Indoor Air Reference Levels for Chronic Exposure to Volatile Organic Compounds

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Organization: Health Canada
Date published: 2018-02-05
Water and Air Quality Bureau
Healthy Environments and Consumer Safety Branch
Health Canada is the federal department responsible for helping the people of Canada maintain and improve their health. We assess the safety of drugs and many consumer products, help improve the safety of food, and provide information to Canadians to help them make healthy decisions. We provide health services to First Nations people and to Inuit communities. We work with the provinces to ensure our health care system serves the needs of Canadians.
Également disponible en français sous le titre : Niveaux de référence dans l’air intérieur liés à l’exposition chronique aux composés organiques volatils : document de synthèse
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Publication date: October 2017
This publication may be reproduced for personal or internal use only without permission provided the source is fully acknowledged. However, multiple copy reproduction of this publication in whole or in part for purposes of resale or redistribution requires the prior written permission from the Minister of Public Works and Government Services Canada, Ottawa, Ontario K1A 0S5 or copyright.droitdauteur@pwgsc.gc.ca.
Cat.: H144-48/2017E-PDF
ISBN: 978-0-660-23532-5
Table of contents
- List of acronyms
- 1.0 Introduction
- 2.0 Considerations in the determination of Indoor Air Reference Levels
- 3.0 Application of Indoor Air Reference Levels
- 4.0 Uncertainties and assumptions in hazard and exposure assessments
- 5.0 Indoor Air Reference Levels
- 6.0 Tables of TRVs for individual VOCs
- 7.0 Tables of TRVs for individual VOCs (no IARLs recommended)
- 8.0 References
List of tables
List of acronyms
- AEL
- Adverse Effect Level
- ATSDR
- Agency for Toxic Substances and Disease Registry
- BMC
- benchmark concentration
- BMCL
- benchmark concentration (lower limit of a one-sided 95% confidence interval on the BMC)
- BMD
- benchmark dose
- BMDL
- benchmark dose (lower limit of a one-sided 95% confidence interval on the BMD)
- CalEPA
- California Environmental Protection Agency
- COHb
- carboxyhemoglobin
- DAF
- dosimetric adjustment factor
- HEC
- human equivalent concentration
- IARL
- indoor air reference level
- LEC
- lowest effective concentration
- LOAEL
- lowest observed adverse effect level
- NOAEL
- no observed adverse effect level
- PBPK
- physiologically based pharmacokinetic
- PoD
- point of departure
- RfC
- reference concentration
- RGDR
- regional gas dose ratio
- RIAQG
- Residential Indoor Air Quality Guideline
- RIVM
- National Institute for Public Health and the Environment
- TC
- tolerable concentration
- TC01, TC05
- tumorigenic concentration (concentration of a contaminant in air generally associated with a 1% or 5% increase in incidence or mortality due to tumours, respectively)
- TRV
- toxicological reference value
- UF
- uncertainty factor
- UFA
- uncertainty factor for interspecies variability
- UFDB
- uncertainty factor for database deficiency
- UFH
- uncertainty factor for intraspecies variability
- UFL
- uncertainty factor for use of a LOAEL or effect level extrapolation factor
- UFs
- uncertainty factor for study duration
- US EPA
- United States Environmental Protection Agency
- VCCEP
- Voluntary Children’s Chemical Evaluation Program
- VOC
- volatile organic compound
- WHO
- World Health Organization
1.0 Introduction
Volatile organic compounds (VOCs) are a diverse group of chemicals characterized by a high vapour pressure, as they are emitted in the form of a gas from solids or liquids at ordinary room temperatures.Footnote 1 They are ubiquitous since they are found in both ambient and indoor air.
Known or suspected human health effects of VOCs vary considerably from one compound to another and with respect to the level of exposure. Levels of different VOCs present in the home depend on indoor sources (e.g., smoking, cooking, combustion appliances, building materials, furniture, and a wide range of consumer products) as well as infiltration of VOCs from outdoors (Health Canada 2017) or from an attached garage (Mallach et al. 2017). Strength of emissions, changes in emissions over time, adsorption and desorption processes, secondary reactions with other chemicals, and amount of ventilation in different rooms and in the house as a whole, all influence the levels of VOCs that may be measured at any given time.
For a given VOC, the indoor air reference level (IARL) for chronic exposure is an estimate of a concentration limit for continuous long-term inhalation exposures (up to a lifetime) below which adverse health effects are not expected to occur. In the case of carcinogenic substances, the IARL is an estimate of the continuous lifetime exposure associated with a negligible cancer risk.Footnote 2 The IARL applies to the general population including vulnerable subgroups.
Indoor air reference levels are intended to supplement Health Canada’s Residential Indoor Air Quality Guidelines (RIAQGs), which are based on comprehensive reviews of the literature, are externally peer-reviewed, and are submitted for public comment. In developing IARLs, the Health Canada review is limited to hazard assessments from internationally recognized health and environmental organizationsFootnote 3 and the key studies identified in these assessments.
This overview document provides a summary of IARLs for chronic exposure to VOCs that are current as of December 2016. This document, along with the derived IARLs, will be updated periodically to reflect changes in the hazard assessments that form the basis of these values. Details on the methodology for selecting VOCs for evaluation and deriving IARLs can be found in the companion document Derivation of Health Canada Indoor Air Reference Levels: Methodology for Volatile Organic Compounds (Health Canada 2013). The methodology describes criteria for evaluating hazard assessments on the basis of the strength of the underlying science as well as consistency with Health Canada policies and practice.
2.0 Considerations in the determination of indoor air reference levels
Authoritative agencies and organizations follow similar procedures for conducting hazard assessments for cancer and non-cancer endpoints. Generally, hazard assessments lead to the derivation of toxicological reference values (TRVs). The TRV nomenclature varies among the different organizations and includes chronic reference exposure level, reference concentration (RfC), tolerable concentration (TC), and minimal risk level. These all provide a quantitative value below which adverse non-cancer health effects are not expected to be observed for durations of up to a lifetime exposure, including consideration of vulnerable and susceptible subpopulations. For non-threshold carcinogenic effects, the TRVs are often referred to as cancer potency factors, slope factors or inhalation unit risks. For these TRVs, it is necessary to define the level of potential excess lifetime cancer risk that would be considered negligible or acceptable. For the purpose of IARLs, a risk level of 1 in 100 000 is retained.
For some VOCs, both cancer and non-cancer TRVs have been derived. Assessments for cancer and non-cancer health endpoints are considered independently, and the most appropriate TRV for each effect is identified. The IARL is typically based on the most conservative value of the selected cancer and non-cancer TRVs, but might vary depending on the mode of action of carcinogenesis.
No IARL was determined in cases where the available assessments were considered inadequate. The specific reasons for such a conclusion are included in the rationale of the individual substance report.
3.0 Application of indoor air reference levels
The primary use of IARLs is to evaluate the health impacts of indoor VOC emissions from building materials and consumer products. On the basis of the measured emission factors and assumptions about typical product use and building characteristics, indoor air concentrations of different VOCs can be estimated. The associated potential health risks may then be evaluated by comparing estimated concentrations with IARLs.
In addition to working to promote the development of Canadian standards, Health Canada may collaborate with other international organizations in developing new health-based emission standards or in promoting the use of an existing standard. The IARLs provide benchmarks for Health Canada to evaluate VOC product emission standards produced internationally and endorse such standards when appropriate.
In some cases, a VOC may be produced primarily by sources other than building materials or consumer products (e.g., certain VOCs produced by fuel combustion). In these cases, IARLs may also be used to identify VOCs in the indoor environment of greatest potential concern to health and in support of the development of appropriate risk management actions.
Derivation of an IARL is also the first step in determining if a full assessment leading to an RIAQG is required and if so, the level of priority for such an assessment. The framework for this prioritization process is included as well in the aforementioned Health Canada document published in 2013. If an RIAQG is subsequently developed, this guideline value would supersede the IARL in risk management and communication actions.
4.0 Uncertainties and assumptions in hazard and exposure assessments
All hazard assessments must consider the uncertainties in the underlying toxicological and epidemiological data. Assumptions with respect to intraspecies variability, interspecies extrapolation, and/or extrapolation from high to low levels of exposure as well as adjustments related to exposure patterns and duration of toxicological studies are inherent in the hazard assessment process. The completeness of the scientific literature with respect to the range of potential health effects on different subpopulations also varies considerably from one compound to another. In deriving a TRV, these uncertainties are addressed through the use of uncertainty factors applied in a precautionary manner. Variability and uncertainty can also be addressed using chemical-specific data (e.g., with the application of physiologically-based pharmacokinetic models or chemical-specific adjustment factors). This approach allows health organizations to determine a level of exposure that would not be expected to result in adverse effects, based on the information available at the time of the assessment.
There are also major uncertainties in estimating indoor air concentrations over long periods of time in Canadian homes. In particular, if the indoor air concentration is modelled on the basis of VOC emissions from products, as measured in chamber tests, the estimated long-term indoor air concentration may be quite different from the actual measured concentration over time. Factors influencing this estimate include the number and type of source materials, patterns of use, age of the material, and rate of decay of the emissions over time as well as home environmental conditions (e.g., temperature, humidity, ventilation rate, presence of reactive compounds). If the indoor air concentration is based on measured concentrations in Canadian homes, the type, location, and number of homes as well as the demographics of the study participants may limit the representativeness of the measured concentrations.
Given these uncertainties, any comparison of an estimated indoor air concentration with an IARL should be interpreted as providing an indication of potential risk and not a measure of actual risk. The level of uncertainty in risk estimates may be reduced through additional health or exposure data. For example, population-based epidemiological studies may provide more information for evaluating health effects at low concentrations typically encountered in the home. Furthermore, emission testing under more realistic conditions, or modelling with inputs that are more specific to the material or environment under consideration, may also reduce the overall uncertainty in risk estimates.
5.0 Indoor air reference levels
The methodology for selecting IARLs has been previously presented (Health Canada 2013). Table 1 summarizes the IARLs identified for selected VOCs as well as the critical effect on which the IARL is based and the source of the underlying TRV. Summary tables of the TRVs are presented in Section 6.
The derivation of each IARL is documented in a separate report. These individual substance reports are available upon request (air@hc-sc.gc.ca).
Indoor air reference levels were not reported for acetaldehyde as Health Canada is currently undertaking a full risk assessment. Should new data become available for the remaining VOCs, a reevaluation of the IARLs will be completed on a cyclical basis.
VOCTable 1 - Footnote 1 | IARL (µg/m3) |
Critical Effect | Reference | |
---|---|---|---|---|
Cancer | Non-Cancer | |||
1,3-Butadiene |
1.7 |
leukemia |
- | EC/HC (2000a) |
1,4-Dichlorobenzene |
60 |
- | nasal lesions |
ATSDR (2006) |
2-Butoxyethanol |
11 000 |
- | hematological effects |
EC/HC (2002) |
2-Ethoxyethanol |
70 |
- | testicular degeneration and hematological changes |
CalEPA (2000) |
3-Chloropropene |
1 |
- | peripheral nerve damage |
US EPA (1991) |
AcetaldehydeTable 1 - Footnote 2 |
|
- | - | - |
Acetone |
70 000 |
- | developmental effects |
VCCEP (2003) |
Acrolein |
0.35 |
- | respiratory epithelial lesions |
CalEPA (2008) |
Aniline |
1 |
- | effects on spleen |
US EPA (1990a) |
Carbon tetrachloride |
1.7 |
adrenal gland tumours |
- | US EPA (2010) |
Chloroform |
300 |
- | kidney and liver toxicity |
CalEPA (2000) |
Cyclohexane |
6000 |
- | reduced pup weight |
US EPA (2003a) |
Dichloromethane |
600 |
- | effects on liver |
US EPA (2011) |
Epichlorohydrin |
1 |
- | histological changes in the nose |
US EPA (1994) |
Ethylbenzene |
2000 |
- | effects on, pituitary gland and liver |
CalEPA (2000) |
Ethylene oxide |
0.002 |
lymphoid and breast cancer |
- | US EPA (2016) |
Isopropyl alcohol |
7000 |
- | kidney lesions |
CalEPA (2000) |
IsopropylbenzeneTable 1 - Footnote 3 |
400 |
- | effects on kidney |
US EPA (1997) |
Methyl ethyl ketone |
5000 |
- | developmental effects |
US EPA (2003b) |
Methyl isobutyl ketoneTable 1 - Footnote 3 |
3000 |
- | developmental effects |
US EPA (2003c) |
Propionaldehyde |
8 |
- | olfactory epithelium atrophy |
US EPA (2008) |
Propylene oxide |
2.7 |
nasal cavity tumours |
- | US EPA (1990b) |
Styrene |
850 |
- | neurotoxicity |
ATSDR (2010) |
Tetrachloroethylene |
40 |
- | neurotoxicity, visual impairment, and neurobehavioural effects |
US EPA (2012), ATSDR (2014) |
Toluene diisocyanate |
0.008 |
- | decreased lung function |
CalEPA (2016) |
Xylenes, mixture |
100 |
- | increased sensitivity to pain |
US EPA (2003d) |
6.0 Table of TRVS for individual VOCS
OrganizationTable 2 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | |||
---|---|---|---|---|---|
CalEPA | Health CanadaTable 2 - Footnote 2 | US EPA | CalEPA | US EPA | |
Year of publication |
2000 |
2002 |
2002 |
||
Species |
Mice |
Humans |
Humans |
Mice |
Mice |
Endpoint |
Lung tumours |
Leukemia |
Leukemia |
Ovarian atrophy |
Ovarian atrophy |
Unit risk (µg/m3)-1 |
1.7 x 10-4 |
5.9 x 10-6 |
3 x 10-5 |
- | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
17 |
1.7 |
0.3 |
- | - |
Point of departure |
- | - | - | BMCL05 HEC = 0.664 mg/m3 |
BMCL10 HEC = 2 mg/m3 |
Uncertainty factorsTable 2 - Footnote 4 |
- | - | - | 300 |
1000 |
Concentration (µg/m3) |
- | - | - | 2.2 |
2 |
Critical studyTable 2 - Footnote 5 |
1 |
2 |
2 |
3 |
3 |
Comments |
- | TC01 = 1.7 mg/m3 Unit risk = (0.01)/TC01 |
LEC01 = 300 µg/m3 with adjustments from Health Canada and further adjustment for cancer incidence not mortality. |
BMCL05 HEC: Benchmark concentration adjusted for continuous exposure and dosimetric differences between rats and humans (using PBPK model data): |
US EPA expressed medium confidence in the study selected, but low confidence in the dataset and resulting reference concentration. [Suggested by application of UFL to a BMCL.] |
OrganizationTable 3 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | ||||
---|---|---|---|---|---|---|
CalEPA | ATSDRTable 3 - Footnote 2 | CalEPA | Health Canada | RIVM | US EPA | |
Year of publication |
2006 |
1993c; 1996 |
2001 |
1994 |
||
Species |
Mice |
Rats |
Rats |
Rats |
Rats |
Rats |
Endpoint |
Liver tumours |
Nasal lesions |
Reduced body weight and food consumption; tremors; nasal and ocular discharge; increased liver and kidney weights |
Increased liver and kidney weights; increased urinary protein/coproporphyrin |
Increased liver and kidney weights; increased urinary protein/coproporphyrin |
Increased liver weight |
Unit risk (µg/m3)-1 |
1.1 x 10-5 |
- | - | - | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
0.9 |
- | - | - | - | - |
Point of departure |
- | LOAEL = 450 mg/m3 |
LOAEL = 900 mg/m3 |
LOAEL = 3000 mg/m3 |
LOAEL = 3000 mg/m3 |
LOAEL = 900 mg/m3 |
Uncertainty factorsTable 3 - Footnote 4 |
- | 30 |
100 |
500 |
100 |
100 |
Concentration (µg/m3) |
- | 60 |
800 |
95 |
670 |
800 |
Critical studyTable 3 - Footnote 5 |
1 |
2, 3 |
4 |
5 |
6 |
4 |
Comments |
- | BMCL10 HE = NOAEL x 5/7 days x 6/24 hours x 0.16 (RGDR) |
NOAELHEC = NOAEL x 7/7 days x 6/24 hours x 1.0 (RGDR) |
NOAELHEC = NOAEL x 5/7 days x 6/24 hours x 0.71 (breathing rate adjustment) |
NOAELADJ = NOAEL x 5/7 days x 5/24 hours x 0.71 (breathing rate adjustment). |
NOAELHEC = NOAEL x 7/7 days x 6/24 hours |
OrganizationTable 4 - Footnote 1 | NON-NEOPLASTIC | ||
---|---|---|---|
ATSDR | Health CanadaTable 4 - Footnote 2 | US EPA | |
Year of publication |
1998 |
2002 |
2010 |
Species |
Humans |
Rats |
Rats |
Endpoint |
Hematological effects |
Hematological effects |
Hemosiderin deposition |
Point of departure |
NOAEL = 2.9 mg/m3 |
BMC05 = 5.3 mg/m3 |
BMCL10,HEC = 16 mg/m3 |
Uncertainty factorsTable 4 - Footnote 3 |
3 |
0.5 |
10 |
Concentration (µg/m3) |
970 |
11 000 |
1600 |
Critical studyTable 4 - Footnote 4 |
1 |
2 |
2 |
Comments |
The small significant effects on hematological parameters reported in humans were within the range of normal clinical values (hence the concentration was designated a NOAEL). |
UFA includes adjustment factors of 0.5 (toxicokinetics) and 0.1 (toxicodynamics) to account for lower sensitivity of humans compared to rats. |
The BMCL10,HEC was back-calculated from the BMCL10 for 2-butoxyacetic acid (area under the curve in blood = 133 µmol-hour/L) using a PBPK model. US EPA has high confidence in the study, and a medium-to-high confidence in the RfC and database. |
Organization | NON-NEOPLASTIC | ||
---|---|---|---|
CalEPATable 5 - Footnote 1 | US EPA | WHO | |
Year of publication |
1991 |
2010 |
|
Species |
Rabbits |
Rabbits |
Rats |
Endpoint |
Testicular degeneration and hematological changes |
Testicular degeneration and hematological changes |
Developmental toxicity |
Unit risk (µg/m3)-1 |
- | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
- | - | - |
Point of departure |
NOAEL = 380 mg/m3 |
NOAEL = 380 mg/m3 |
NOAEL = 40 mg/m3 |
Uncertainty factorsTable 5 - Footnote 3 |
1000 |
300 |
100 |
Concentration (µg/m3) |
70 |
200 |
100 |
Critical studyTable 5 - Footnote 4 |
1 |
1 |
2, 3 |
Comments |
LOAEL = 1485 mg/m3 NOAELADJ = NOAEL x 6 hours/24 hours x 5 days/7 days NOAELHEC = NOAELADJ x 1 (RGDR) |
LOAEL = 1485 mg/m3 NOAELADJ = NOAEL x 6 hours/24 hours x 5 days/7 days NOAELHEC = NOAELADJ x 1 (RGDR) US EPA has medium confidence in the study, database and RfC. |
NOAELADJ = NOAEL x 6 hours/24 hours |
Organization | NEOPLASTIC | NON-NEOPLASTIC |
---|---|---|
CalEPA | US EPATable 6 - Footnote 1 | |
Year of publication |
1991 |
|
Species |
Mice |
Rabbits and rats |
Endpoint |
Squamous cell papillomas and carcinomas of the forestomach |
Peripheral nerve damage |
Unit risk (µg/m3)-1 |
6.0 x 10‑6 |
- |
Concentration at 1 x 10-5 risk level (µg/m3) |
1.67 |
- |
Point of departure |
- | NOAEL = 17 mg/m3 |
Uncertainty factorsTable 6 - Footnote 3 |
- | 3000 |
Concentration (µg/m3) |
- | 1 |
Critical studyTable 6 - Footnote 4 |
1 |
2 |
Comments |
Inhalation unit risk derived from an oral cancer potency factor in female mice exposed by gavage |
NOAELADJ = NOAEL x 6 hours/24 hours x 6 days/7 days NOAELHEC = NOAELADJ x 1 (RGDR) US EPA has low confidence in the study, database and RfC. |
OrganizationTable 7 - Footnote 1 | NON-NEOPLASTIC | |
---|---|---|
ATSDR | VCCEPTable 7 - Footnote 2 | |
Year of publication |
1994 |
2003 |
Species |
Humans |
Rats |
Endpoint |
Neurological effects |
Developmental effects |
Point of departure |
LOAEL = 3000 mg/m3 |
NOAEL = 5300 mg/m3 |
Uncertainty factorsTable 7 - Footnote 3 |
100 |
30 |
Concentration (µg/m3) |
31 000 |
70 000 |
Critical studyTable 7 - Footnote 4 |
1 |
2 |
Comments |
- | NOAELHEC calculated using PBPK modelling |
OrganizationTable 8 - Footnote 1 | NON-NEOPLASTIC | ||
---|---|---|---|
CalEPATable 8 - Footnote 2 | Health Canada | US EPA | |
Year of publication |
2000 |
2003 |
|
Species |
Rats |
Rats |
Rats |
Endpoint |
Respiratory epithelial lesions |
Respiratory epithelial lesions |
Respiratory epithelial lesions |
Point of departure |
LOAEL = 1400 µg/m3 |
BMC05 = 141 µg/m3 |
LOAEL = 900 µg/m3 |
Uncertainty factorsTable 8 - Footnote 4 |
200 |
100 |
1000 |
Concentration (µg/m3) |
0.35 |
0.4 |
0.02 |
Critical studyTable 8 - Footnote 5 |
1 |
2 |
3 |
Comments |
NOAELHEC = NOAEL x 5/7 days x 6/24 hours x 0.85 (DAF) |
BMC05 ADJ = BMC05 x 6/24 hours |
NOAELHEC = NOAEL x 5/7 days x 6/24 hours x 0.14 (RGDR) |
Organization | NEOPLASTIC | NON-NEOPLASTIC |
---|---|---|
CalEPA | US EPATable 9 - Footnote 1 | |
Year of publication |
1990 |
|
Species |
Rats |
Rats |
Endpoint |
Spleen tumours |
Effects on spleen |
Unit risk (µg/m3)-1 |
1.6 x 10‑6 |
- |
Concentration at 1 x 10-5 risk level (µg/m3) |
6.25 |
- |
Point of departure |
- | NOAEL = 19 mg/m3 |
Uncertainty factorsTable 9 - Footnote 3 |
- | 3000 |
Concentration (µg/m3) |
- | 1 |
Critical studyTable 9 - Footnote 4 |
1 |
2, 3 |
Comments |
Based on a US EPA oral slope factor. US EPA (1994) did not derive an inhalation unit risk. |
NOAELADJ = NOAEL x 6 hours/24 hours x 5 days/7 days NOAELHEC = NOAELADJ x 1 (RGDR) US EPA has low confidence in the study, database and RfC. |
NEOPLASTIC | NON-NEOPLASTIC | ||||||
---|---|---|---|---|---|---|---|
OrganizationTable 10 - Footnote 1 | CalEPA | US EPATable 10 - Footnote 2 | ATSDR | CalEPA | RIVM | US EPA | WHO |
Year of publication |
2010 |
2005 |
2001 |
2010 |
1999 |
||
Species |
Mice |
Mice |
Rats |
Guinea pigs |
Rats |
Rats |
Rats |
Endpoint |
Hepatomas |
Adrenal gland tumours |
Liver toxicity |
Liver toxicity |
Liver toxicity |
Liver toxicity |
Liver and kidney toxicity |
Unit risk (µg/m3)-1 |
4.2 x 10-5 |
6 x 10-6 |
- | - | - | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
0.24 |
1.7 |
- | - | - | - | - |
Point of departure |
- | - | NOAEL = 32 mg/m3 |
LOAEL = 32 mg/m3 |
NOAEL = 32 mg/m3 |
BMCL10 HEC = 14.3 mg/m3 |
(1) NOAEL = 6.1 mg/m3 |
Uncertainty factorsTable 10 - Footnote 4 |
- | - | 30 |
300 |
100 |
100 |
(1) 1000 |
Concentration (µg/m3) |
- | - | 190 |
40 |
60 |
100 |
(1) 6.1 |
Critical studyTable 10 - Footnote 5 |
1 |
2, 3 |
3 |
4 |
5 |
2, 3 |
(1) 6 |
Comments |
Linear multistage procedure Single treated dose |
BMD modelling with PBPK to get LEC10 from which unit risk was calculated. |
NOAELHEC = NOAEL 5/7 days x 6/24 hr x 1 (RGDR) |
LOAELHEC = LOAEL 5/7 days x 7/24 hr x 1.7 (RGDR) |
NOAELHEC = NOAEL 5/7 days x 7/24 hr |
BMD with PBPK to estimate BMDL10, converted to human equivalent. |
Three TCs were derived based on three different studies. |
OrganizationTable 11 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | ||||
---|---|---|---|---|---|---|
CalEPA | Health Canada | US EPA | ATSDR | CalEPATable 11 - Footnote 2 | RIVM | |
Year of publication |
2001 |
2001 |
1997 |
2001 |
||
Species |
Rats |
Rats |
Mice |
Humans |
Rats |
Rats |
Endpoint |
Kidney tumours |
Kidney tumours |
Hepatocellular carcinoma |
Liver toxicity |
Kidney and liver toxicity |
None |
Unit risk (µg/m3)-1 |
5.3 x 10-6 |
- | 2.3 x 10-5 |
- | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
1.9 |
- | 0.4 |
- | - | - |
Point of departure |
- | - | - | LOAEL = 10 mg/m3 |
LOAEL = 120 mg/m3 |
NOAEL = 110 mg/m3 |
Uncertainty factorsTable 11 - Footnote 4 |
- | - | - | 100 |
300 |
1000 |
Concentration (µg/m3) |
- | 147 000 |
- | 100 |
300 |
100 |
Critical studyTable 11 - Footnote 5 |
1, 2, 3, 4 |
1 |
2 |
5 |
6 |
6 |
Comments |
Linear multistage procedure with PBPK |
PBPK used to determine 3.9 mg/L per hour, the rate of metabolism associated with a 5% increase in tumour risk (TC05). |
Linearized multistage procedure, extra risk |
- | LOAELHEC = LOAEL x 5/7 days x 7/24 hours x 3 (RGDR) |
UFS for 4 hour/day, 5 days/week, 6-month exposure. |
Organization | NON-NEOPLASTIC |
---|---|
US EPATable 12 - Footnote 1 | |
Year of publication |
2003 |
Species |
Rats |
Endpoint |
Reduced pup weight (F1 and F2 generations) |
Point of departure |
NOAEL = 6886 mg/m3 |
Uncertainty factorsTable 12 - Footnote 3 |
300 |
Concentration (µg/m3) |
6000 |
Critical studyTable 12 - Footnote 4 |
1, 2 |
Comments |
NOAELADJ = NOAEL x 6/24 hours x 1 (RGDR) |
OrganizationTable 13 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | |||||
---|---|---|---|---|---|---|---|
CalEPA | Health Canada | US EPA | ATSDR | CalEPA | RIVM | US EPATable 13 - Footnote 2 | |
Year of publication |
1993 |
2011 |
2000 |
2001 |
2011 |
||
Species |
Mice |
Mice |
Mice |
Rats |
Humans |
Humans |
Rats |
Endpoint |
Lung tumours |
Lung tumours |
Lung and liver tumours |
Effects on liver |
Increased carboxyhemoglobin |
Increased carboxyhemoglobin |
Effects on liver |
Unit risk (µg/m3)-1 |
1.0 x 10-6 |
2.3 x 10-8 |
1.0 x 10-8 |
- | - | - | |
Concentration at 1 x 10-5 risk level (µg/m3) |
10 |
435 |
1000 |
- | - | - | |
Point of departure |
- | - | - | NOAEL = 170 mg/m3 |
LOAEL = 139 000 mg/m3 |
LOAEL = 90 mg/m3 |
BMDL10 = 532 mg dichloromethane metabolized via CYP pathway/L liver tissue/day |
Uncertainty factorsTable 13 - Footnote 4 |
- | - | - | 30 |
100 |
0 |
30 |
Concentration (µg/m3) |
- | - | - | 1000 |
400 |
3000 |
600 |
Critical studyTable 13 - Footnote 5 |
1, 2 |
1, 2 |
1, 2 |
3 |
4 |
4 |
3 |
Comments |
- | Based on the lowest PBPK modified TD0.05 value. |
Application of age-dependent adjustment factors results in a 70-year risk of 1.7 x 10-8. |
NOAELADJ = NOAEL 5/7 days x 6/24 hours |
LOAELADJ = LOAEL x 5/7 days x [(10 m3/d)/(20 m3/d)] |
LOAELADJ = LOAEL x 5/7 days x 7.5/24 hours x (0.1/1). The last factor was to adjust for an unacceptable 0.1% increase in COHb, relative to the observed 1% COHb increase. |
HEC1% determined by PBPK modelling of calculated BMDL10 value. |
Organization | NEOPLASTIC | NON-NEOPLASTIC | ||
---|---|---|---|---|
CalEPA | US EPA | CalEPA | US EPATable 14 - Footnote 1 | |
Year of publication |
1988 |
2001 |
1994 |
|
Species |
Rats |
Rats |
Rats and mice |
Rats and mice |
Endpoint |
Papillomas and carcinomas of the forestomach |
Nasal cavity tumours |
Histological changes in the nose |
Histological changes in the nose |
Unit risk (µg/m3)-1 |
2.3 x 10-5 |
1.2 x 10-6 |
- | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
0.43 |
8 |
- | - |
Point of departure |
- | - | NOAEL = 19 mg/m3 |
NOAEL = 19 mg/m3 |
Uncertainty factorsTable 14 - Footnote 3 |
- | - | 100 |
300 |
Concentration (µg/m3) |
- | - | 3 |
1 |
Critical studyTable 14 - Footnote 4 |
1 |
2 |
3 |
3 |
Comments |
Inhalation unit risk derived from oral cancer potency factor in male rats exposed via drinking water. |
- | NOAELADJ = NOAEL x 6 hours/24 hours x 5 days/7 days NOAELHEC = NOAELADJ x 0.14 m3/day / 20 m3/day x 200 cm2/15 cm2 (based on rat data) |
NOAELADJ = NOAEL x 6 hours/24 hours x 5 days/7 days NOAELHEC= NOAELADJ x 0.14 m3/day / 20 m3/day x 177 cm2/11.6 cm2 (based on rat data) US EPA has medium confidence in the RfC, in the study and in the database. |
OrganizationTable 15 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | ||||||
---|---|---|---|---|---|---|---|---|
CalEPA | VCCEP | ATSDR | CalEPATable 15 - Footnote 2 | RIVM | US EPA | VCCEP | WHO | |
Year of publication |
2007 |
2010 |
2001 |
1991 |
2007 |
1996 |
||
Species |
Rats |
Mice |
Rats |
Rats and mice |
Rats and mice |
Rabbits |
Rats |
Rats and mice |
Endpoint |
Kidney tumours |
Lung tumours |
Effects on kidney |
Effects on pituitary gland and liver (mice) |
Effects on liver and kidney |
Developmental effects |
Auditory effects |
Effects on liver and kidney |
Unit risk (µg/m3)-1 |
2.5 x 10-6 |
- | - | - | - | - | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
4 |
- | - | - | - | - | - | - |
Point of departure |
- | 40 500 mg metabolised in lung/kg lung/wk |
LOAEL = 330 mg/m3 |
LOAEL = 1100 mg/m3 |
NOAEL = 430 mg/m3 |
LOAEL = 4340 mg/m3 |
LOEL = 860 mg/m3 |
NOEL = 2150 mg/m3 |
Uncertainty factorsTable 15 - Footnote 6 |
- | 300 |
300 |
30 |
100 |
300 |
100 |
100 |
Concentration (µg/m3) |
- | 2100 |
260 |
2000 |
770 |
1000 |
1300 |
22 000 |
Critical studyTable 15 - Footnote 7 |
1 |
1 |
1 |
1, 2 |
3 |
4, 5 |
6 |
3 |
Comments |
More recent evidence suggests ethylbenzene may be a threshold carcinogen. |
- | More recent data suggest effects on kidney, particularly chronic progressive nephropathy (common in aging rats), are unlikely to be relevant to humans. |
NOAELADJ = NOAEL x 5/7 days x 6/24 hours |
NOAELADJ = |
US EPA has low confidence in this derivation; published prior to NTP (1999). |
Sub-chronic study supportive of chronic effects |
Stated NOAEL would be higher than 4300 mg/m3 because organ weight increases were not accompanied by cellular changes. |
OrganizationTable 16 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | |||
---|---|---|---|---|---|
CalEPA | Health Canada | US EPATable 16 - Footnote 2 | CalEPA | ||
Year of publication |
2001 |
2016 |
|||
Species |
Rats |
Rats |
Humans |
Rats |
|
Endpoint |
Mononuclear leukemia |
Mononuclear leukemia |
Lymphoid and breast cancer |
Neurological effects |
|
Unit risk (µg/m3)-1 |
8.8 x 10-5 |
2.3 x 10-5 |
5.0 x 10-3 |
||
Concentration at 1 x 10-5 risk level (µg/m3) |
0.11 |
0.43 |
0.002 |
||
Point of departure |
- | - | - | NOAEL = 18 mg/m3 |
|
Uncertainty factorsTable 16 - Footnote 4 |
- | - | - | 100 |
|
Concentration (µg/m3) |
- | - | - | 30 |
|
Critical studyTable 16 - Footnote 5 |
1 |
2 |
3 |
2 |
|
Comments |
Based on a 1985 US EPA analysis that considered human equivalent dose |
Unit risk of 2.3 x 10-5 (µg/m3)-1 estimated from TC05 value of 2.2 mg/m3 |
Adult-based value was 3.0 x 10‑3 per µg/m3, to which age-dependent adjustment factors were applied to provide the lifetime exposure value presented above. |
NOAELADJ = PoD x 5/7 days x 6/24 hours |
|
Organization | NON-NEOPLASTIC |
---|---|
CalEPATable 17 - Footnote 1 | |
Year of publication |
|
Species |
Rats and mice |
Endpoint |
Kidney lesions |
Point of departure |
NOAEL = 1200 mg/m3 |
Uncertainty factorsTable 17 - Footnote 3 |
30 |
Concentration (µg/m3) |
7000 |
Critical studyTable 17 - Footnote 4 |
1 |
Comments |
NOAELHEC = NOAEL x 5/7 days x 6/24 hours x 1 (RGDR) |
Organization | NON-NEOPLASTIC |
---|---|
US EPATable 18 - Footnote 1 | |
Year of publication |
1997 |
Species |
Rats |
Endpoint |
Effects on kidney |
Point of departure |
NOAEL = 2438 mg/m3 |
Uncertainty factorsTable 18 - Footnote 2 |
1000 |
Concentration (µg/m3) |
400 |
Critical studyTable 18 - Footnote 3 |
1 |
Comments |
NOAELHEC = PoD x 5/7 days x 6/24 hours x 1 (RGDR) |
Organization | NON-NEOPLASTIC |
---|---|
US EPATable 19 - Footnote 1 | |
Year of publication |
2003 |
Species |
Rats |
Endpoint |
Developmental effects |
Point of departure |
LEC10 = 5202 mg/m3 |
Uncertainty factorsTable 19 - Footnote 2 |
300 |
Concentration (µg/m3) |
5000 |
Critical studyTable 19 - Footnote 3 |
1, 2, 3 |
Comments |
LEC10 HEC = LEC10 x 7/24 hours |
Organization | NON-NEOPLASTIC |
---|---|
US EPATable 20 - Footnote 1 | |
Year of publication |
2003 |
Species |
Rats and mice |
Endpoint |
Developmental effects |
Point of departure |
NOAEL = 4100 mg/m3 |
Uncertainty factorsTable 20 - Footnote 2 |
300 |
Concentration (µg/m3) |
3000 |
Critical studyTable 20 - Footnote 3 |
1 |
Comments |
NOAELHEC = PoD x 6/24 hours x 1 (RGDR) |
Organization | NON-NEOPLASTIC |
---|---|
US EPATable 21 - Footnote 1 | |
Year of publication |
2008 |
Species |
Rats |
Endpoint |
Olfactory epithelium atrophy |
Point of departure |
LOAEL = 357 mg/m3 |
Uncertainty factorsTable 21 - Footnote 2 |
1000 |
Concentration (µg/m3) |
8 |
Critical studyTable 21 - Footnote 3 |
1 |
Comments |
BCMLHEC 10 = BMCL10 x 7/7 days x 6/24 hours x 0.26 (RGDR) |
Organization | NEOPLASTIC | NON-NEOPLASTIC | ||
---|---|---|---|---|
CalEPA | US EPATable 22 - Footnote 1 | CalEPA | US EPA | |
Year of publication |
1990 |
1990 |
||
Species |
Mice |
Mice |
Rats |
Rats |
Endpoint |
Nasal cavity tumours |
Nasal cavity tumours |
Atrophy of olfactory epithelium and degeneration of respiratory epithelium |
Atrophy of olfactory epithelium and degeneration of respiratory epithelium |
Unit risk (µg/m3)-1 |
3.7 x 10-6 |
3.7 x 10-6 |
- | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
2.7 |
2.7 |
- | - |
Point of departure |
- | - | LOAEL = 71 mg/m3 |
LOAEL = 71 mg/m3 |
Uncertainty factorsTable 22 - Footnote 3 |
- | - | 100 |
100 |
Concentration (µg/m3) |
- | - | 30 |
30 |
Critical studyTable 22 - Footnote 4 |
1, 2 |
1, 2 |
3 |
3 |
Comments |
- | - | LOAELHEC = LOAEL x 5/7 days x 6/24 hours x 0.23 (RGDR) |
LOAELHEC = LOAEL x 5/7 days x 6/24 hours x 0.23 (RGDR) |
OrganizationTable 23 - Footnote 1 | NON-NEOPLASTIC | |||||
---|---|---|---|---|---|---|
ATSDRTable 23 - Footnote 2 | CalEPA | Health Canada | RIVM | US EPA | WHO | |
Year of publication |
2010 |
1993 |
2001 |
1992 |
2000 |
|
Species |
Humans |
Humans |
Rats |
Humans |
Humans |
Humans |
Endpoint |
Neurotoxicity |
Neurotoxicity |
Body weight change; neurotoxicity |
Neurotoxicity |
Neurotoxicity |
Neurotoxicity |
Unit risk (µg/m3)-1 |
- | - | - | - | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
- | - | - | - | - | - |
Point of departure |
LOAEL = 85.2 mg/m3 |
BMCL05 = 7.2 mg/m3 |
LOEL = 260 mg/m3 |
LOAEL = 107 mg/m3 |
NOAEL = 106 mg/m3 |
LOAEL = 107 mg/m3 |
Uncertainty factorsTable 23 - Footnote 4 |
30 |
3 |
500 |
30 |
30 |
100 |
Concentration (µg/m3) |
850 |
900 |
92 |
900 |
1000 |
260 |
Critical studyTable 23 - Footnote 5 |
1 |
2 |
3, 4 |
2* |
2 |
2 |
Comments |
LOAELADJ = LOAEL x 8 hours/24 hours x 5 days/7 days |
BMCL05ADJ = BMCL05 x 10 m3/20 m3 x 5 days/7 days |
LOELADJ = LOEL x 6 hours/24 hours |
LOAELADJ = LOAEL x 8 hours/24 hours x 5 days/7 days *RIVM does not explicitly cite a critical study. It is likely Mutti et al. (1984) . |
Lower 95% confidence limit of the NOAEL = NOAEL x 0.88 |
LOAEL adjusted by a factor of 4.2 to convert from occupational to continuous exposure |
OrganizationTable 24 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | |||||
---|---|---|---|---|---|---|---|
CalEPA | US EPA | ATSDR | Health Canada | RIVM | US EPATable 24 - Footnote 2 | WHO | |
Year of publication |
2012 |
2014 |
1993 |
2001 |
2012 |
2010 |
|
Species |
Mice |
Mice |
Humans |
Mice |
Humans |
Humans |
Humans |
Endpoint |
Liver tumours |
Liver tumours |
Neurobehavioral effects |
Nephrotoxicity, hepatotoxicity |
Nephrotoxicity |
Neurotoxicity, visual impairment |
Nephrotoxicity |
Unit risk (µg/m3)-1 |
5.9 x 10-6 |
2.6 x 10-7 |
- | - | - | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
1.7 |
40 |
- | - | - | - | - |
Point of departure |
- | - | LOAEL = 50.3 mg/m3 |
LOAEL = 678 mg/m3 |
LOAEL = 100 mg/m3 |
From two studies: |
LOAEL = 100 mg/m3 |
Uncertainty factorsTable 24 - Footnote 4 |
- | - | 300 |
1000 |
100 |
1000 |
100 |
Concentration (µg/m3) |
- | - | 40 |
360 |
250 |
40 |
250 |
Critical studyTable 24 - Footnote 5 |
1 |
2 |
3, 4 |
1 |
5 |
3, 6 |
5 |
Comments |
- | Unit risk calculated using PBPK modelling |
LOAELADJ = LOAEL x 5/7 days x 8/24 hours |
LOAELADJ = LOAEL x 5/7 days x 6/24 hours x 3 (volume/body weight adjustment of mice to humans) |
LOAELADJ = LOAEL x 40 hr/week/168 hr week |
LOAELADJ = LOAEL x 5/7 days x 10/20 m3/d, breathing rate. |
LOAELADJ = LOAEL x 40 hr/week / 168 hr week |
Organization | NEOPLASTIC | NON-NEOPLASTIC | ||
---|---|---|---|---|
CalEPA | ATSDR | CalEPATable 25 - Footnote 1 | US EPA | |
Year of publication |
2015 |
2016 |
1995 |
|
Species |
Rats |
Humans |
Humans |
Humans |
Endpoint |
Subcutaneous fibroma/fibrosarcoma |
Decreased lung function |
Decreased lung function |
Decreased lung function |
Unit risk (µg/m3)-1 |
1.1 x 10‑5 |
- | - | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
0.91 |
- | - | - |
Point of departure |
- | AEL = 0.0085 mg/m3 |
NOAEL = 0.006 mg/m3 |
NOAEL = 0.006 mg/m3 |
Uncertainty factorsTable 25 - Footnote 3 |
- | 100 |
300 |
30 |
Concentration (µg/m3) |
- | 0.02 |
0.008 |
0.07 |
Critical studyTable 25 - Footnote 4 |
1 |
2 |
3 |
3 |
Comments |
Inhalation unit risk derived from an oral cancer potency factor in male rats exposed by gavage to a commercial mixture of toluene diisocyanate |
AELADJ = AEL x 5/7 days x 8/24 hours |
NOAELADJ = NOAEL x 10 m3/20 m3 x 5 days/7 days |
NOAELADJ = NOAEL x 10 m3/20 m3 x 5 days/7 days US EPA has medium confidence in the study, database and RfC. |
OrganizationTable 26 - Footnote 1 | NON-NEOPLASTIC | |||||
---|---|---|---|---|---|---|
ATSDR | CalEPA | Health Canada | RIVM | US EPATable 26 - Footnote 2 | VCCEP | |
Year of publication |
2007 |
1993 |
2001 |
2003 |
2005 |
|
Species |
Humans |
Humans |
Rats |
Rats |
Rats |
Rats |
Endpoint |
Symptoms of neurotoxicity, sore throat, nose, and eye irritation |
Symptoms of neurotoxicity, sore throat, nose, and eye irritation |
Unspecified maternal effects and fetal skeletal retardation |
Decreased rotarod performance in offspring |
Decreased latency in paw-lick response (i.e., sensitivity to pain) |
Decreased rotarod performance in males (i.e., decreased motor activity) |
Point of departure |
LOAEL = 61 mg/m3 |
LOAEL = 61 mg/m3 |
LOEL = 250 mg/m3 |
LOAEL = 870 mg/m3 |
LOAEL = 434 mg/m3 |
LOAEL = 434 mg/m3 |
Uncertainty factorsTable 26 - Footnote 4 |
300 |
30 |
1000 |
1000 |
300 |
100 |
Concentration (µg/m3) |
220 |
700 |
180 |
870 |
100 |
660 |
Critical studyTable 26 - Footnote 5 |
1 |
1 |
2 |
3 |
4 |
4 |
Comments |
UFDB for lack of chronic neurotoxicity data |
Continuous exposure adjustment: multiplied PoD by [(10 m3/d)/ (20 m3/d) x 5 d/7 d] |
0.72 applied to PoD to account for inhalation volume/body weight of young rats relative to humans (i.e., rats [(0.11 m3/day)/0.35 kg] to humans aged 5 to 11 years [(12 m3/day)/27 kg). |
- | NOAELHEC = NOAEL x 5/7 days x 6/24 hours |
NOAELADJ = NOAEL x 6/24 hours x 5/7 days NOAELHEC = NOAELADJ X 1.7 (RGDR) |
7.0 Tables of TRVs for individual VOCs (no IARLSs recommended)
Organization | NEOPLASTIC |
---|---|
CalEPA | |
Year of publication |
|
Species |
Mice |
Endpoint |
Liver tumours |
Unit risk (µg/m3)-1 |
5.8 x 10-5 |
Concentration at 1 x 10-5 risk level (µg/m3) |
0.17 |
Critical studyTable 27 - Footnote 2 |
1 |
CommentsTable 27 - Footnote 3 |
Based on a US EPA oral slope factor. US EPA did not derive an inhalation slope factor. |
OrganizationTable 28 - Footnote 1 | NEOPLASTIC | NON-NEOPLASTIC | |||
---|---|---|---|---|---|
CalEPA | RIVM | US EPA | ATSDR | CalEPA | |
Year of publication |
2001 |
1991 |
2001 |
2001 |
|
Species |
Rats |
Rats (assumed) |
Rats |
Rats |
Rats |
Endpoint |
Hemangiosarcomas |
Hemangiosarcomas |
Hemangiosarcomas |
No effects |
Effects on liver |
Unit risk (µg/m3)-1 |
2.1 x 10-5 |
2.1 x 10-6 |
2.6 x 10-5 |
- | - |
Concentration at 1 x 10-5 risk level (µg/m3) |
0.48 |
4.8 |
0.38 |
- | - |
Point of departure |
- | - | - | NOAEL = 222 mg/m3 |
NOAEL = 40 mg/m3 |
Uncertainty factorsTable 28 - Footnote 3 |
- | - | - | 90 |
30 |
Concentration (µg/m3) |
- | - | - | 2500 |
400 |
Critical studyTable 28 - Footnote 4 |
1 |
1, 2 |
1 |
3 |
4 |
CommentsTable 28 - Footnote 5 |
Based on gavage study |
Based on gavage study Assessment in Dutch; summary available only in English |
Based on gavage study As of 2000, under review by US EPA IRIS |
One dose, no control group |
NOAELHEC = PoD x 5/7 days x 7/24 hours x 1.5 (RGDR) |
Organization | NEOPLASTIC | NON-NEOPLASTIC |
---|---|---|
CalEPA | CalEPA | |
Year of publication |
||
Species |
Mice |
Guinea pigs |
Endpoint |
Liver tumours |
Ocular toxicity |
Unit risk (µg/m3)-1 |
4.6 x 10‑4 |
- |
Concentration at 1 x 10-5 risk level (µg/m3) |
0.02 |
- |
Point of departure |
- | LOAEL = 440 mg/m3 |
Uncertainty factorsTable 29 - Footnote 2 |
- | 3000 |
Concentration (µg/m3) |
- | 20 |
Critical studyTable 29 - Footnote 3 |
1 |
2 |
CommentsTable 29 - Footnote 4 |
Inhalation unit risk derived from an oral cancer potency factor in male mice exposed to 4,4’-methylenedianiline dihydrochloride in drinking water |
LOAELADJ = LOAEL x 4 hours/24 hours x 5 days/7 days |
OrganizationTable 30 - Footnote 1 | NON-NEOPLASTIC | |
---|---|---|
CalEPA | RIVM | |
Year of publication |
2001 |
|
Species |
Rats, mice, and monkeys |
Rats, mice, and monkeys |
Endpoint |
No effect on pulmonary, cardiovascular, hematological, hepatic or renal systems (NOAEL). |
Not reported |
Point of departure |
NOAEL = 20 mg/m3 |
NOAEC = 20 mg/m3 |
Uncertainty factorsTable 30 - Footnote 3 |
100 |
1000 |
Concentration (µg/m3) |
200 |
20 |
Critical studyTable 30 - Footnote 4 |
1, 2 |
(1) |
CommentsTable 30 - Footnote 5 |
NOAELHEC = NOAEL x 1 (RGDR) |
RIVM cited ATSDR (1998) as the source of the NOAEC. However, the updated ATSDR Toxicological Profile (2008) does not explicitly report a NOAEC and ATSDR considered the reviewed studies as inadequate. The NOAEC was likely derived from the summary of Sandage (1961) reported in ATSDR (1998). |
8.0 References
- Adams, E.M., Spencer, H.C., Rowe, V.K., McCollister, D.D. and Irish, D.D. (1952) Vapor toxicity of carbon tetrachloride determined by experiments on laboratory animals. Archives of Industrial Hygiene and Occupational Medicine, 6: 50-66.
- Aiso, S., Takeuchi, T., Arito, H., Nagano, K., Yamamoto, S. and Matsushima, T. (2005) Carcinogenicity and chronic toxicity in mice and rats exposed by inhalation to para-dichlorobenzene for two years. Journal of Veterinary Medical Science, 67(10): 1019-1029.
- Andrew, F.D., Buschbom, R.L., Cannon, W.C., Miller, R.A., Montgomery, L.F. and Phelps, D.W. (1981) Teratologic assessment of ethylbenzene and 2-ethoxyethanol. PB 83-208074, p.108, Battelle Pacific Northwest Laboratory, Richland, WA. *As cited in: US EPA IRIS database (1994).
- ATSDR (2014) Toxicological Profile for Tetrachloroethylene. Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services, Atlanta, GA. https://www.atsdr.cdc.gov/toxprofiles/tp18.pdf.
- ATSDR (2010) Toxicological Profile for Styrene. Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services, Atlanta, GA. https://www.atsdr.cdc.gov/toxprofiles/tp53.pdf.
- ATSDR (2006) Toxicological Profile for Dichlorobenzenes. Agency for Toxic Substances and Disease Registry, Public Health Service, US Department of Health and Human Services, http://www.atsdr.cdc.gov/toxprofiles/tp10.pdf.
- ATSDR (1994) Toxicological Profile for Acetone. Agency for Toxic Substances and Disease Registry, Public Health Service, US Department of Health and Human Services, Atlanta, GA http://www.atsdr.cdc.gov/toxprofiles/tp21.pdf.
- Baars, A.J., Theelen, R.M.C., Janssen, P.J.C.M., Hesse, J.M., van Apeldoorn, M.E., Meijerink, M.C.M., Verdam, L. and Zeilmaker, M.J. (2001) RIVM report 711701025. Re-evaluation of human-toxicological maximum permissible risk levels. RIVM. National Institute of Public Health and the Environment. Bilthoven, The Netherlands.
- Barbe, S.J., Terrill, J.B., DeSousa, D.J. and Conaway, C.C. (1984) Subchronic inhalation toxicology of ethylene glycol monoethyl ether in the rat and rabbit. Environmental Health Perspectives, 57:157-63.
- Benignus, V.A., Geller, A.M., Boyes, W.K. and Bushnell, P.J. (2005) Human neurobehavioral effects of long-term exposure to styrene: a meta-analysis. Environmental Health Perspectives, 113(5): 532-8.
- Bomski, H., Sobolewska, A. and Strakowski, A. (1967) Toxic damage of the liver by chloroform in chemical industrial workers. Arch Gewerbepathol Gewerbehy, 24(2): 127-134 *As cited in US EPA (2001).
- Burleigh-Flayer, H., Garman, R., Neptun, D., Bevan, C., Gardiner, T., Kapp, R., Tyler, T. and Wright, G. (1997) Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1 mice. Fundamental and Applied Toxicology, 36(2): 95-111.
- CalEPA (2016) Appendix D1. Air Toxics Hot Spot Program - Toluene Diisocyanate Reference Exposure Levels. California Environmental Protection Agency, Sacramento, CA., http://oehha.ca.gov/media/downloads/air/report-hot-spots/finaltdirelmarch2016.pdf.
- CalEPA (2015) Appendix L. Air Toxics Hot Spot Program - Guidance manual for Preparation of Health Risk Assessments - OEHHA/ARB Health Values for Use in Hot Spot Facility Risk Assessments. California Environmental Protection Agency, Sacramento, CA., http://oehha.ca.gov/media/downloads/crnr/2015gmappendiceslm.pdf.
- CalEPA (2014a) Appendix D1. Air Toxics Hot Spot Program - Summaries using this version of the hots spots risk assessment guidelines. California Environmental Protection Agency, Sacramento, CA., http://oehha.ca.gov/media/downloads/crnr/appendixd1final.pdf.
- CalEPA (2014b) Appendix D3. Air Toxics Hot Spot Program - Chronic RELs and toxicity summaries using the previous version of the hot spots risk assessment guidelines. California Environmental Protection Agency, Sacramento, CA., http://oehha.ca.gov/media/downloads/crnr/appendixd3final.pdf.
- CalEPA (2011) Appendix B. Air Toxics Hot Spot Program - Chemical-specific summaries of the information used to derive unit risk and cancer potency values. California Environmental Protection Agency, Sacramento, CA., http://oehha.ca.gov/media/downloads/crnr/appendixb.pdf.
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- Vermeire, T.G., van Apeldorn, M.E., de Fouw, J.C. and Janssen, P.J.C.M. (1991) Voorstel voor de human-toxicologische onderbouwing van C-toestsingswaarden. National Institute of Public Health and the Environment. RIVM Report No. 725201005, Bilthoven, The Netherlands. *As cited in Baars (2001).
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