; IARC, 2002). Commercial styrene contains several 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, 1993d). Styrene-based polymer materials are used in the manufacturing of a wide range of products, most of which also contain a small amount of unlinked styrene monomer (ATSDR, 2010b; Environment Canada and Health Canada, 1993d). 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, 2010b; Environment Canada and Health Canada, 1993d).

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, 1993d; ATSDR, 2010b). 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, 2010b; Environment Canada and Health Canada, 1993d).

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 (ATSDR, 2010b; Environment Canada and Health Canada, 1993d). 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, 1993d; 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, 2010b; Environment Canada and Health Canada, 1993d). Further, it is not uncommon for short-term inhalation exposures to styrene to occur as a result of indoor air releases from new building materials made with polymer resins, synthetic rubbers, laminated materials, and from fresh adhesives and surface coatings. 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 packaged food in polystyrene containers (ATSDR, 2010b; Genualdi et al., 2014). Intake of styrene from drinking water is generally negligible (Environment Canada and Health Canada, 1993d). 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, 2010b; Environment Canada and Health Canada, 1993d). Following oral exposure in laboratory animals, styrene absorption was rapid and complete with distribution to the kidney, liver, pancreas, adipose tissue and, to a lesser extent, the stomach, and small and large intestines (ATSDR, 2010b). Styrene absorbed into the body was rapidly eliminated from all tissues within 1 to 3 days (ATSDR, 2010b). Half-lives are estimated to range between 1 and 13 hours depending on the phase of elimination; in adipose tissue, an elimination half-life of 2 to 5 days has been estimated (ATSDR, 2010b). In humans, approximately 97% of the styrene absorbed is excreted as urinary metabolites, with the remainder eliminated unchanged in expired air (ATSDR, 2010b; Environment Canada and Health Canada, 1993d). 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, 2010b; Environment Canada and Health Canada, 1993d). 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, 2010b; Environment Canada and Health Canada, 1993d). In laboratory animals, following oral exposure styrene was rapidly excreted in urine with 90% eliminated within 24 hours, and less than 2% in the feces (ATSDR, 2010b). The most reliable biomarkers of recent exposure to styrene are measurements of styrene in blood, urine, and breath (ATSDR, 2010b).

Acute exposure to styrene is irritating to the eyes, nose, and throat, and induces dermatitis (ATSDR, 2010b; 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, 2010b; Environment Canada and Health Canada, 1993d). 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, 2010b; ATSDR, 2012c; IARC, 2002). Whether chronic styrene exposure results in permanent damage to the nervous system in humans has not been determined (ATSDR, 2010b). 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, 2010b; Environment Canada and Health Canada, 1993d; 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, 2010b; 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, 1993d; 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). Recently, the U.S. National Toxicology Program listed styrene as reasonably anticipated to be a human carcinogen based on human cancer studies, laboratory animal studies, and supporting mechanistic data (ATSDR, 2011; NTP, 2016).

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, 1993d). Styrene is also part of a larger class of VOCs that, as a group, are environmental and health concerns because of their contribution 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, 2013c). 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) and cycle 4 (2014-2015). 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), and in tap water from households in cycle 3 and cycle 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@statcan.gc.ca.

Table 15.3.1 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2063	7.61	0.043^{Footnote E} (0.029-0.062)	^{Footnote F}	0.043 (0.030-0.055)	0.12 (0.076-0.16)	0.17^{Footnote E} (0.10-0.23)
4 (2014-2015)	2527	3.09	0.055 (0.043-0.070)	0.026^{Footnote E} (0.013-0.040)	0.058 (0.047-0.069)	0.11 (0.094-0.13)	0.14 (0.12-0.15)
Males, 12-79 years
3 (2012-2013)	1036	6.95	0.043^{Footnote E} (0.029-0.064)	^{Footnote F}	0.045 (0.033-0.057)	0.12 (0.079-0.15)	0.17^{Footnote E} (0.099-0.24)
4 (2014-2015)	1251	3.28	0.056 (0.042-0.075)	0.026^{Footnote E} (<LOD-0.042)	0.063 (0.049-0.077)	0.12 (0.097-0.14)	0.14 (0.12-0.16)
Females, 12-79 years
3 (2012-2013)	1027	8.28	0.042^{Footnote E} (0.028-0.061)	^{Footnote F}	0.041 (0.028-0.055)	0.11^{Footnote E} (0.062-0.17)	0.16^{Footnote E} (0.092-0.23)
4 (2014-2015)	1276	2.90	0.053 (0.044-0.065)	0.027^{Footnote E} (0.015-0.038)	0.055 (0.046-0.065)	0.10 (0.078-0.12)	0.13 (0.10-0.15)
12-19 years
3 (2012-2013)	626	8.47	0.037^{Footnote E} (0.024-0.057)	^{Footnote F}	0.040 (0.029-0.052)	0.094^{Footnote E} (0.029-0.16)	0.15^{Footnote E} (0.063-0.24)
4 (2014-2015)	713	3.23	0.053 (0.041-0.068)	0.027^{Footnote E} (0.014-0.041)	0.058 (0.045-0.070)	0.097 (0.086-0.11)	0.10 (0.087-0.11)
20-39 years
3 (2012-2013)	435	7.36	0.043^{Footnote E} (0.029-0.065)	<LOD	0.043^{Footnote E} (0.024-0.061)	0.12^{Footnote E} (0.055-0.18)	0.18^{Footnote E} (0.10-0.26)
4 (2014-2015)	600	2.83	0.055 (0.043-0.070)	0.029^{Footnote E} (0.014-0.044)	0.057 (0.047-0.068)	0.11 (0.085-0.13)	0.12 (0.10-0.15)
40-59 years
3 (2012-2013)	493	5.68	0.045^{Footnote E} (0.031-0.066)	0.016^{Footnote E} (<LOD-0.026)	0.044 (0.032-0.056)	0.13 (0.090-0.16)	0.18^{Footnote E} (0.11-0.25)
4 (2014-2015)	625	3.84	0.056 (0.042-0.075)	0.025^{Footnote E} (<LOD-0.040)	0.064 (0.049-0.079)	0.12 (0.099-0.15)	0.15 (0.12-0.17)
60-79 years
3 (2012-2013)	509	8.64	0.041^{Footnote E} (0.027-0.063)	^{Footnote F}	0.044 (0.029-0.058)	0.11 (0.069-0.15)	0.14^{Footnote E} (0.049-0.24)
4 (2014-2015)	589	2.38	0.053 (0.043-0.065)	0.025^{Footnote E} (0.012-0.038)	0.053 (0.042-0.064)	0.11 (0.086-0.13)	0.14 (0.11-0.17)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

15.4 Tetrachloroethylene (perchloroethylene)

Tetrachloroethylene (CASRN 127-18-4), commonly known as perchloroethylene, is a colourless liquid classified as a volatile organic compound (Canada, 2011a; Canada, 2011b; Environment Canada and Health Canada, 1993e; 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-20^th century, tetrachloroethylene 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, 2011a; Canada, 2011b; 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 is being phased out by 2030 (IARC, 2014; UNEP, 2007). In Canada, tetrachloroethylene production ceased in 1992 and, 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, 1993e; Health Canada, 2015c).

Releases of tetrachloroethylene are mainly to the atmosphere by evaporative losses from anthropogenic sources (ATSDR, 1997b; Environment Canada and Health Canada, 1993e). 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, automotive products, and other consumer products containing tetracholroethylene (Environment Canada and Health Canada, 1993e). 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, 1993e). Exposure can also occur during the use of consumer products containing tetrachloroethylene, and from ambient air and food (ATSDR, 1997b; Environment Canada and Health Canada, 1993e). Living near a dry-cleaning facility may also increase the potential for exposure (ATSDR, 1997b; CDC, 2009; IARC, 2014).

Tetrachloroethylene is rapidly absorbed into the blood and is distributed throughout the body with some concentration in adipose tissue (ATSDR, 1997b; Environment Canada and Health Canada, 1993e; 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 within minutes and hours 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, 30 to 40, and 55 hours, respectively (ATSDR, 1997b). 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, 1997b; 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, 1997). At very high concentrations, acute inhalation and oral exposure to tetrachloroethylene can induce atrophy of olfactory nerves, tremors, and central nervous system depression, as well as kidney and liver dysfunction in laboratory animals; these symptoms are similar to those observed in humans following accidental poisonings and solvent abuse (ATSDR, 1997b; Environment Canada and Health Canada, 1993e). Tetrachloroethylene exposure is also associated with narcotic and anesthetic effects increasing in severity with increasing exposure (ATSDR, 1997b; Environment Canada and Health Canada, 1993e; EPA, 2012). These neurological symptoms may be reversible following cessation of acute exposure; however, chronic exposures may result in more persistent neurological impairments (ATSDR, 1997b; Environment Canada and Health Canada, 1993e; IARC, 2014). Multiple cancer sites of interest have been evaluated by the International Agency for Research (IARC) on Cancer Expert Working Group and 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, 1993e; IARC, 2014).

The Government of Canada conducted a scientific assessment on 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, 1993e). 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, 2011c; Canada, 2011d). 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, 2011d; Environment Canada, 2013d). Tetrachloroethylene is included as a prohibited ingredient on the List of Prohibited and Restricted Cosmetic Ingredients (more commonly referred to as the Cosmetic Ingredient Hotlist or simply the Hotlist). The Hotlist is an administrative tool that Health Canada uses to communicate to manufacturers and others that certain substances, when present in a cosmetic, may contravene the general prohibition found in section 16 of the Food and Drugs Act or a provision of the Cosmetic Regulations (Canada, 1985a; Health Canada, 2015b). In addition, 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, 2015c). 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) and cycle 4 (2014-2015). 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) 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@statcan.gc.ca.

Table 15.4.1 - Tetrachloroethylene (Perchloroethylene) - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2453	60.82	-	<LOD	<LOD	0.10 (0.067-0.14)	0.17^{Footnote E} (0.10-0.23)
4 (2014-2015)	2527	70.32	-	<LOD	<LOD	0.066^{Footnote E} (0.022-0.11)	^{Footnote F}
Males, 12-79 years
3 (2012-2013)	1228	58.96	-	<LOD	<LOD	0.13 (0.086-0.17)	0.19 (0.13-0.25)
4 (2014-2015)	1251	70.02	-	<LOD	<LOD	^{Footnote F}	^{Footnote F}
Females, 12-79 years
3 (2012-2013)	1225	62.69	-	<LOD	<LOD	0.096^{Footnote E} (0.060-0.13)	0.13^{Footnote E} (0.039-0.22)
4 (2014-2015)	1276	70.61	-	<LOD	<LOD	0.068^{Footnote E} (<LOD-0.12)	^{Footnote F}
12-19 years
3 (2012-2013)	739	60.76	-	<LOD	<LOD	^{Footnote F}	^{Footnote F}
4 (2014-2015)	713	77.00	-	<LOD	<LOD	0.042^{Footnote E} (<LOD-0.065)	^{Footnote F}
20-39 years
3 (2012-2013)	543	60.04	-	<LOD	<LOD	0.093^{Footnote E} (0.052-0.13)	0.15^{Footnote E} (0.080-0.23)
4 (2014-2015)	600	68.50	-	<LOD	<LOD	^{Footnote F}	^{Footnote F}
40-59 years
3 (2012-2013)	587	65.08	-	<LOD	<LOD	0.10^{Footnote E} (0.058-0.14)	0.13 (0.089-0.17)
4 (2014-2015)	625	70.08	-	<LOD	<LOD	0.061^{Footnote E} (<LOD-0.10)	^{Footnote F}
60-79 years
3 (2012-2013)	584	57.36	-	<LOD	<LOD	0.16^{Footnote E} (0.062-0.25)	^{Footnote F}
4 (2014-2015)	589	64.35	-	<LOD	<LOD	0.088^{Footnote E} (0.028-0.15)	^{Footnote F}
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

15.5 Toluene

Toluene (CASRN 108-88-3) is a colourless liquid and volatile organic compound (VOC). It is produced commercially, primarily through the conversion of petroleum to gasoline and other fuels or recovered as a by-product in the coke oven and styrene-manufacturing industries (ATSDR, 2000; Environment Canada and Health Canada, 1992).

Toluene is used widely as an industrial solvent and an intermediate in the production of a variety of chemicals. Major uses of toluene have included the manufacture of benzene, benzene derivatives, trinitrotoluene and toluene diisocyanate, and in the blending of gasoline fuels as octane boosters (ATSDR, 2000; 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, 2000; Environment Canada and Health Canada, 1992; Health Canada, 2016b). 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 (ATSDR, 2000; Environment Canada and Health Canada, 1992). Anthropogenic sources of atmospheric toluene include primarily the volatilization of petroleum fuels, toluene-based solvents and thinners, motor vehicle exhaust, and the off-gassing of toluene from some building materials, consumer, and automotive products (ATSDR, 2000; 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, 2000; CCME, 2004a; Environment Canada and Health Canada, 1992).

The general population is exposed to toluene mainly through the inhalation of indoor air (Health Canada, 2011d). Cigarette smoking may significantly increase exposure and, in smokers, inhalation of cigarette smoke is expected to be a major contributor to the total toluene exposure (ATSDR, 2000; Health Canada, 2011d; Health Canada, 2012g). 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). Toluene is also found in tobacco smoke, and regular smoking in the home is a significant predictor of toluene in indoor air (Health Canada, 2012g). 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, 2014e).

Following inhalation, toluene is readily absorbed and distributed throughout the body (ATSDR, 2000; 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, 2000). Up to 20% of absorbed toluene is exhaled unchanged and less than 1% is excreted unchanged in the urine (ATSDR, 2000; Donald et al., 1991). The elimination of toluene following inhalation has half-lives ranging from less than 3 minutes to 12 hours in blood and from 0.5 to 3 days in subcutaneous adipose tissues of humans (ATSDR, 2000). Toluene levels in blood are the most accurate biomarker of toluene exposure and are reflective of recent exposure (ATSDR, 2000; 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, 2013a; Health Canada, 2011d; Health Canada, 2012g; IARC, 1999a). Acute inhalation exposure has been generally associated with reversible neurological symptoms whereas chronic exposure is associated with impaired neurological function including cognitive and neuromuscular performance, as well as negative effects on colour vision and hearing (ATSDR, 2000; CCOHS, 2013b; CDC, 2009; Health Canada, 2011d; IARC, 1999a). 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, 2000; 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, 2000; Bowen and Hannigan, 2006; Donald et al., 1991; Yücel et al., 2008). Toluene carcinogenicity to humans is not classifiable according to the International Agency for Research on Cancer (Group 3) and the U.S. Environmental Protection Agency (Group D) (EPA, 2005; IARC, 1999a).

Under the Canadian Environmental Protection Act, 1999 (CEPA 1999), Health Canada and Environment Canada concluded that at current environmental concentrations, toluene is not a concern for human life or health (Environment Canada and Health Canada, 1992). Toluene is also part of a larger class of VOCs that, as a group, are environmental and health concerns because of their contribution 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, 2013c).

In 2011, Health Canada released a residential indoor air quality guideline for both short- and long-term exposure to toluene (Health Canada, 2011d). 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, 2014e). The guideline was developed based on several neurological endpoints reported in human occupational studies.

Toluene was analyzed in the whole blood of Canadian Health Measures Survey participants aged 12 to 79 years in cycle 3 (2012-2013) and cycle 4 (2014-2015). 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, 2012; Wheeler et al., 2013), 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@statcan.gc.ca.

Table 15.5.1 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2449	0.69	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	0.08	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)
Males, 12-79 years
3 (2012-2013)	1224	0.65	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	0.17	0.13 (0.10-0.18)	0.044^{Footnote E} (0.023-0.065)	0.12 (0.085-0.15)	0.46 (0.30-0.61)	0.65 (0.41-0.88)
Females, 12-79 years
3 (2012-2013)	1225	0.73	0.093 (0.081-0.11)	0.037 (0.034-0.041)	0.077 (0.064-0.089)	0.35 (0.24-0.46)	0.55^{Footnote E} (0.34-0.76)
4 (2014-2015)	1202	0	0.11 (0.086-0.15)	0.043 (0.030-0.055)	0.10^{Footnote E} (0.058-0.14)	0.37^{Footnote E} (0.17-0.57)	0.53 (0.43-0.64)
12-19 years
3 (2012-2013)	732	0.55	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	0	0.096 (0.070-0.13)	0.039 (0.028-0.050)	0.097 (0.061-0.13)	0.22^{Footnote E} (0.14-0.31)	0.30^{Footnote E} (0.17-0.44)
20-39 years
3 (2012-2013)	533	0.94	0.089 (0.069-0.11)	0.036 (0.028-0.045)	0.074 (0.050-0.098)	0.29^{Footnote E} (0.16-0.43)	0.42^{Footnote E} (0.23-0.61)
4 (2014-2015)	574	0	0.12 (0.094-0.16)	0.047^{Footnote E} (0.027-0.067)	0.12^{Footnote E} (0.076-0.17)	0.30^{Footnote E} (0.19-0.41)	0.46 (0.30-0.61)
40-59 years
3 (2012-2013)	594	0.51	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	0.17	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)
60-79 years
3 (2012-2013)	590	0.85	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	0.18	0.12 (0.089-0.16)	0.038^{Footnote E} (0.023-0.054)	0.099^{Footnote E} (0.061-0.14)	0.49 (0.34-0.64)	0.70 (0.46-0.94)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution.

15.6 Trichloroethylene

Trichloroethylene (CASRN 79-01-6) is a colourless liquid classified as a volatile organic compound. It has been produced commercially by chlorination of acetylene and ethylene since the 1920s (ATSDR, 1997c; IARC, 1995). There has been a general decline in demand for trichloroethylene over the years (Health Canada, 2005b; 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, 2005b; IARC, 2014). In Canada, production of trichloroethylene stopped in 1985 (Health Canada, 2005b). Since then, it continues to be imported for use primarily as a solvent in the vapour-degreasing and cold-cleaning of metal parts and, in smaller amounts, in dry-cleaning operations, specialty paints and paint removers, and various other household products (Environment Canada, 2013e; Environment Canada, 2013f; Health Canada, 2005b). 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, 1997c; Environment Canada, 2013f). Although the majority of anthropogenic releases enter the atmosphere, production, use, and disposal of trichloroethylene and trichloroethylene-containing products can also result in releases to the environment via wastewater. A small amount of trichloroethylene is produced naturally in the environment by marine algae (Abrahamsson et al., 1995).

The most common exposure route to trichloroethylene 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, 1993f). Canadians may also be exposed to trichloroethylene through its presence in drinking water, air, and food (Health Canada, 2005b).

Following all routes of exposure, trichloroethylene is rapidly and nearly completely absorbed into the blood and distributed throughout the body (ATSDR, 1997c; Environment Canada and Health Canada, 1993f; EPA, 2011). Absorbed trichloroethylene is rapidly distributed mainly to the brain, kidney, liver, muscle, and adipose tissue (ATSDR, 1997c). Trichloroethylene is metabolized in the kidney, liver, and lungs forming the major metabolites trichloroacetic acid (TCA) and trichloroethanol (TCOH) (ATSDR, 1997c; EPA, 2011). Absorbed trichloroethylene is rapidly eliminated from the body, within minutes and hours, via exhalation of trichloroethylene and urinary excretion of the metabolites along with minimal amounts of unchanged trichloroethylene (ATSDR, 1997c; EPA, 2011). The most reliable biomarker of recent exposure to trichloroethylene is its measurement in blood and breath (ATSDR, 1997c; IARC, 1995). Measurements of the metabolites TCA and TCOH in blood or urine are less reliable because of intra-individual differences in urinary concentrations and a lack of specificity for trichloroethylene exposure (ATSDR, 1997c; 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 of membranes (ATSDR, 1997c; Health Canada, 2005b; IARC, 1995). Trichloroethylene exposure is also associated with narcotic and anesthetic effects increasing in severity with increasing exposure (Environment Canada and Health Canada, 1993f; IARC, 1995). These neurological symptoms may be reversible following cessation of acute exposure; however, chronic exposures may result in more persistent neurological impairments (ATSDR, 1997c; Environment Canada and Health Canada, 1993f; EPA, 2011). Recently, the International Agency for Research on Cancer updated its classification for trichloroethylene to Group 1 carcinogenic to humans, on the basis of new and sufficient evidence for cancer of the kidney in humans, with strong support from studies in laboratory animals (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 on the impact of trichloroethylene exposure on humans and the environment and concluded that it may enter the environment in quantities or under conditions that may constitute a danger in Canada to human life or health as per criteria set out under the Canadian Environmental Protection Act, 1999 (CEPA 1999) (Environment Canada and Health Canada, 1993f). 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, 2013d). Improvements have also been implemented in the commercial dry-cleaning industry to prevent and minimize releases of dry-cleaning solvents, particularly trichloroethylene and tetrachloroethylene (Canada, 2011c; Canada, 2011d; IARC, 2014). The current guideline for Canadian drinking water quality, developed by Health Canada, in collaboration with the Federal-Provincial-Territorial Committee on Drinking Water, establishes the maximum acceptable concentration for trichloroethylene in drinking water (Health Canada, 2005b). 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) and cycle 4 (2014-2015). 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), 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@statcan.gc.ca.

Table 15.6.1 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2474	99.51	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	2527	99.49	-	<LOD	<LOD	<LOD	<LOD
Males, 12-79 years
3 (2012-2013)	1240	99.35	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	1251	99.20	-	<LOD	<LOD	<LOD	<LOD
Females, 12-79 years
3 (2012-2013)	1234	99.68	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	1276	99.76	-	<LOD	<LOD	<LOD	<LOD
12-19 years
3 (2012-2013)	746	99.73	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	713	100	-	<LOD	<LOD	<LOD	<LOD
20-39 years
3 (2012-2013)	543	99.63	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	600	98.83	-	<LOD	<LOD	<LOD	<LOD
40-59 years
3 (2012-2013)	594	99.33	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	625	99.52	-	<LOD	<LOD	<LOD	<LOD
60-79 years
3 (2012-2013)	591	99.32	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	589	99.49	-	<LOD	<LOD	<LOD	<LOD
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated.

15.7 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, 1999c; CDC, 2009; Health Canada, 2006c). 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, 2006c). In cycle 4 of the Canadian Health Measures Survey (CHMS), four THMs were measured: bromodichloromethane, dibromochloromethane, bromoform (tribromomethane), and chloroform (trichloromethane). Each of these compounds consists of three halogen groups attached to a single carbon atom and are classified as volatile organic compounds (VOCs) (CCME, 1999c). Chloroform is the most common THM and the most frequently measured disinfection by-product in chlorinated drinking water in Canada (ATSDR, 2005b; Health Canada, 2006c).

Table 15.7.1 - Trihalomethanes measured in the Canadian Health Measures Survey cycle 3 (2012-2013) and cycle 4 (2014-2015)
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, 1999b; 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, 2006c). In Canada, the use of chloroform as an anaesthetic has been discontinued and its use in dentifrices, liniments, and antitussives has been banned (CCME, 1999c; 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, 2006c. Bromoform is used as a solvent in the synthesis of pharmaceuticals and in fire-resistant chemicals, as well as gauge fluid used in the aircraft and shipbuilding industries (Health Canada, 2006c.

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, 1999b; ATSDR, 2005). Anthropogenic sources are generally considered to be larger contributors of THMs in the environment than natural ones. 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, 1993g). 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, 2006c). 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, 2006c). Effluent wastewaters are disinfected to protect downstream municipal water supplies, recreational waters, and shellfish-growing areas from bacterial contamination and other microorganisms causing water-borne disease (Environment Canada and Health Canada, 1993g). In addition to drinking water, disinfection effluents, and cooling waters, anthropogenic sources of THMs include chemical manufacturing plants and industrial sites, swimming pools, hot tubs, and water parks (ATSDR, 2005; CCME, 1999c; Health Canada, 2006c).

The general population is exposed to THMs primarily by drinking chlorinated water (CDC, 2009; Environment Canada and Health Canada, 2001; Health Canada, 2006c). Exposure also occurs through inhalation during showering and bathing, and by skin absorption during bathing and swimming (CDC, 2009; Health Canada, 2006c). Minor exposures may occur from the consumption of food and beverages (Health Canada, 2006c). 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, 2006c; WHO, 2004). THMs are well absorbed following both oral and inhalation exposure, with dermal exposure as another potentially significant route of exposure (ATSDR, 1989; Health Canada, 2006c; IPCS, 2000; WHO, 2004). Estimated half-lives for THMs in the body generally range from 1.5 hours to 6 hours; about 95% of absorbed bromodichloromethane is eliminated from the body in 8 hours (ATSDR, 1989; Health Canada, 2006c; WHO, 2004). Absorbed THMs 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, 2006c; 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, and acute inhalation exposure has been associated with reddening of the face (Health Canada, 2006c; IPCS, 2000; WHO, 2004). Acute high-level inhalation and oral exposures to these disinfection by-products in laboratory animals induce general narcotic and anesthetic effects increasing in severity with exposure level and are generally reversible following cessation of exposure (Health Canada, 2006c; IPCS, 2000; WHO, 2004). Some studies in laboratory animals indicate that THMs containing bromine, such as bromodichloromethane, may be more toxic than chloroform and other chlorine-containing disinfection by-products (Health Canada, 2006c). Chronic exposures to THMs in drinking water are weakly and inconsistently associated with cancers of the liver, kidney, colon, rectal, brain, pancreas, and bladder (Health Canada, 2006c IPCS, 2000; WHO, 2004). 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, 2006c; WHO, 2004). 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, 1993g). However, there is 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, 2012c; 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, 2006c). 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, 2006c). 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) and cycle 4 (2014-2015) 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.

Table 15.7.2 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2499	98.88	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	2527	96.91	-	<LOD	<LOD	<LOD	<LOD
Males, 12-79 years
3 (2012-2013)	1245	98.96	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	1251	97.36	-	<LOD	<LOD	<LOD	<LOD
Females, 12-79 years
3 (2012-2013)	1254	98.80	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	1276	96.47	-	<LOD	<LOD	<LOD	<LOD
12-19 years
3 (2012-2013)	744	98.12	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	713	96.35	-	<LOD	<LOD	<LOD	<LOD
20-39 years
3 (2012-2013)	556	98.92	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	600	97.67	-	<LOD	<LOD	<LOD	<LOD
40-59 years
3 (2012-2013)	595	99.66	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	625	96.00	-	<LOD	<LOD	<LOD	<LOD
60-79 years
3 (2012-2013)	604	99.01	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	589	97.79	-	<LOD	<LOD	<LOD	<LOD
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated.

Table 15.7.3 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2527	97.07	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	2499	96.24	-	<LOD	<LOD	<LOD	<LOD
Males, 12-79 years
3 (2012-2013)	1263	96.52	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	1233	96.76	-	<LOD	<LOD	<LOD	<LOD
Females, 12-79 years
3 (2012-2013)	1264	97.63	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	1266	95.73	-	<LOD	<LOD	<LOD	<LOD
12-19 years
3 (2012-2013)	757	96.83	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	704	96.45	-	<LOD	<LOD	<LOD	<LOD
20-39 years
3 (2012-2013)	557	97.13	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	596	96.14	-	<LOD	<LOD	<LOD	<LOD
40-59 years
3 (2012-2013)	604	98.01	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	617	95.62	-	<LOD	<LOD	<LOD	<LOD
60-79 years
3 (2012-2013)	609	96.39	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	582	96.74	-	<LOD	<LOD	<LOD	<LOD
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated.

Table 15.7.4 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2496	94.79	-	<LOD	<LOD	<LOD	0.010^{Footnote E} (<LOD-0.015)
4 (2014-2015)	2527	97.39	-	<LOD	<LOD	<LOD	<LOD
Males, 12-79 years
3 (2012-2013)	1244	95.02	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	1251	97.44	-	<LOD	<LOD	<LOD	<LOD
Females, 12-79 years
3 (2012-2013)	1252	94.57	-	<LOD	<LOD	<LOD	<LOD^{Footnote E} (<LOD-0.013)
4 (2014-2015)	1276	97.34	-	<LOD	<LOD	<LOD	<LOD
12-19 years
3 (2012-2013)	744	94.49	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	713	97.05	-	<LOD	<LOD	<LOD	<LOD
20-39 years
3 (2012-2013)	554	94.40	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	600	97.67	-	<LOD	<LOD	<LOD	<LOD
40-59 years
3 (2012-2013)	595	96.47	-	<LOD	<LOD	<LOD	<LOD
4 (2014-2015)	625	97.60	-	<LOD	<LOD	<LOD	<LOD
60-79 years
3 (2012-2013)	603	93.86	-	<LOD	<LOD	<LOD	^{Footnote F}
4 (2014-2015)	589	97.28	-	<LOD	<LOD	<LOD	<LOD
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

Table 15.7.5 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2527	77.44	-	<LOD	<LOD	0.021 (0.016-0.026)	0.029 (0.019-0.038)
4 (2014-2015)	2527	75.78	-	<LOD	<LOD	0.028^{Footnote E} (<LOD-0.043)	0.043^{Footnote E} (0.022-0.064)
Males, 12-79 years
3 (2012-2013)	1263	77.51	-	<LOD	<LOD	0.021 (0.015-0.027)	0.035^{Footnote E} (0.018-0.052)
4 (2014-2015)	1251	77.22	-	<LOD	<LOD	^{Footnote F}	0.046^{Footnote E} (0.022-0.069)
Females, 12-79 years
3 (2012-2013)	1264	77.37	-	<LOD	<LOD	0.021 (0.016-0.027)	0.028 (0.019-0.037)
4 (2014-2015)	1276	74.37	-	<LOD	<LOD	0.030^{Footnote E} (0.016-0.045)	0.039^{Footnote E} (0.016-0.062)
12-19 years
3 (2012-2013)	757	77.81	-	<LOD	<LOD	0.020^{Footnote E} (<LOD-0.028)	0.031^{Footnote E} (<LOD-0.049)
4 (2014-2015)	713	75.32	-	<LOD	<LOD	0.028^{Footnote E} (0.017-0.038)	0.040^{Footnote E} (0.015-0.066)
20-39 years
3 (2012-2013)	557	76.48	-	<LOD	<LOD	0.023 (0.016-0.029)	0.036^{Footnote E} (0.015-0.058)
4 (2014-2015)	600	75.33	-	<LOD	<LOD	0.030^{Footnote E} (0.016-0.045)	^{Footnote F}
40-59 years
3 (2012-2013)	604	78.81	-	<LOD	<LOD	0.019 (<LOD-0.025)	0.027 (0.019-0.036)
4 (2014-2015)	625	76.16	-	<LOD	<LOD	^{Footnote F}	0.046^{Footnote E} (0.024-0.067)
60-79 years
3 (2012-2013)	609	76.52	-	<LOD	<LOD	0.020^{Footnote E} (<LOD-0.027)	0.028^{Footnote E} (<LOD-0.041)
4 (2014-2015)	589	76.40	-	<LOD	<LOD	0.027^{Footnote E} (<LOD-0.040)	0.037^{Footnote E} (0.019-0.056)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

15.8 Xylenes

Xylenes (CASRN 1330-20-7) are classified as volatile organic compounds (VOCs) (ATSDR, 2007d; CCOHS, 2013; Environment Canada and Health Canada, 1993h). 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 ethylbenzene (6% to 15%) (CCOHS, 2013). Xylenes are primarily produced either directly or as by-products of petroleum and coal refining and as by-products of olefin manufacturing (ATSDR, 2007d; Environment Canada and Health Canada, 1993h).

Xylenes have 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, 2007d). Xylenes 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, 2007d; Environment Canada and Health Canada, 1993h; 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, 2007d; CCME, 2004b). Anthropogenic sources of atmospheric xylenes include volatilization of petroleum fuels and xylene-based solvents and thinners, gasoline use and motor vehicle exhaust, and the off-gassing of xylenes from some building materials, and consumer and automotive products containing xylenes (ATSDR, 2007d; Environment Canada and Health Canada, 1993h). 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, 2007d; CCME, 2004b; 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 being implemented, and changes in industrial and consumer use patterns and increases in fuel efficiency occur, releases of VOCs, including xylenes, are expected to continue their decline.

The general population is exposed to xylenes mainly through inhalation of indoor air (Environment Canada and Health Canada, 1993h). Cigarette smoking may significantly increase levels in indoor air and, in smokers, inhalation of cigarette smoke is expected to be a major contribution to the total source of xylene exposure (ATSDR, 2007d). In addition to smoking, xylene levels in air have been shown to be higher for homes with a garage on the property, with a higher number of occupants, with recent renovations, and in which fragrances and paint remover have been recently used (Wheeler et al., 2013). Additional exposure may result from the use of consumer products containing xylenes, 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, 2007d; IARC, 1999a; Wheeler et al., 2013). As xylenes are present as a mixture in gasoline and commercial products, the general population is expected to be primarily exposed to xylenes as a mixture, not to the separate xylene isomers (ATSDR, 2007d).

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

Adverse health effects have been observed in humans and laboratory animals following xylene exposure via inhalation, ingestion, and dermal routes. In humans, xylenes 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, 2007d; CCOHS, 2013). Acute inhalation exposure has been associated with reversible neurological symptoms whereas 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, 1999a). 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 can be fatal (ATSDR, 2007d; 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 in solvent abuse (ATSDR, 2007d; EPA, 2003; IPCS, 1997). Xylenes are not classifiable as to their carcinogenicity in humans according to Environment Canada and Health Canada (Group IV), the International Agency for Research on Cancer (Group 3) and the U.S. Environmental Protection Agency (Group D) (Environment Canada and Health Canada, 1993h; EPA, 2003; IARC, 1999a).

Under the Canadian Environmental Protection Act, 1999 (CEPA 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, 1993h). Xylenes also part of a larger class of VOCs that, as a group, are environmental and health concerns because of their contribution 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, 2013c).

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 xylenes that is protective of human health, as well as an aesthetic objective for xylenes based on their odour thresholds (Health Canada 2014).

Xylenes were analyzed in the whole blood of Canadian Health Measures Survey (CHMS) participants aged 12-79 years in cycle 3 (2012-2013) and cycle 4 (2014-2015). Data are presented as µg/L blood for o-xylene and the sum of m-xylene and p-xylene. Finding a measurable amount 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, 2012; Wheeler et al., 2013), 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@statcan.gc.ca.

Table 15.8.1 - m-Xylene & 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2326	14.53	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	7.27	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)
Males, 12-79 years
3 (2012-2013)	1172	13.31	0.065 (0.051-0.082)	<LOD	0.062 (0.045-0.080)	0.21 (0.15-0.28)	0.34^{Footnote E} (0.19-0.49)
4 (2014-2015)	1239	6.86	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)
Females, 12-79 years
3 (2012-2013)	1154	15.77	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	7.66	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)
12-19 years
3 (2012-2013)	701	16.83	0.049 (0.037-0.065)	<LOD	0.055 (0.039-0.071)	0.14^{Footnote E} (0.086-0.19)	0.18 (0.14-0.23)
4 (2014-2015)	709	7.90	0.054 (0.043-0.067)	0.024^{Footnote E} (<LOD-0.033)	0.055 (0.044-0.066)	0.12 (0.092-0.14)	0.16 (0.12-0.20)
20-39 years
3 (2012-2013)	500	14.00	0.058 (0.045-0.074)	<LOD	0.057^{Footnote E} (0.026-0.088)	0.16 (0.11-0.22)	0.25 (0.17-0.32)
4 (2014-2015)	596	7.21	0.059 (0.046-0.076)	<LOD	0.055 (0.037-0.073)	0.16 (0.12-0.19)	^{Footnote F}
40-59 years
3 (2012-2013)	559	11.99	0.074 (0.056-0.096)	<LOD	0.068 (0.052-0.084)	0.28^{Footnote E} (0.17-0.39)	0.42 (0.29-0.54)
4 (2014-2015)	622	6.43	0.067 (0.054-0.083)	<LOD^{Footnote E} (<LOD-0.034)	0.069 (0.050-0.088)	0.21 (0.15-0.26)	0.27 (0.21-0.33)
60-79 years
3 (2012-2013)	566	14.66	0.060 (0.045-0.079)	<LOD	0.061 (0.043-0.078)	0.18 (0.15-0.21)	0.25^{Footnote E} (0.12-0.37)
4 (2014-2015)	578	7.44	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)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

Table 15.8.2 - 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) and cycle 4 (2014-2015).
Cycle	n	%<LOD^{Footnote a}	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 12-79 years
3 (2012-2013)	2336	41.05	-	<LOD	0.022^{Footnote E} (0.010-0.034)	0.087 (0.061-0.11)	0.11 (0.083-0.14)
4 (2014-2015)	2428	29.57	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)
Males, 12-79 years
3 (2012-2013)	1164	40.55	-	<LOD	0.022^{Footnote E} (0.0097-0.033)	0.088 (0.061-0.11)	0.12 (0.075-0.16)
4 (2014-2015)	1198	27.71	0.017 (0.013-0.021)	<LOD	0.017 (0.012-0.023)	0.065 (0.047-0.082)	0.097^{Footnote E} (0.044-0.15)
Females, 12-79 years
3 (2012-2013)	1172	41.55	-	<LOD	0.022^{Footnote E} (0.011-0.034)	0.081 (0.052-0.11)	0.11 (0.082-0.14)
4 (2014-2015)	1230	31.38	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)
12-19 years
3 (2012-2013)	692	43.93	-	<LOD	^{Footnote F}	0.057 (0.041-0.072)	0.075 (0.053-0.098)
4 (2014-2015)	687	32.17	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)
20-39 years
3 (2012-2013)	515	42.14	-	<LOD	0.020^{Footnote E} (0.0095-0.030)	0.077^{Footnote E} (0.036-0.12)	0.11^{Footnote E} (0.053-0.17)
4 (2014-2015)	580	32.41	0.012 (0.0090-0.017)	<LOD	0.012^{Footnote E} (<LOD-0.018)	0.046 (0.036-0.057)	^{Footnote F}
40-59 years
3 (2012-2013)	565	38.94	0.022^{Footnote E} (0.014-0.034)	<LOD	0.029^{Footnote E} (0.012-0.045)	0.099 (0.075-0.12)	0.13 (0.095-0.17)
4 (2014-2015)	604	26.49	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)
60-79 years
3 (2012-2013)	564	38.65	0.016^{Footnote E} (0.010-0.023)	<LOD	0.016^{Footnote E} (<LOD-0.027)	0.076 (0.055-0.098)	0.10^{Footnote E} (0.030-0.17)
4 (2014-2015)	557	26.75	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)
^a If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated. ^E Use data with caution. ^F Data is too unreliable to be published.

Appendix A: Limits of detection

Laboratory analyses of environmental chemicals and creatinine were performed at analytical laboratories within Health Canada, l'Institut national de santé publique du Québec, and the ALS Laboratory Group. Laboratories developed standardized operating procedures for the analytical methods used to measure environmental chemicals or their metabolites in biological samples. The limit of detection (LOD) is defined as the lowest concentration of the analyte whose analytical response is measured to be greater than the noise level with 99% confidence and evaluated using U.S. Environmental Protection Agency methodology (EPA, 2015).

Limits of Detection
Chemical	Cycle 1	Cycle 2	Cycle 3	Cycle 4
Acrylamide
Acrylamide haemoglobin (Hb) adduct	-	-	11 pmol/g Hb	11 pmol/g Hb
Glycidamide haemoglobin (Hb) adduct	-	-	23 pmol/g Hb	23 pmol/g Hb
Environmental phenols
Bisphenol A	0.2 µg/L	0.2 µg/L	0.23 µg/L	0.23 µg/L
Triclosan	-	3 µg/L	4.8 µg/L	4.8 µg/L
Metals and trace elements in blood
Cadmium	0.04 µg/L	0.04 µg/L	0.080 µg/L	0.080 µg/L
Lead	0.02 µg/dL	0.1 µg/dL	0.16 µg/dL	0.16 µg/dL
Mercury (total)	0.1 µg/L	0.1 µg/L	0.42 µg/L	0.42 µg/L
Methylmercury	-	-	0.19 µg/L	0.19 µg/L
Metals and trace elements in urine
Fluoride	-	0.02 mg/L	0.012 mg/L	0.012 mg/L
Mercury (inorganic)	0.1 µg/L	-	0.16 µg/L	0.16 µg/L
Arsenic (speciated)
Arsenate	-	0.8 µg As/L^{Footnote a}	0.75 µg As/L	0.75 µg As/L
Arsenite	-	0.8 µg As/L^{Footnote a}	0.75 µg As/L	0.75 µg As/L
Arsenocholine	-	-	0.75 µg As/L	0.75 µg As/L
Arsenocholine and arsenobetaine	-	0.8 µg As/L^{Footnote a}	0.75 µg As/L	0.75 µg As/L
Dimethylarsinic acid	-	0.8 µg As/L^{Footnote a}	0.75 µg As/L	0.75 µg As/L
Monomethylarsonic acid	-	0.8 µg As/L^{Footnote a}	0.75 µg As/L	0.75 µg As/L
Nicotine metabolite
Cotinine	1 µg/L	1 µg/L	1.1 µg/L	1.1 µg/L
Organophosphate pesticide metabolites
Chlorpyrifos metabolite
3,5,6-Trichloro-2-pyridinol	-	-	NA^{Footnote b}	0.13 µg/L
Malathion metabolite
Malathion dicarboxylic acid	-	-	NA^{Footnote b}	0.19 µg/L
Parabens
Methyl paraben	-	-	NA^{Footnote b}	1.3 µg/L
Ethyl paraben	-	-	NA^{Footnote b}	0.90 µg/L
Propyl paraben	-	-	NA^{Footnote b}	0.30 µg/L
Butyl paraben	-	-	NA^{Footnote b}	0.30 µg/L
Polycyclic aromatic hydrocarbon metabolites
Benzo[a]pyrene metabolite
3-Hydroxybenzo[a]pyrene	-	0.002 µg/L	0.0029 µg/L	0.0029 µg/L
Chrysene metabolites
2-Hydroxychrysene	-	0.004 µg/L	0.0054 µg/L	0.0054 µg/L
3-Hydroxychrysene	-	0.003 µg/L	0.0026 µg/L	0.0026 µg/L
4-Hydroxychrysene	-	0.003 µg/L	0.0023 µg/L	0.0023 µg/L
6-Hydroxychrysene	-	0.006 µg/L	0.0025 µg/L	0.0025 µg/L
Fluoranthene metabolite
3-Hydroxyfluoranthene	-	0.008 µg/L	0.0080 µg/L	0.0080 µg/L
Fluorene metabolites
2-Hydroxyfluorene	-	0.003 µg/L	0.0064 µg/L	0.0064 µg/L
3-Hydroxyfluorene	-	0.001 µg/L	0.0020 µg/L	0.0020 µg/L
9-Hydroxyfluorene	-	0.003 µg/L	0.0045 µg/L	0.0045 µg/L
Naphthalene metabolites
1-Hydroxynaphthalene	-	0.1 µg/L	0.021 µg/L	0.021 µg/L
2-Hydroxynaphthalene	-	0.05 µg/L	0.031 µg/L	0.031 µg/L
Phenanthrene metabolites
1-Hydroxyphenanthrene	-	0.005 µg/L	0.0024 µg/L	0.0024 µg/L
2-Hydroxyphenanthrene	-	0.003 µg/L	0.0025 µg/L	0.0025 µg/L
3-Hydroxyphenanthrene	-	0.003 µg/L	0.0021 µg/L	0.0021 µg/L
4-Hydroxyphenanthrene	-	0.001 µg/L	0.0031 µg/L	0.0031 µg/L
9-Hydroxyphenanthrene	-	0.004 µg/L	0.0040 µg/L	0.0040 µg/L
Pyrene metabolite
1-Hydroxypyrene	-	0.002 µg/L	0.0029 µg/L	0.0029 µg/L
Volatile organic compounds
Benzene	-	-	0.0070 µg/L	0.0070 µg/L
Ethylbenzene	-	-	0.011 µg/L	0.011 µg/L
Styrene	-	-	0.012 µg/L	0.012 µg/L
Tetrachloroethylene (perchloroethylene)	-	-	0.020 µg/L	0.020 µg/L
Toluene	-	-	0.011 µg/L	0.011 µg/L
Trichloroethylene	-	-	0.027 µg/L	0.027 µg/L
Benzene metabolites
S-Phenylmercapturic acid	-	0.08 µg/L	0.080 µg/L	0.080 µg/L
trans,trans-Muconic acid	-	0.8 µg/L	0.61 µg/L	0.61 µg/L
Trihalomethanes
Bromodichloromethane	-	-	0.012 µg/L	0.012 µg/L
Dibromochloromethane	-	-	0.0070 µg/L	0.0070 µg/L
Tribromomethane (bromoform)	-	-	0.010 µg/L	0.010 µg/L
Trichloromethane (chloroform)	-	-	0.014 µg/L	0.014 µg/L
Xylenes
m-Xylene and p-xylene	-	-	0.023 µg/L	0.023 µg/L
o-Xylene	-	-	0.0090 µg/L	0.0090 µg/L
Adjustment factor
Creatinine	3 mg/dL	4 mg/dL	5.0 mg/dL	5.0 mg/dL
NA: Not available Footnote a In the Second Report on Human Biomonitoring of Environmental Chemicals in Canada, all speciated arsenic was reported as µg of arsenic species per litre (e.g. µg arsenate/L). For this reason, the values presented in this report may differ from those in the Second Report. Return to footnote a referrer Footnote b These chemicals were measured in cycle 3; however, the data are not yet available because ongoing quality assurance confirmation of the biospecimen analysis. Return to footnote b referrer

Appendix B: Conversion factors

Units of measurement are important. Results are reported here using standard units; however, units can be converted using the conversion factors presented below for comparison of data with other data sets.

Definition of Units
Unit	Abbreviation	Value
Litre	L
Decilitre	dL	10^-1 L
Millilitre	mL	10^-3 L
Microlitre	µL	10^-6 L
Gram	g
Milligram	mg	10^-3 g
Microgram	µg	10^-6 g
Nanogram	ng	10^-9 g
Picogram	pg	10^-12 g

Data can be converted from µg/L to µmol/L using the molecular weight (MW) of the chemical using the formula:

Y µmol/L = X µg/L ×conversion factor (CF), where the CF is equivalent to 1/MW.

Conversion Factors
Chemical	MW (g/mol)	CF (µg/L → µmol/L)
Acrylamide
Acrylamide haemoglobin adduct	-	NA
Glycidamide haemoglobin adduct	-	NA
Environmental phenols
Bisphenol A	228.29	0.00438
Triclosan	289.54	0.00345
Metals and trace elements
Cadmium	112.41	0.00896
Fluoride	19.00	0.05263
Lead	207.20	0.04826^{Footnote a}
Mercury	200.59	0.00499
Methylmercury	215.63	0.00464
Arsenic (speciated)
Arsenate	-	0.01335^{Footnote b}
Arsenite	-	0.01335^{Footnote b}
Arsenocholine	-	0.01335^{Footnote b}
Arsenocholine and arsenobetaine	-	0.01335^{Footnote b}
Dimethylarsinic acid	-	0.01335^{Footnote b}
Monomethylarsonic acid	-	0.01335^{Footnote b}
Nicotine metabolite
Cotinine	176.22	0.00567
Organophosphate pesticide metabolites
Chlorpyrifos metabolite
3,5,6-Trichloro-2-pyridinol	198.43	0.00504
Malathion metabolite
Malathion dicarboxylic acid	274.24	0.00365
Parabens
Methyl paraben	152.15	0.00657
Ethyl paraben	166.18	0.00602
Propyl paraben	180.20	0.00555
Butyl paraben	194.23	0.00515
Polycyclic aromatic hydrocarbon metabolites
Benzo[a]pyrene metabolite
3-Hydroxybenzo[a]pyrene	268.31	0.00373
Chrysene metabolites
2-Hydroxychrysene	244.29	0.00409
3-Hydroxychrysene	244.29	0.00409
4-Hydroxychrysene	244.29	0.00409
6-Hydroxychrysene	244.29	0.00409
Fluoranthene metabolite
3-Hydroxyfluoranthene	218.25	0.00458
Fluorene metabolites
2-Hydroxyfluorene	182.22	0.00549
3-Hydroxyfluorene	182.22	0.00549
9-Hydroxyfluorene	182.22	0.00549
Naphthalene metabolites
1-Hydroxynaphthalene	144.17	0.00694
2-Hydroxynaphthalene	144.17	0.00694
Phenanthrene metabolites
1-Hydroxyphenanthrene	194.23	0.00515
2-Hydroxyphenanthrene	194.23	0.00515
3-Hydroxyphenanthrene	194.23	0.00515
4-Hydroxyphenanthrene	194.23	0.00515
9-Hydroxyphenanthrene	194.23	0.00515
Pyrene metabolite
1-Hydroxypyrene	218.25	0.00458
Volatile organic compounds
Benzene	78.11	0.01280
Ethylbenzene	106.17	0.00942
Styrene	104.15	0.00960
Tetrachloroethylene (perchloroethylene)	165.83	0.00603
Toluene	92.14	0.01085
Trichloroethylene	131.39	0.00761
Benzene metabolites
trans,trans-Muconic acid	142.11	0.00704
S-Phenylmercapturic acid	239.29	0.00418
Trihalomethanes
Bromodichloromethane	163.83	0.00610
Dibromochloromethane	208.28	0.00480
Tribromomethane (bromoform)	252.73	0.00396
Trichloromethane (chloroform)	119.38	0.00838
Xylenes
m-Xylene and p-xylene	106.17	0.00942
o-Xylene	106.17	0.00942
Adjustment factor
Creatinine	113.12	88.4^{Footnote c}
NA: Not available Footnote a For converting Pb from µg/dL to µmol/L Return to footnote a referrer Footnote b For converting arsenic species from µg As/L to µmol As/L Return to footnote b referrer Footnote c For converting creatinine from mg/dL to µmol/L Return to footnote c referrer

Appendix C: Creatinine

Creatinine - Geometric means and selected percentiles of urine concentrations (mg/dL) for the Canadian population aged 6-79 years by age group, Canadian Health Measures Survey cycle 1 (2007-2009).
Cycle	n	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 6-79 years
1 (2007-2009)	5515	83 (78-89)	27 (23-30)	93 (86-99)	210 (200-220)	250 (240-260)
Males, 6-79 years
1 (2007-2009)	2663	100 (97-110)	36 (28-43)	110 (100-110)	230 (220-240)	270 (250-280)
Females, 6-79 years
1 (2007-2009)	2852	68 (62-74)	22 (18-25)	75 (66-84)	180 (160-190)	210 (200-230)
6-11 years
1 (2007-2009)	1042	66 (60-72)	24 (18-29)	74 (67-81)	140 (130-150)	170 (160-180)
12-19 years
1 (2007-2009)	992	120 (110-130)	39 (30-47)	130 (120-140)	250 (230-280)	300 (260-330)
20-39 years
1 (2007-2009)	1172	90 (81-100)	29 (22-36)	99 (91-110)	230 (210-240)	280 (250-300)
40-59 years
1 (2007-2009)	1221	78 (73-84)	24 (19-28)	86 (76-96)	210 (190-230)	240 (230-250)
60-79 years
1 (2007-2009)	1088	72 (68-75)	26 (22-31)	81 (77-85)	150 (140-160)	190 (170-220)

Creatinine - Geometric means and selected percentiles of urine concentrations (mg/dL) for the Canadian population aged 3-79 years by age group, Canadian Health Measures Survey cycle 2 (2009-2011).
Cycle	n	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 3-79 years
2 (2009-2011)	6299	100 (100-110)	35 (33-38)	110 (110-120)	240 (230-260)	280 (270-300)
Males, 3-79 years
2 (2009-2011)	3031	120 (120-130)	47 (42-53)	130 (120-150)	260 (240-280)	310 (280-340)
Females, 3-79 years
2 (2009-2011)	3268	89 (85-94)	30 (27-32)	100 (96-100)	200 (180-230)	250 (240-270)
3-5 years
2 (2009-2011)	572	59 (55-63)	26 (24-29)	61 (55-67)	110 (110-120)	140 (110-160)
6-11 years
2 (2009-2011)	1059	88 (83-94)	37 (33-42)	98 (94-100)	170 (160-170)	190 (170-210)
12-19 years
2 (2009-2011)	1042	130 (120-150)	52 (36-68)	150 (140-160)	270 (260-280)	300 (270-340)
20-39 years
2 (2009-2011)	1322	120 (110-130)	37 (25-48)	140 (130-160)	260 (250-280)	330 (270-380)
40-59 years
2 (2009-2011)	1223	100 (96-110)	33 (27-40)	110 (100-120)	240 (220-260)	280 (260-310)
60-79 years
2 (2009-2011)	1081	85 (80-89)	32 (26-37)	96 (90-100)	180 (170-200)	230 (210-260)

Creatinine - Geometric means and selected percentiles of urine concentrations (mg/dL) for the Canadian population aged 3-79 years by age group, Canadian Health Measures Survey cycle 3 (2012-2013).
Cycle	n	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 3-79 years
3 (2012-2013)	5704	97 (93-100)	33 (29-37)	100 (100-110)	240 (220-250)	280 (250-300)
Males, 3-79 years
3 (2012-2013)	2847	110 (110-120)	40 (35-46)	120 (110-130)	260 (230-280)	300 (260-340)
Females, 3-79 years
3 (2012-2013)	2857	83 (76-90)	26 (21-30)	93 (81-110)	210 (190-240)	250 (220-270)
3-5 years
3 (2012-2013)	521	51 (45-58)	19 (14-24)	58 (51-65)	110 (99-110)	120 (110-120)
6-11 years
3 (2012-2013)	1013	84 (77-92)	35 (28-42)	93 (82-100)	160 (150-180)	200 (170-230)
12-19 years
3 (2012-2013)	998	130 (120-150)	52 (37-66)	150 (140-160)	280 (260-300)	320 (290-360)
20-39 years
3 (2012-2013)	1048	110 (98-120)	36 (26-45)	110 (97-130)	270 (220-320)	330 (290-380)
40-59 years
3 (2012-2013)	1080	95 (86-110)	34 (24-44)	110 (98-110)	220 (200-250)	250 (230-280)
60-79 years
3 (2012-2013)	1044	84 (76-91)	26 (19-32)	96 (89-100)	190 (170-210)	230 (210-240)

Creatinine - Geometric means and selected percentiles of urine concentrations (mg/dL) for the Canadian population aged 3-79 years by age group, Canadian Health Measures Survey cycle 4 (2014-2015).
Cycle	n	GM (95% CI)	10^th (95% CI)	50^th (95% CI)	90^th (95% CI)	95^th (95% CI)
Total, 3-79 years
4 (2014-2015)	5603	110 (110-120)	40 (35-46)	110 (110-120)	250 (240-260)	290 (270-310)
Males, 3-79 years
4 (2014-2015)	2815	130 (120-140)	50 (40-60)	140 (120-150)	270 (250-290)	320 (310-330)
Females, 3-79 years
4 (2014-2015)	2788	98 (94-100)	35 (30-39)	100 (98-100)	230 (210-240)	260 (250-270)
3-5 years
4 (2014-2015)	513	58 (51-65)	22 (15-29)	66 (58-73)	110 (99-120)	130 (120-150)
6-11 years
4 (2014-2015)	1008	90 (84-98)	35 (24-45)	99 (94-100)	170 (150-190)	210 (170-250)
12-19 years
4 (2014-2015)	991	140 (130-150)	54 (46-61)	150 (140-170)	280 (270-300)	350 (320-370)
20-39 years
4 (2014-2015)	1059	130 (120-140)	41 (36-47)	140 (130-160)	290 (260-320)	350 (320-390)
40-59 years
4 (2014-2015)	1037	110 (100-120)	41 (29-54)	110 (110-120)	240 (220-260)	270 (260-280)
60-79 years
4 (2014-2015)	995	100 (97-110)	37 (32-42)	100 (100-110)	200 (180-220)	240 (210-270)

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Footnotes

Footnote a

If >40% of samples were below the LOD, the percentile distribution is reported but means were not calculated.

Return to footnote a referrer

Footnote b

Data not available as participants under the age of 6 years were not included in cycle 1 (2007-2009).

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Footnote c

For each individual within a cycle, the sum of arsenate, arsenite, dimethylarsinic acid, and monomethylarsonic acid is calculated. If the value of a species is less than the limit of detection (LOD), then the imputed value calculated as LOD divided by 2 is used. If all four arsenic species are reported as less than the LOD, then the sum will be the sum of the four imputed values.

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Footnote E

Use data with caution.

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Footnote F

Data is too unreliable to be published.

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Footnote X

Suppressed to meet the confidentiality requirements of the Statistics Act.

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Date modified:: 2017-08-23