Indoor Air Reference Levels for Chronic Exposure to Volatile Organic Compounds
Water and Air Quality Bureau
Health Canada
Table of contents
- List of tables
- List of acronyms
- Context
- 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 of indoor air reference levels
- 5.0 Indoor air reference levels
- 6.0 Tables of TRVs for individual VOCs
- 7.0 References
List of tables
- Table 1. Indoor Air Reference Levels
- Toxicological reference values for 1,1-dichloroethylene (CAS RN 75-35-4) (added 2023)
- Toxicological reference values for trans-1,2-dichloroethylene (CAS RN 156-60-5) (added 2023)
- Toxicological reference values for 1,3-butadiene (CAS RN 106-99-0)
- Toxicological reference values for 1,4-dichlorobenzene (CAS RN 106-46-7)
- Toxicological reference values for 1,4-dioxane (CAS RN 123-91-1) (added 2023)
- Toxicological reference values for 2-butoxyethanol (CAS RN 111-76-2) (Updated 2023)
- Toxicological reference values for 2-ethoxyethanol (CAS RN 110-80-5)
- Toxicological reference values for 2-ethylhexanol (CAS RN 104-76-7) (added 2023)
- Toxicological reference values for 3-chloropropene (CAS RN 107-05-1)
- Toxicological reference values for acetone (CAS No. 67-64-1)
- Toxicological reference values for ammonia (CAS RN 7664-41-7) (added 2023)
- Toxicological reference values for aniline (CAS RN 62-53-3)
- Toxicological reference values for carbon tetrachloride (CAS RN 56-23-5)
- Toxicological reference values for chloroform (CAS RN 67-66-3)
- Toxicological reference values for cyclohexane (CAS RN 110-82-7)
- Toxicological reference values for dichloromethane (CAS RN 75-09-2)
- Toxicological reference values for epichlorohydrin (CAS RN 106-89-8)
- Toxicological reference values for ethylbenzene (CAS RN 100-41-4)
- Toxicological reference values for ethylene oxide (CAS RN 75-21-8) (updated 2023)
- Toxicological reference values for isopropyl alcohol (CAS RN 67-63-0)
- Toxicological reference values for isopropylbenzene (CAS RN 98-82-8)
- Toxicological reference values for methyl ethyl ketone (CAS RN 78-93-3)
- Toxicological reference values for methyl isobutyl ketone (CAS RN 108-10-1)
- Toxicological reference values for propionaldehyde (CAS RN 123-38-6)
- Toxicological reference values for n-propylbromide (CAS RN 106-94-5) (added 2023)
- Toxicological reference values for propylene oxide (CAS RN 75-56-9)
- Toxicological reference values for styrene (CAS RN 100-42-5)
- Toxicological reference values for tetrachloroethylene (CAS RN 127-18-4)
- Toxicological reference values for toluene diisocyanate (mixed isomers) (CAS RN 26471-62-5) (updated 2023)
- Cancer toxicological reference values for trichloroethylene (CAS RN 79-01-6) (added 2023)
- Non-cancer toxicological reference values for trichloroethylene (CAS RN 79-01-6) (added 2023)
- Toxicological reference values for vinyl chloride (CAS RN 75-01-4) (added 2023)
List of acronyms
- ANSES
- Agence nationale de sécurité sanitaire, de l'alimentation, de l'environnement et du travail (France)
- ATSDR
- Agency for Toxic Substances and Disease Registry
- BMC
- benchmark concentration
- BMCL
- 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)
- CAS RN
- Chemical Abstract Service registry number
- 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
- MRL
- minimal risk level
- NOAEL
- no observed adverse effect level
- OEHHA
PBPK - California Office of Environmental Health Hazard Assessment
physiologically based pharmacokinetics - 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 in The Netherlands
- 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
Context
The purpose of this document is to present Health Canada's Indoor Air Reference Levels (IARLs). IARLs are health-based screening values developed for volatile organic compounds (VOCs) that were identified through partner and stakeholder consultation, from Government of Canada priorities, and/or are found in indoor air in Canada. IARLs are selected from available toxicological reference values (TRVs) from authoritative health and environmental organizations. They are associated with an acceptable level of risk following long-term exposure (over several months or years) in non-occupational scenarios for each specific VOC, as determined by the organization that performed the risk assessment. IARLs are selected for VOCs that are not addressed by Residential Indoor Air Quality Guidelines (RIAQG) and may be used to support risk assessment, risk management, and research needs of Health Canada, our partners and stakeholders.
1.0 Introduction
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.
To assist public health professionals who may need to assess the possible risk from exposure to VOCs potentially found in indoor air, Health Canada has selected Indoor Air Reference Levels (IARLs). For a given VOC, the IARL is an estimate of a concentration 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 an acceptable excess cancer risk level of 1 in 105. The IARL applies to the general population, including biologically susceptible subgroups.
IARLs are intended to supplement Health Canada's Residential Indoor Air Quality Guidelines (RIAQGs), which are based on comprehensive literature reviews, are externally peer-reviewed, and are posted for public consultation. In developing IARLs, the Health Canada review is limited to hazard assessments from internationally recognized health and environmental organizations and the key studies, as described in these assessments. Health Canada did not perform any new risk assessments for the IARLs, but rather selected the most relevant reference level derived by other organizations.
This document provides a summary of IARLs —current as of April 2023—for chronic exposure to VOCs. It includes IARLs first published in 2017 as well as new IARLs developed for contaminants identified through the Health Canada Indoor Air Program partner and stakeholder consultation and prioritization processes (Health Canada 2023a). Both new IARL candidates and contaminants with existing IARLs were subject to an initial selection process to determine whether they were suitable for development of a new IARL or an update of the existing IARL.
This document, along with the selected 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 supplementary document entitled Derivation of Health Canada Indoor Air Reference Levels: Methodology for Volatile Organic Compounds (Health Canada 2023b), which is available upon request. The methodology describes criteria for selection of candidates, identification of appropriate hazard assessments, and evaluation of hazard assessments based on the strength of the underlying science as well as consistency with Health Canada risk assessment practices for indoor air pollutants. Information on the derivation of individual IARLs is available upon request.
2.0 Considerations in the determination of indoor air reference levels
Authoritative health and environmental agencies and organizations, including Health Canada, follow similar procedures for conducting hazard assessments for cancer and non-cancer endpoints. Many hazard assessments are used to derive TRVs. The TRV nomenclature varies among the different organizations and includes terms such as reference concentration (RfC), tolerable concentration (TC), and minimal risk level (MRL). All TRVs considered in the selection of an IARL provide a quantitative value below which adverse non-cancer health effects are not expected to be observed for durations of up to a lifetime of exposure and include consideration of highly exposed and susceptible subpopulations. For non-threshold carcinogenic effects, the TRVs may be referred to as cancer potency factors, slope factors, or inhalation unit risks. For these TRVs, the level of potential excess lifetime cancer risk that would be considered acceptable is determined. For the purpose of IARLs, an excess cancer risk level of 1 in 105 is retained, which is consistent with many other health and environmental agencies and organizations.
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 then typically selected based on the most conservative value of either the identified cancer or non-cancer TRVs but might vary depending on the mode of action of the VOC or other considerations. The full list of IARLs is presented in section 5.0.
3.0 Application of indoor air reference levels
The IARL methodology provides an expedited means of generating health-based quantitative exposure limits for priority contaminants that are present in an indoor environment, are of concern for Health Canada Indoor Air Program partners and stakeholders, and/or are departmental priorities. IARLs can provide scientific support for risk assessment, risk management, and research activities of Health Canada, partners and stakeholders, including:
- the development of product emission standards and regulations for building materials and consumer products
- the development of guides and guidance for professional and non-professional audiences
- the provision of advice to the general public and public health professionals for reducing exposure to indoor air contaminants
- the identification of VOCs that may be appropriate for development of a RIAQG or other risk assessment activities
- the interpretation of data (such as measured or modelled concentrations) in the context of a human health risk assessment in a variety of exposure scenarios
For human health risk assessment applications, when comparing measured or modelled concentrations with IARLs, a statistically significant sample size with a sampling time of at least 24 hours taken under normal conditions is recommended. Averaging of results of repeated samples taken at different times of the year will provide a more representative estimate of the average long-term exposure. In some cases, the mode of action of a particular substance may also justify the use of samples of short durations and their consideration in risk assessment. In general, and especially where these conditions cannot be met, professional judgement should be used to consider all uncertainties that may impact a conclusion of potential risk.
4.0 Uncertainties and assumptions of indoor air reference levels
The IARL selection process has been developed to provide screening values for priority VOCs in an efficient manner. However, as Health Canada did not conduct a full human health risk assessment supported by a comprehensive review of all available data for each VOC, uncertainties are inherent in the IARL process. The first uncertainty arises due to the selection of TRVs derived by health and environmental agencies outside of Health Canada. A concerted effort was made to select high-quality TRVs from authoritative agencies that use risk assessment practices that are compatible with those employed by the Health Canada Indoor Air Program. Nevertheless, each agency has its own approach and policies that may result in a TRV that differs from one that Health Canada would have derived, given the same information. The second uncertainty arises from the date of derivation of the TRVs under consideration and literature search cut-off dates of each assessment. The IARL process considers the date of the TRV derivation and whether key studies were available at the time of derivation. However, in most cases, this information comes from within the assessments themselves as a literature search is not normally conducted as part of the IARL process. In addition, as with most risk assessments, there may be studies not captured by the risk assessment or more recent studies published after the assessment that could change the outcome.
In general, all hazard assessments must consider the uncertainties in the underlying toxicological and epidemiological data. Uncertainty factors, exposure adjustments, and chemical-specific data are used in a precautionary manner to address key assumptions. This approach results in 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 uncertainties inherent in measuring or estimating indoor air concentrations in homes in Canada. Indoor air concentrations measured in homes in Canada can be expected to vary based on factors such as the type, location, and housing characteristics, occupant behaviours, and averaging time of air measurements. Likewise, indoor air concentrations modelled based on VOC emissions observed from products, either in homes or in chamber tests, may differ from actual indoor air concentrations due to factors such as the number, type, pattern of use, and age of source materials; the rate of decay of the emissions over time; and environmental conditions (such as temperature, humidity, ventilation rate).
Given these uncertainties, comparison of estimated or measured indoor air concentrations with an IARL provides an indication of potential risk and not a measure of actual risk. The current list of IARLs is restricted to values for long-term (or lifetime) exposure and thus caution should be exercised when comparing an IARL with measured values from a single sample or multiple samples collected over a short period of time. VOC levels measured in indoor environments demonstrate a high level of temporal variability based on multiple factors such as seasonal changes. Best practises for the application of IARLs to human health risk assessment include comparison to a statistically significant sample size with a sampling time of at least 24 hours taken under normal conditions, and averaging the results of repeated samples taken at different times of the year to provide a more representative estimate of the long-term exposure. In some cases, the mode of action of a particular substance may also justify the use of samples of short durations and their consideration in risk assessment. Such data may not be available under certain circumstances, such as a contaminated, remote, or hard-to-access site. In such circumstances, the use of either fewer measurements or measurements of shorter duration may be unavoidable, and it is recommended to apply the maximum measured value to assess potential human health risks. Professional judgement should be used to consider how the associated uncertainties may impact conclusions. Health-based limits such as IARLs are best used to help identify sources of contaminants, to help identify the potential need to conduct further risk assessment activities, and/or to employ risk mitigation strategies to reduce exposure.
5.0 Indoor air reference levels
Table 1 summarizes the IARLs selected for 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.
Further information on the derivation of each IARL is available upon request (air@hc-sc.gc.ca).
| VOC | CAS RN | IARL (µg/m3) |
Critical Effect | Reference | IARL Date | |
|---|---|---|---|---|---|---|
| Cancer | Non-Cancer | |||||
| 1,1-Dichloroethylene | 75-35-4 | 0.06 | Kidney tumours | n/a | OEHHA (2017) | 2023 |
| trans-1,2-Dichloroethylene | 156-60-5 | 40 | n/a | Immunotoxicity | US EPA (2020a) | 2023 |
| 1,3-Butadiene | 106-99-0 | 1.7 | Leukemia | n/a | EC/HC (2000) | 2017Footnote 1 |
| 1,4-Dichlorobenzene | 106-46-7 | 60 | n/a | Nasal lesions | ATSDR (2006a) | 2017Footnote 1 |
| 1,4-Dioxane | 123-91-1 | 2 | Tumours at multiple sites | n/a | US EPA (2013) | 2023 |
| 2-Butoxyethanol | 111-76-2 | 82 | n/a | Nasal lesions | OEHHA (2018) | 2023 (updated) |
| 2-Ethoxyethanol | 110-80-5 | 70 | n/a | Testicular degeneration and hematological changes | OEHHA (2000)Footnote 2 | 2017Footnote 1 |
| 2-Ethylhexanol | 104-76-7 | 0.4 | n/a | Altered olfactory epithelia | US EPA (2019) | 2023 |
| 3-Chloropropene | 107-05-1 | 1 | n/a | Peripheral nerve damage | US EPA (1991a) | 2017Footnote 1 |
| Acetone | 67-64-1 | 70 000 | n/a | Developmental effects | VCCEP (2003) | 2017Footnote 1 |
| Ammonia | 7664-41-7 | 500 | n/a | Respiratory symptoms, altered lung function | US EPA (2016a) | 2023 |
| Aniline | 62-53-3 | 1 | n/a | Effects on spleen | US EPA (1990a) | 2017Footnote 1 |
| Carbon tetrachloride | 56-23-5 | 1.7 | Adrenal gland tumours | n/a | US EPA (2010a) | 2017Footnote 1 |
| Chloroform | 67-66-3 | 300 | n/a | Kidney and liver toxicity | OEHHA (2000)Footnote 2 | 2017Footnote 1 |
| Cyclohexane | 110-82-7 | 6000 | n/a | Reduced pup weight | US EPA (2003a) | 2017Footnote 1 |
| Dichloromethane | 75-09-2 | 600 | n/a | Effects on liver | US EPA (2011a) | 2017Footnote 1 |
| Epichlorohydrin | 106-89-8 | 1 | n/a | Histological changes in the nose | US EPA (1994a) | 2017Footnote 1 |
| Ethylbenzene | 100-41-4 | 2000 | n/a | Effects on pituitary gland and liver | OEHHA (2000)Footnote 2 | 2017Footnote 1 |
| Ethylene oxide | 75-21-8 | 0.002 | Lymphoid and breast cancer | n/a | US EPA (2016b) | 2023 (updated) |
| Isopropyl alcohol | 67-63-0 | 7000 | n/a | Kidney lesions | OEHHA (2000)Footnote 2 | 2017Footnote 1 |
| Isopropylbenzene | 98-82-8 | 400 | n/a | Effects on kidney | US EPA (1997) | 2017Footnote 1 |
| Methyl ethyl ketone | 78-93-3 | 5000 | n/a | Developmental effects | US EPA (2003b) | 2017Footnote 1 |
| Methyl isobutyl ketone | 108-10-1 | 3000 | n/a | Developmental effects | US EPA (2003c) | 2017Footnote 1 |
| Propionaldehyde | 123-38-6 | 8 | n/a | Olfactory epithelium atrophy | US EPA (2008) | 2017Footnote 1 |
| n-Propylbromide | 106-94-5 | 1.7 | n/a | Neurotoxicity | OEHHA (2022a) | 2023 |
| Propylene oxide | 75-56-9 | 2.7 | Nasal cavity tumours | n/a | US EPA (1990b) | 2017Footnote 1 |
| Styrene | 100-42-5 | 850 | n/a | Neurotoxicity | ATSDR (2010a) | 2017Footnote 1 |
| Tetrachloroethylene | 127-18-4 | 40 | n/a | Neurotoxicity, visual impairment, and neurobehavioural effects | US EPA (2012), ATSDR (2014) | 2017Footnote 1 |
| Toluene diisocyanate | 26471-62-5 | 0.008 | n/a | Decreased lung function | OEHHA (2016) | 2023 (updated) |
| Trichloroethylene | 79-01-6 | 2 | Kidney tumours, liver tumours, non-Hodgkin's lymphomaFootnote 3 | Thymus and cardiac effectsFootnote 3 | US EPA (2011b) | 2023 |
| Vinyl Chloride | 75-01-4 | 1.1 | Liver tumours | n/a | US EPA (2000) | 2023 |
EC/HC, Environment Canada, Health Canada
|
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6.0 Tables of TRVs for individual VOCs
| Organization | Cancer | Non-cancer | ||||
|---|---|---|---|---|---|---|
| Health CanadaFootnote 1 | OEHHAFootnote 2 | ATSDR | OEHHA | TCEQ | US EPA | |
| Year of publication | 2013 | 2017 | 2022a | 2000Footnote 3 | 2007 | 2003d |
| Species | Mice | Mice | Rats | Guinea pigs | Rats, Squirrel monkeys, Beagle dogs | Rats |
| Endpoint | Pulmonary adenomas | Renal tubule adenoma or carcinoma in males | Nasal lesions (necrosis of olfactory epithelium) | Liver toxicity (mottled liver and increased enzymes) | Focal necrosis of the liver | Liver toxicity (minimal fatty change) |
| Unit risk | TC05 of 4.2 mg/m3 | Slope factor of 0.129 (mg/kg-day)-1 for male mice | n/a | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 0.8 | 0.06 | n/a | n/a | n/a | n/a |
| Point of departure | n/a | n/a | BMCL10 = 6.3 mg/m3 BMCLHEC-ADJBMCLHEC = 0.14 mg/m3 |
NOAEL = 20 mg/m3 | NOAEL= 101 mg/m3 | BMCL10 = 39 mg/m3 BMCL10HEC-ADJ= 6.9 mg/m3 |
| Uncertainty factors | n/a | n/a | 30 (UFH = 10, UFA = 3) | 300 (UFH = 10, UFA = 3, UFS = 10) | 300 (UFH = 10, UFA = 3, UFS = 10) | 30 (UFH = 10, UFA = 3) |
| Concentration (µg/m3) | n/a | n/a | 4 | 70 | 340 | 200 |
| Critical studyFootnote 4 | 2 | 1 | 1 | 3 | 3 | 4 |
| Comments | TC05 of 4.2 mg/m3 is 1/20 risk. Divide by 5000 to get total risk of 10-4 | The animal slope factor was converted by OEHHA to a slope factor of 0.80 (mg/kg-day)-1 for humans NSRL was presented as 0.88 µg/day for 10-5 risk. This converts to an air concentration of 0.06 µg/m3 assuming an inhalation rate of 15.1 m3 /day | BMCLHEC-ADJ= BMCL x 5/7 days x 7/24 hours x 0.13 Where 0.13 is the RGDRET (rat:human)5 Note that ATSDR used ppm for units. MRL = 0.001 ppm | n/a | Quast et al. 1986 was a supporting study | BMCL10HEC-ADJ = BMCL10 x 5/7 days x 7/24 hours |
NSRL, No significant Risk Level
|
||||||
| Organization | Non-cancer | ||
|---|---|---|---|
| ATSDRFootnote 1 | RIVMFootnote 2 | US EPAFootnote 3,Footnote 4 | |
| Year of publication | 1996 | 2001 | 2020a |
| Species | Rats | Rats | Rats |
| Endpoint | Fatty degeneration of liver | Fatty degeneration of liver, effects in lungs | Immunotoxicity (Decreased lymphocyte count) |
| Point of departure | LOAEL = 200 ppm (800 mg/m3) | LOAEL = 780 mg/m3 LOAELADJ = 185 mg/m3 |
BMCLHEC = 109 mg/m3 |
| Uncertainty factors | 1000 (UFH = 10, UFA = 10, UFL = 10) | 3000 (UFH = 10, UFA = 10, UFL = 10, UFS = 3) | 3000 (UFH = 10, UFA = 3, UFS = 10, UFD = 10) |
| Concentration (µg/m3) | 800 | 60 | 40 |
| Critical studyFootnote 5 | 1 | 1 | 2 |
| Comments | s/o | LOAELADJ = LOAEL x 5/7 days x 8/24 hours | BMCLHEC = BMCL x 5/7 days x 7/24 hours x 1 (default for RGDR as rat>human) |
|
|||
| Organization | Cancer | Non-cancer | |||
|---|---|---|---|---|---|
| Health CanadaFootnote 1,Footnote 2 | OEHHA | US EPA | OEHHA | US EPA | |
| Year of publication | 2000 | 1992Footnote 3 | 2002 | 2013Footnote 3 | 2002 |
| Species | Humans | Mice | Humans | Mice | Mice |
| Endpoint | Leukemia | Lung tumours | Leukemia | Ovarian atrophy | Ovarian atrophy |
| Unit risk (µg/m3)-1 | 5.9 x 10-6 | 1.7 x 10-4 | 3 x 10-5 | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 1.7 | 17 | 0.3 | n/a | n/a |
| Point of departure | n/a | n/a | n/a | BMCL05 HEC = 0.664 mg/m3 | BMCL10 HEC = 2 mg/m3 |
| Uncertainty factors | n/a | n/a | n/a | 300 (UFH = 10, UFA = 30) |
1000 (UFH = 10, UFA = 3, UFL = 10, UFDB = 3) |
| Concentration (µg/m3) | n/a | n/a | n/a | 2.2 | 2 |
| Critical studyFootnote 4 | 2 | 1 | 2 | 3 | 3 |
| Comments | TC01 = 1.7 mg/m3 Unit risk = (0.01)/TC01 | n/a | LEC01 = 300 µg/m3 with adjustments from Health Canada and further adjustment for cancer incidence not mortality. Factor of 2 applied to adjust for potential for females to be more susceptible. |
BMCL05 HEC: Benchmark concentration adjusted for continuous exposure and dosimetric differences between rats and humans (using PBPK model data): BMCL05 x 5/7 days x 6/24 hours x 1.68 DAF |
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.] BMCL10 based on 2 lower doses, adjusted for continuous exposure and time to response (5/7 days x 6/24 hours). ppm equivalence across species assumed (equal to RGDR = 1) UFDB mainly for lack of 2-generational reproductive and neurodevelopmental studies. |
|
|||||
| Organization | Cancer | Non-cancer | ||||
|---|---|---|---|---|---|---|
| OEHHA | ATSDRFootnote 1 | Health CanadaFootnote 2 | OEHHA | RIVMFootnote 3 | US EPA | |
| Year of publication | 1999Footnote 4 | 2006a | 1993a; 1996 | 20014 | 2001 | 1994b |
| Species | Mice | Rats | Rats | Rats | Rats | Rats |
| Endpoint | Liver tumours | Nasal lesions | Increased liver and kidney weights; increased urinary protein/coproporphyrin | 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 weight |
| Unit risk (µg/m3)-1 | 1.1 x 10-5 | n/a | n/a | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 0.9 | n/a | n/a | n/a | n/a | n/a |
| Point of departure | n/a | LOAEL = 450 mg/m3 NOAEL = 120 mg/m3 BMCL10 = 57 mg/m3 BMCL10 ADJ = 10 mg/m3 BMCL10 HEC = 1.6 mg/m3 |
LOAEL = 3000 mg/m3 NOAEL = 450 mg/m3 NOAELADJ = 67 mg/m3 NOAELHEC = 48 mg/m3 |
LOAEL = 900 mg/m3 NOAEL = 300 mg/m3 NOAELADJ = 78mg/m3 NOAELHEC = 78 mg/m3 |
LOAEL = 3000 mg/m3 NOAEL = 450 mg/m3 NOAELADJ = 67 mg/m3 |
LOAEL = 900 mg/m3 NOAEL = 300 mg/m3 NOAELADJ = 75 mg/m3 NOAELHEC = 75 mg/m3 |
| Uncertainty factors | n/a | 30 (UFH = 10, UFA = 3) |
500 (UFH = 10, UFA = 10, UFS = 5) |
100 (UFH = 10, UFA = 3, UFS = 3) |
100 (UFH = 10, UFA = 10) |
100 (UFH = 10, UFA = 3, UFS = 3) |
| Concentration (µg/m3) | n/a | 60 | 95 | 800 | 670 | 800 |
| Critical studyFootnote 5 | 1 | 2, 3 | 5 | 4 | 6 | 4 |
| Comments | n/a | BMCL10 HEC = BMCL10 x 5/7 days x 6/24 hours x 0.16 (RGDR) | NOAELHEC = NOAEL x 5/7 days x 6/24 hours x 0.71 (breathing rate adjustment) | NOAELHEC = NOAEL x 7/7 days x 6/24 hours x 1.0 (RGDR) | NOAELADJ = NOAEL x 5/7 days x 5/24 hours x 0.71 (breathing rate adjustment). Appears to be same critical study as Loeser and Litchfield (1983). |
NOAELHEC = NOAEL x 7/7 days x 6/24 hours |
|
||||||
| Organization | Cancer | Non-cancer | |||
|---|---|---|---|---|---|
| OEHHA | US EPAFootnote 1 | ATSDR | OEHHA | US EPA | |
| Year of publication | 2011 | 2013 | 2012 | 2000Footnote 2 | 2013 |
| Species | Mice | Rats | Rats | Rats | Rats |
| Endpoint | Hepatocellular carcinoma and adenoma | Multiple tumour sites | Atrophy of the olfactory epithelium | No effects (inhalation study) | Atrophy and respiratory metaplasia of the olfactory epithelium |
| Unit risk (µg/m3)-1 | 7.7 x 10-6 | 5 x 10-6 | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 1.3 | 2 | n/a | n/a | n/a |
| Point of departure | n/a | n/a | LOAEL = 180 mg/m3 LOAELHEC = 32 mg/m3 |
NOAEL= 400 mg/m3 NOAELHEC = 83 mg/m3 |
LOAEL = 180 mg/m3 LOAELHEC = 32.2 mg/m3 |
| Uncertainty factors | n/a | n/a | 300 (UFA= 3, UFL= 10, UFH=10) | 30 (UFA= 3, UFH= 10) | 1000 (UFA = 3, UFH = 10, UFL = 10, UFDB = 3) |
| Concentration (µg/m3) | n/a | n/a | 100 | 3000 | 30 |
| Critical studyFootnote 3 | 3 | 1 | 1 | 2 | 1 |
| Comments | Linear multistage model Cancer potencies were adjusted using the factors (x 104/90 weeks)1/3 and (bwh/bwa)1/3. Route-to-route extrapolation (oral-to-inhalation) assuming a human body weight of 70 kg and an inhalation rate of 20 m3 per day | Multi-tumour BMD analysis to determine the combined BMC10 and the BMCL10. BMCLHEC =BMCL x 6/24 hours x 5/7 days x 1 (where 1 is the default DAF) IUR = BMR / BMCLHEC, where the BMR was 0.1 | LOAELHEC = LOAEL x 6/24 hours x 5/7 days x 1 (where 1 is the default used when the ratio of animal to human blood: air partition coefficients is greater than 1) | NOAELHEC = NOAEL x 7/24 hours x 5/7 days x 1 (where 1 is the default ratio of animal to human blood: air partition coefficients) Supported by liver, kidney, and hematological effects in drinking water study (NCI 1978) | LOAELHEC = LOAEL x 6/24 hours x 5/7 days x 1 (where 1 is the default DAF) |
|
|||||
| Organization | Non-cancer | |||
|---|---|---|---|---|
| ATSDR | Health CanadaFootnote 1 | OEHHAFootnote 2 | US EPA | |
| Year of publication | 1998 | 2002 | 2018 | 2010b |
| Species | Humans | Rats | Rats | Rats |
| Endpoint | Hematological effects | Hematological effects | Hyaline degeneration of nasal olfactory epithelium | Hemosiderin deposition |
| Point of departure | NOAEL = 2.9 mg/m3 | BMC05 = 5.3 mg/m3 | BMCL05,HEC = 2.46 mg/m3 | BMCL10,HEC = 16 mg/m3 |
| Uncertainty factors | 3 (UFH = 3) |
0.5 (UFH = 10, UFA = 0.05) |
30 (UFH = 10, UFA = 3) |
10 (UFH = 10, UFA = 1, UFDB = 1) |
| Concentration (µg/m3) | 970 | 11 000 | 82 | 1600 |
| Critical studyFootnote 3 | 1 | 2 | 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 with rats. | UFA includes only the toxicodynamic portion, since the HEC accounted for toxicokinetics by use of the RGDR. | 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-cancer | ||
|---|---|---|---|
| OEHHAFootnote 1 | US EPA | WHO | |
| Year of publication | 2000Footnote 2 | 1991b | 2010a |
| Species | Rabbits | Rabbits | Rats |
| Endpoint | Testicular degeneration and hematological changes | Testicular degeneration and hematological changes | Teratogenicity (delayed ossification) and preimplantation loss |
| Point of departure | NOAEL = 380 mg/m3 NOAELADJ = 68 mg/m3 NOAELHEC = 68 mg/m3 |
NOAEL = 380 mg/m3 NOAELADJ = 68 mg/m3 NOAELHEC = 68 mg/m3 |
NOAEL = 40 mg/m3 NOAELADJ = 10 mg/m3 |
| Uncertainty factors | 1000 (UFH = 10, UFA = 10, UFS = 10) |
300 (UFH = 10, UFA = 3, UFS = 10) |
100 (UFH = 10, UFA = 10) |
| Concentration (µg/m3) | 70 | 200 | 100 |
| Critical studyFootnote 3 | 1 | 1 | 2, 3 |
| Comments | NOAELADJ = NOAEL x 6/24 hours x 5/7 days NOAELHEC = NOAELADJ x 1 (RGDR) | NOAELADJ = NOAEL x 6/24 hours x 5/7 days NOAELHEC = NOAELADJ x 1 (RGDR) US EPA has medium confidence in the study, database and RfC. | NOAELADJ = NOAEL x 6/24 hours |
|
|||
| Organization | Non-cancer |
|---|---|
| US EPAFootnote 1 | |
| Year of publication | 2019 |
| Species | Mice |
| Endpoint | Diameter increase in the Bowman's glands in olfactory epithelium |
| Point of departure | LOAEL = 116 mg/m3 LOAELADJ-HEC = 4.17 mg/m3 BMCL1SD (HEC) = 1.1 mg/m3 |
| Uncertainty factors | 3000 (UFA= 3, UFDB= 10, UFH= 10, UFS= 10) |
| Concentration (µg/m3) | 0.4 |
| Critical studyFootnote 2 | 1 |
| Comments | LOAELADJ-HEC = LOAEL x 5/7 days x 8/24 hours x RGDRET (mouse: human)Footnote 3 The BMCL1SD (HEC) was used as the POD |
|
|
| Organization | Cancer | Non-cancer |
|---|---|---|
| OEHHA | US EPAFootnote 1 | |
| Year of publication | 1999Footnote 2 | 1991a |
| 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 | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 1.67 | n/a |
| Point of departure | n/a | NOAEL = 17 mg/m3 NOAELADJ = 3.6 mg/m3 NOAELHEC = 3.6 mg/m3 |
| Uncertainty factors | n/a | 3000 (UFH = 10, UFA = 3, UFS = 10, UFDB = 10) |
| Concentration (µg/m3) | n/a | 1 |
| Critical studyFootnote 3 | 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. |
|
||
| Organization | Non-cancer | |
|---|---|---|
| ATSDR | VCCEPFootnote 1,Footnote 2 | |
| Year of publication | 1994 | 2003 |
| Species | Humans | Rats |
| Endpoint | Increased amplitude of visual evoked response | Decreased fetal body weight |
| Point of departure | LOAEL = 3000 mg/m3 | NOAEL = 5300 mg/m3 NOAELHEC = 2100 mg/m3 |
| Uncertainty factors | 100 (UFH = 10, UFL = 10) |
30 (UFH = 10, UFA = 3) |
| Concentration (µg/m3) | 31 000 | 70 000 |
| Critical studyFootnote 3 | 1 | 2 |
| Comments | n/a | NOAELHEC calculated using PBPK modelling |
|
||
| Organization | Non-cancer | |||
|---|---|---|---|---|
| ATSDR | OEHHA | TCEQ | US EPAFootnote 1 | |
| Year of publication | 2004 | 2000Footnote 2 | 2015 | 2016a |
| Species | Humans | Humans | Humans | Humans |
| Endpoint | Altered lung function, irritation | Altered lung function, irritation | Respiratory effects | Altered lung function, respiratory symptoms |
| Point of departure | NOAEL= 6500 µg/m3 NOAELADJ = 1500 µg/m3 |
NOAEL= 6500 µg/m3 NOAELADJ = 2300 µg/m3 |
NOAEL = 8800 µg/m3 NOAELADJ = 3200 µg/m3 |
NOAEL = 13 600 µg/m3 NOAELADJ = 4900 µg/m3 |
| Uncertainty factors | 30 (UFH= 10, UFDB= 3) | 10 (UFH = 10) | 10 (UFH = 10) | 10 (UFH = 10) |
| Concentration (µg/m3) | 71 | 200 | 320 | 500 |
| Critical studyFootnote 3 | 1 | 1 | 1 | 1 |
| Comments | NOAEL = mean TWA exposure concentration (9.2 ppm) NOAELADJ = NOAEL x 5/7 days x 8/24 hours |
NOAEL = mean TWA exposure concentration (9.2 ppm) NOAELADJ = NOAEL x 5/7 days x 10/20 m3/day |
NOAEL = high exposure group (12.5 ppm) NOAELADJ = NOAEL x 5/7 days x 10/20 m3/day |
NOAEL = 95% lower confidence bound of mean in the high exposure group NOAELADJ = NOAEL x 5/7 days x 10/20 m3/day |
|
||||
| Organization | Cancer | Non-cancer |
|---|---|---|
| OEHHA | US EPAFootnote 1 | |
| Year of publication | 1999Footnote 2 | 1990a |
| Species | Rats | Rats |
| Endpoint | Spleen tumours | Effects on spleen |
| Unit risk (µg/m3)-1 | 1.6 x 10-6 | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 6.25 | n/a |
| Point of departure | n/a | NOAEL = 19 mg/m3 NOAELADJ = 3.4 mg/m3 NOAELHEC = 3.4 mg/m3 |
| Uncertainty factors | n/a | 3000 (UFH = 10, UFA = 10, UFS = 10, UFDB = 3) |
| Concentration (µg/m3) | n/a | 1 |
| Critical studyFootnote 3 | 1 | 2, 3 |
| Comments | Based on a US EPA oral slope factor. US EPA (1990a) did not derive an inhalation unit risk. | NOAELADJ = NOAEL x 6/24 hours x 5/7 days NOAELHEC = NOAELADJ x 1 (RGDR) US EPA has low confidence in the study, database, and RfC. |
|
||
| Organization | Cancer | Non-cancer | |||||
|---|---|---|---|---|---|---|---|
| OEHHA | US EPAFootnote 1 | ATSDR | OEHHA | RIVMFootnote 2 | US EPA | WHO | |
| Year of publication | 1987Footnote 3 | 2010a | 2005 | 2001Footnote 3 | 2001 | 2010a | 1999a |
| 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 | n/a | n/a | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 0.24 | 1.7 | n/a | n/a | n/a | n/a | n/a |
| Point of departure | n/a | n/a | NOAEL = 32 mg/m3 NOAELHEC = 5.7 mg/m3 |
LOAEL = 32 mg/m3 LOAELHEC = 11 mg/m3 |
NOAEL = 32 mg/m3 NOAELHEC = 6.3 mg/m3 |
BMCL10 HEC = 14.3 mg/m3 | (1) NOAEL = 6.1 mg/m3 (2) NOAEL = 32 mg/m3; NOAELHEC = 6.7 mg/m3 (3) NOAEL = 32 mg/m3; NOAELHEC = 5.7 mg/m3 |
| Uncertainty factors | n/a | n/a | 30 (UFH = 10, UFA = 3) |
300 (UFH = 10, UFA = 3, UFL = 3, UFS = 3) |
100 (UFH = 10, UFA = 10) |
100 (UFH = 10; UFA = 3; UFDB = 3) |
(1) 1000 (UFH = 10, UFA = 10, UFS = 10) (2) 1000 (UFH = 10, UFA = 10, UFS = 10) (3) 500 (UFH = 10, UFA = 10, UFL = 5) |
| Concentration (µg/m3) | n/a | n/a | 190 | 40 | 60 | 100 | (1) 6.1 (2) 6.7 (3) 11.4 |
| Critical studyFootnote 4 | 1 | 2, 3 | 3 | 4 | 5 | 2, 3 | (1) 6 (2) 4 (3) 3 |
| Comments | Linear multistage procedure Single treated dose | BMD modelling with PBPK to get LEC10 from which unit risk was calculated. | NOAELHEC = NOAEL x 5/7 days x 6/24 hrs x 1 (RGDR) | LOAELHEC = LOAEL x 5/7 days x 7/24 hrs x 1.7 (RGDR) | NOAELHEC = NOAEL x 5/7 days x 7/24 hrs | BMD with PBPK to estimate BMDL10, converted to human equivalent. UFDB for lack of a reproductive study. |
Three TCs were derived based on three different studies. (3) UFL of 5 used for marginal effect instead of NOAEL. |
|
|||||||
| Organization | Cancer | Non-cancer | ||||
|---|---|---|---|---|---|---|
| Health CanadaFootnote 1 | OEHHA | US EPA | ATSDR | OEHHAFootnote 2 | RIVMFootnote 3 | |
| Year of publication | 2001a | 1990Footnote 4 | 2001 | 1997 | 20004 | 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 | n/a | 5.3 x 10-6 | 2.3 x 10-5 | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | n/a | 1.9 | 0.4 | n/a | n/a | n/a |
| Point of departure | n/a | n/a | n/a | LOAEL = 10 mg/m3 | LOAEL = 120 mg/m3 LOAELHEC = 75 mg/m3 |
NOAEL = 110 mg/m3 |
| Uncertainty factors | n/a | n/a | n/a | 100 (UFH = 10, UFL = 10) |
300 (UFH = 10, UFA = 3, UFL = 10) |
1000 (UFH = 10, UFA = 10, UFS = 10) |
| Concentration (µg/m3) | 147 000 | n/a | n/a | 100 | 300 | 100 |
| Critical studyFootnote 5 | 1 | 1, 2, 3, 4 | 2 | 5 | 6 | 6 |
| Comments | PBPK used to determine 3.9 mg/L per hour, the rate of metabolism associated with a 5% increase in tumour risk (TC05). Adjusted for lifetime to TC05 = 147 mg/m3. |
Linear multistage procedure with PBPK. Based on a 1990 California Department of Health Services analysis. |
Linearized multistage procedure, extra risk | n/a | LOAELHEC = LOAEL x 5/7 days x 7/24 hours x 3 (RGDR) OEHHA used a different part of the same study as RIVM. |
UFS for 4 hours/day, 5 days/week, 6-month exposure. RIVM used a different part of the same study as OEHHA. |
|
||||||
| Organization | Non-cancer |
|---|---|
| US EPA1 | |
| Year of publication | 2003a |
| Species | Rats |
| Endpoint | Reduced pup weight (F1 and F2 generations) |
| Point of departure | NOAEL = 6886 mg/m3 NOAELADJ = 1700 mg/m3 BMCL1sd2 = 1822 mg/m3 |
| Uncertainty factors | 300 (UFH = 10, UFA = 3, UFDB = 10) |
| Concentration (µg/m3) | 6000 |
| Critical study3 | 1, 2 |
| Comments | NOAELADJ = NOAEL x 6/24 hours x 1 (RGDR) UFDB for lack of data for chronic and developmental neurotoxicity studies |
|
|
| Organization | Cancer | Non-cancer | ||||||
|---|---|---|---|---|---|---|---|---|
| Health CanadaFootnote 1 | OEHHA | US EPA | ATSDR | ATSDR | OEHHA | RIVMFootnote 2 | US EPAFootnote 3 | |
| Year of publication | 1993b | 1989Footnote 4 | 2011a | 2000 | 2000 | 20003 | 2001 | 2011a |
| Species | Mice | Mice | Mice | Rats | Rats | Humans | Humans | Rats |
| Endpoint | Lung tumours | Lung tumours | Lung and liver tumours | Effects on liver | Effects on liver | Increased carboxyhemoglobin | Increased carboxyhemoglobin | Effects on liver |
| Unit risk (µg/m3)-1 | 2.3 x 10-8 | 1.0 x 10-6 | 1.0 x 10-8 | n/a | n/a | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 435 | 10 | 1000 | n/a | n/a | n/a | n/a | n/a |
| Point of departure | n/a | n/a | n/a | NOAEL = 170 mg/m3 NOAELADJ = 31 mg/m3 |
NOAEL = 170 mg/m3 NOAELADJ = 31 mg/m3 |
LOAEL = 139 000 μg/m3 LOAELADJ = 48 700 μg/m3 |
LOAEL = 90 mg/m3 LOAELADJ = 3 mg/m3 |
BMDL10 = 532 mg dichloromethane metabolized via CYP pathway/L liver tissue/day HEC1% = 17.2 mg/m3 |
| Uncertainty factors | n/a | n/a | n/a | 30 (UFH = 10, UFA = 3) |
30 (UFH = 10, UFA = 3) |
100 (UFH = 10, UFL = 10) |
1 | 30 (UFH = 3, UFA = 3, UFDB = 3) |
| Concentration (µg/m3) | n/a | n/a | n/a | 1000 | 1000 | 400 | 3000 | 600 |
| Critical studyFootnote 5 | 1, 2 | 1, 2 | 1, 2 | 3 | 3 | 4 | 4 | 3 |
| Comments | Based on the lowest PBPK modified TD0.05 value. | n/a | Application of age-dependent adjustment factors results in a 70-year risk of 1.7 x 10-8. | NOAELADJ = NOAEL x 5/7 days x 6/24 hours UFA = 3 because of consideration of RGDR (value of 1 used). COHb levels also increased >10% at 700 mg/m3. |
NOAELADJ = NOAEL x 5/7 days x 6/24 hours UFA = 3 because of consideration of RGDR (value of 1 used). COHb levels also increased >10% at 700 mg/m3. |
LOAELADJ = LOAEL x 5/7 days x [(10 m3/d)/(20 m3/d)] Limited subjects and exposure information. |
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. Limited subjects and exposure information. |
HEC1% determined by PBPK modelling of calculated BMDL10 value. Value of 600 µg/m3 was rounded from 573 µg/m3. |
|
||||||||
| Organization | Cancer | Non-cancer | ||
|---|---|---|---|---|
| OEHHA | US EPA | OEHHA | US EPAFootnote 1 | |
| Year of publication | 1999Footnote 2 | 1988 | 2001Footnote 2 | 1994a |
| 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 | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 0.43 | 8 | n/a | n/a |
| Point of departure | n/a | n/a | NOAEL = 19 mg/m3 NOAELADJ = 3.4 mg/m3 NOAELHEC = 0.31 mg/m3 |
NOAEL = 19 mg/m3 NOAELADJ = 3.4 mg/m3 NOAELHEC = 0.36 mg/m3 |
| Uncertainty factors | n/a | n/a | 100 (UFH =10, UFA = 3, UFS = 3) |
300 (UFH = 10, UFA = 3, UFS, DB = 10) |
| Concentration (µg/m3) | n/a | n/a | 3 | 1 |
| Critical studyFootnote 3 | 1 | 2 | 3 | 3 |
| Comments | Inhalation unit risk derived from oral cancer potency factor in male rats exposed via drinking water. Data from the Laskin et al. (1980) inhalation study were not retained due to the poor survival of the study animals (data considered to be less suitable for generating a cancer potency factor than the data from the Konishi et al. (1980) study). Relevance of forestomach tumours in rodents to humans is unclear and not well addressed in this assessment. |
n/a | NOAELADJ = NOAEL x 6/24 hours x 5/7 days NOAELHEC = NOAELADJ x 0.14 m3/day / 20 m3/day x 200 cm2/15 cm2 (based on rat data) | NOAELADJ = NOAEL x 6/24 hours x 5/7 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, the study, and the database. |
|
||||
| OrganizationFootnote 1 | Cancer | Non-cancer | ||||||
|---|---|---|---|---|---|---|---|---|
| OEHHA | VCCEP | ATSDR | OEHHAFootnote 1 | RIVMFootnote 2 | US EPA | VCCEP | ||
| Year of publication | 2007Footnote 3 | 2007 | 2010b | 2000Footnote 3 | 2001 | 1991c | 2007 | |
| Species | Rats | Mice | Rats | Rats and mice | Rats and mice | Rabbits | Rats | |
| Endpoint | Kidney tumours | Lung tumours | Effects on kidney | Effects on pituitary gland and liver (mice) | Effects on liver and kidney | Developmental effects | Auditory effects | |
| Unit risk (µg/m3)-1 | 2.5 x 10-6 | n/a | n/a | n/a | n/a | n/a | n/a | |
| Concentration at 1 x 10-5 risk level (µg/m3) | 4 | n/a | n/a | n/a | n/a | n/a | n/a | |
| Point of departure | n/a | 40 500 mg metabolized in lung/kg lung/wk | LOAEL = 330 mg/m3 | NOAEL = 330 mg/m3 NOAELADJ = 57 mg/m3 |
NOAEL = 430 mg/m3 NOAELADJ = 77 mg/m3 |
LOAEL = 4340 mg/m3 | LOEL = 860 mg/m3 LED0105Footnote 4 = 272.8 mg-h ethylbenzene/L RPTFootnote 5/wk |
|
| Uncertainty factors | n/a | 300 (UFH = 10, UFA = 3, UFseverity of lesion = 10) |
300 (UFH = 10, UFA = 3, UFL = 10) |
30 (UFH = 10, UFA = 3) |
100 (UFH = 10, UFA = 10) |
300 (UFH = 10, UFA = 3, UFS = 10) |
100 (UFH = 10, UFA = 3, UFS = 3) |
|
| Concentration (µg/m3) | n/a | 2100 | 260 | 2000 | 770 | 1000 | 1300 | |
| Critical studyFootnote 6 | 1 | 1 | 1 | 1, 2 | 3 | 4, 5 | 6 | |
| Comments | More recent evidence suggests ethylbenzene may be a threshold carcinogen. | n/a | 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 = NOAEL x 5/7 days x 6/24 hours Subchronic study |
US EPA has low confidence in this derivation; published prior to NTP (1999). | Subchronic study supportive of chronic effects. | |
|
||||||||
| Organization | Cancer | Non-cancer | ||||
|---|---|---|---|---|---|---|
| Health CanadaFootnote 1 | OEHHA | TCEQ | US EPAFootnote 2 | ATSDR | OEHHA | |
| Year of publication | 2001b | 1987Footnote 3 | 2020 | 2016b | 2022b | 2001Footnote 3 |
| Species | Rats | Rats | Humans | Humans | Rats | Mice |
| Endpoint | Mononuclear leukemia | Mononuclear leukemia | Lymphoid cancer | Lymphoid and breast cancer | Decreased pup body weight | Neurological effects |
| Unit risk (µg/m3)-1 | 2.3 x 10-5 | 8.8 x 10-5 | 2.3 x10-6 | 5.0 x 10-3 | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 0.43 | 0.11 | 4.3 | 0.002 | n/a | n/a |
| Point of departure | n/a | n/a | n/a | n/a | NOAEL = 18 mg/m3 NOAELADJ = 3.8 mg/m3 |
NOAEL = 18 mg/m3 NOAELADJ = 3.2 mg/m3 |
| Uncertainty factors | n/a | n/a | n/a | n/a | 30 (UFH = 10, UFA = 3) |
100 (UFH = 10, UFA = 3, UFS = 3) |
| Concentration (µg/m3) | n/a | n/a | n/a | n/a | 130 | 30 |
| Critical studyFootnote 4 | 2 | 1 | 3 | 3 | 4 | 2 |
| Comments | Unit risk of 2.3 x 10-5 (µg/m3)-1 estimated from TC05 value of 2.2 mg/m3 | Based on a 1985 US EPA analysis that considered human equivalent dose. | Age-dependent adjustment factors were applied to the adult UR. | 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 5.85/7 days x 6/24 hours Where 5.85 is the weighted average |
NOAELADJ = POD x 5/7 days x 6/24 hours |
|
||||||
| Organization | Non-cancer |
|---|---|
| OEHHAFootnote 1 | |
| Year of publication | 2000Footnote 2 |
| Species | Rats and mice |
| Endpoint | Kidney lesions |
| Point of departure | NOAEL = 1200 mg/m3 NOAELHEC = 220 mg/m3 |
| Uncertainty factors | 30 (UFH = 10, UFA = 3) |
| Concentration (µg/m3) | 7000 |
| Critical studyFootnote 3 | 1 |
| Comments | NOAELHEC = NOAEL x 5/7 days x 6/24 hours x 1 (RGDR) |
|
|
| Organization | Non-cancer |
|---|---|
| US EPAFootnote 1 | |
| Year of publication | 1997 |
| Species | Rats |
| Endpoint | Effects on kidney |
| Point of departure | NOAEL = 2438 mg/m3 NOAELHEC = 435 mg/m3 |
| Uncertainty factors | 1000 (UFH = 10, UFA = 10, UFS = 10) |
| Concentration (µg/m3) | 400 |
| Critical studyFootnote 2 | 1 |
| Comments | NOAELHEC = POD x 5/7 days x 6/24 hours x 1 (RGDR) |
|
|
| Organization | Non-cancer |
|---|---|
| US EPAFootnote 1 | |
| Year of publication | 2003b |
| Species | Rats |
| Endpoint | Developmental effects |
| Point of departure | LEC10 = 5202 mg/m3 LEC10 HEC = 1517 mg/m3 |
| Uncertainty factors | 300 (UFH = 10, UFA = 3, UFDB = 10) |
| Concentration (µg/m3) | 5000 |
| Critical studyFootnote 2 | 1, 2, 3 |
| Comments | LEC10 HEC = LEC10 x 7/24 hours UFDB for lack of developmental neurotoxicity data, chronic inhalation toxicity study, and multigeneration reproductive toxicity study. |
|
|
| Organization | Non-cancer |
|---|---|
| US EPAFootnote 1 | |
| Year of publication | 2003c |
| Species | Rats and mice |
| Endpoint | Developmental effects |
| Point of departure | NOAEL = 4100 mg/m3 NOAELHEC = 1026 mg/m3 |
| Uncertainty factors | 300 (UFH = 10, UFA = 3, UFDB = 10) |
| Concentration (µg/m3) | 3000 |
| Critical studyFootnote 2 | 1 |
| Comments | NOAELHEC = POD x 6/24 hours x 1 (RGDR). UFDB for lack of developmental neurotoxicity, neurotoxicity, and chronic toxicity studies. US EPA has low to medium confidence in this RfC. |
|
|
| Organization | Non-cancer |
|---|---|
| US EPA1 | |
| Year of publication | 2008 |
| Species | Rats |
| Endpoint | Olfactory epithelium atrophy |
| Point of departure | LOAEL = 357 mg/m3 BMCL10 = 128 mg/m3 BMCL10 HEC = 8.3 mg/m3 |
| Uncertainty factors | 1000 (UFH = 10, UFA = 3, UFS = 10, UFDB = 3) |
| Concentration (µg/m3) | 8 |
| Critical study2 | 1 |
| Comments | BCMLHEC 10 = BMCL10 x 7/7 days x 6/24 hours x 0.26 (RGDR) UFDB for lack of a 2-generation reproductive toxicity study. US EPA has medium confidence in the critical endpoint, low to medium confidence in the study selected, and low confidence in overall database. |
|
|
| Organization | Cancer | Non-cancer | |||
|---|---|---|---|---|---|
| OEHHA | US EPA | ATSDR | OEHHAFootnote 1 | US EPAFootnote 2 | |
| Year of publication | 2022b | 2020b | 2017 | 2022a | 2020b |
| Species | Mice | Mice | Humans (Epidemiological) | Humans (Epidemiological) | Rats |
| Endpoint | Combined alveolar/ bronchiolar adenoma or carcinoma in females | Combined alveolar/bronchiolar adenoma or carcinoma in females | Mild neurological impairment (decreased vibratory perception in feet) |
Reduction in distal peripheral nerve function (decreased vibratory perception in feet) |
Decreased traction time (time hanging from a suspended bar) |
| Unit risk (µg/m3)-1 | 3.7 x 10-6 | 1 x 10-6 | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 2.7 | 10 | n/a | n/a | n/a |
| Point of departure | n/a | n/a | LOAEL = 6.4 mg/m3 LOAELADJ = 2.3 mg/m3 |
LOAEL: 14.13 mg/m3 LOAELADJ = 5.05 mg/m3 |
BMCL1SD = 92 mg/m3 HEC(consumer exposure) = 30.5 mg/m3 |
| Uncertainty factors | n/a | n/a | 30 (UFL= 3, UFH = 10) | 3000 (UFL= √10, UFS = 10, UFH= 100) |
100 (UFA = 10, UFH = 10) |
| Concentration (µg/m3) | n/a | n/a | 100 | 1.7 | 300Footnote 3 |
| Critical studyFootnote 4 | 4 | 4 | 1 | 2 | 3 |
| Comments | n/a | n/a | LOAELADJ = LOAEL x 5/7 days x 12/24 hours) RELFootnote 5 is 0.02 ppm after rounding | LOAELADJ = LOAEL x 5/7 days x 10/20m3) UFH includes a toxicokinetic factor of 10 (to protect infants and children) and a toxicodynamic factor of 10 (for neurotoxicity) | HEC = BMCLx 8/24 hours) No TRV was derived. The UF of 100 was recommended to indicate a "target MOE" but not applied by US EPA An HEC of 30.5 mg/m3 was also determined using the BMCL1 of 116 mg/m3 for post-implantation loss in a 2-generation rat study, adjusted for continuous exposure (x6/24 hr) |
|
|||||
| Organization | Cancer | Non-cancer | ||
|---|---|---|---|---|
| OEHHA | US EPAFootnote 1 | OEHHA | US EPA | |
| Year of publication | 19992 | 1990b | 20002 | 1990b |
| 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 | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 2.7 | 2.7 | n/a | n/a |
| Point of departure | n/a | n/a | LOAEL = 71 mg/m3 LOAELHEC = 3 mg/m3 |
LOAEL = 71 mg/m3 LOAELHEC = 3 mg/m3 |
| Uncertainty factorsFootnote 2 | n/a | n/a | 100 (UFH = 10, UFA = 3, UFL = 3) |
100 (UFH = 10, UFA = 3, UFL = 3) |
| Concentration (µg/m3) | n/a | n/a | 30 | 30 |
| Critical studyFootnote 3 | 1, 2 | 1, 2 | 3 | 3 |
| Comments | n/a | n/a | LOAELHEC = LOAEL x 5/7 days x 6/24 hours x 0.23 (RGDR). US EPA concluded there was medium confidence in the study selected, dataset, and resulting RfC. |
LOAELHEC = LOAEL x 5/7 days x 6/24 hours x 0.23 (RGDR). No studies in mice at lower concentrations than those in NTP (1985) were identified. |
|
||||
| Organization | Non-cancer | |||||
|---|---|---|---|---|---|---|
| ATSDRFootnote 1 | Health CanadaFootnote 2 | OEHHA | RIVMFootnote 3 | US EPA | WHO | |
| Year of publication | 2010a | 1993c | 2000Footnote 4 | 2001 | 1992 | 2000 |
| Species | Humans | Rats | Humans | Humans | Humans | Humans |
| Endpoint | Neurotoxicity | Body weight change; neurotoxicity | Neurotoxicity | Neurotoxicity | Neurotoxicity | Neurotoxicity |
| Unit risk (µg/m3)-1 | n/a | n/a | n/a | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | n/a | n/a | n/a | n/a | n/a | n/a |
| Point of departure | LOAEL = 85.2 mg/m3 LOAELADJ = 20.4 mg/m3 |
LOEL = 260 mg/m3 LOELADJ = 65 mg/m3 LOELHEC = 46 mg/m3 |
BMCL05 = 7.2 mg/m3 BMCL05ADJ = 2.6 mg/m3 |
LOAEL = 107 mg/m3 LOAELADJ = 26 mg/m3 |
NOAEL = 106 mg/m3 Lower 95% confidence limit of the NOAEL = 94 mg/m3 NOAELADJ = 34 mg/m3 |
LOAEL = 107 mg/m3 LOAELADJ = 26 mg/m3 |
| Uncertainty factors | 30 (UFH = 10, UFL = 3) |
500 (UFH = 10, UFA = 10, UFL = 5) |
3 (UFH = 3) |
30 (UFH = 10, UFL = 3) |
30 (UFH = 3, UFDB = 3, UFS = 3) |
100 (UFH = 10, UFL = 10) |
| Concentration (µg/m3) | 850 | 92 | 900 | 900 | 1000 | 260 |
| Critical studyFootnote 5 | 1 | 3, 4 | 2 | 2* | 2 | 2 |
| Comments | LOAELADJ = LOAEL x 8/24 hours x 5/7 days | LOELADJ = LOEL x 6/24 hours LOELHEC = LOELADJ x [(0.11 m3/day/ 0.35 kg)/ (12 m3/day/27 kg)] |
BMCL05ADJ = BMCL05 x 10 m3/20 m3 x 5/7 days | LOAELADJ = LOAEL x 8/24 hours x 5/7 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 US EPA has medium confidence in the RfC and study, and medium to high confidence in the database. |
LOAEL adjusted by a factor of 4.2 to convert from occupational to continuous exposure. |
|
||||||
| Organization | Cancer | Non-cancer | |||||
|---|---|---|---|---|---|---|---|
| OEHHA | US EPA | ATSDR1 | Health CanadaFootnote 2 | RIVMFootnote 3 | US EPAFootnote 1 |
WHO | |
| Year of publication | 1991Footnote 4 | 2012 | 2014 | 1993d | 2001 | 2012 | 2010b |
| Species | Mice | Mice | Humans | Mice | Humans | Humans | Humans |
| Endpoint | Liver tumours | Liver tumours | Neurobehavioural effects | Nephrotoxicity, hepatotoxicity | Nephrotoxicity | Neurotoxicity, visual impairment | Nephrotoxicity |
| Unit risk (µg/m3)-1 | 5.9 x 10-6 | 2.6 x 10-7 | n/a | n/a | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 1.7 | 40 | n/a | n/a | n/a | n/a | n/a |
| Point of departure | n/a | n/a | LOAEL = 50.3 mg/m3 LOAELADJ = 12 mg/m3 |
LOAEL = 678 mg/m3 LOAELADJ = 360 mg/m3 |
LOAEL = 100 mg/m3 LOAELADJ = 25 mg/m3 |
From two studies: |
LOAEL = 100 mg/m3 LOAELADJ = 25 mg/m3 |
| Uncertainty factorsFootnote 4 | n/a | n/a | 300 (UFH = 10, UFL = 10, UFDB = 3) |
1000 (UFH = 10, UFA = 10, UFL = 10) |
100 (UFH = 10, UFL = 10) |
1000 |
100 (UFH = 10, UFL = 10) |
| Concentration (µg/m3) | n/a | n/a | 40 | 360 | 250 | 40 |
250 |
| Critical studyFootnote 5 | 1 | 2 | 3, 4 | 1 | 5 | 3, 6 |
5 |
| Comments | n/a | 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 | Cancer | Non-cancer | ||
|---|---|---|---|---|
| OEHHA | ATSDR | OEHHAFootnote 1 | US EPA | |
| Year of publication | 1999Footnote 2 | 2018 | 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 | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 0.91 | n/a | n/a | n/a |
| Point of departure | n/a | AELFootnote 3 = 0.0085 mg/m3 AELADJ = 0.00202 mg/m3 |
NOAEL = 0.006 mg/m3 NOAELADJ = 0.002 mg/m3 |
NOAEL = 0.006 mg/m3 |
| Uncertainty factors | n/a | 100 (UFH = 10, UFL = 10) |
300 (UFH = 100, UFS = 3) |
30 (UFH = 10, UFDB = 3) |
| Concentration (µg/m3) | n/a | 0.02 | 0.008 | 0.07 |
| Critical studyFootnote 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 5/7 days | NOAELADJ = NOAEL x 10 m3/20 m3 x 5/7 days US EPA has medium confidence in the study, database, and RfC. |
|
||||
| Organization | Cancer | |||||
|---|---|---|---|---|---|---|
| ANSES | Health Canada (DWG) | Health Canada (PSL) Footnote 1 | OEHHA | US EPAFootnote 2,Footnote 3 | WHO | |
| Year of publication | 2018 | 2005 | 1993e | 2011* | 2011b | 2010b* |
| Species | Human (epidemiological) | Rats | Rats | Mice | Human (epidemiological) | Rats |
| Endpoint | Kidney tumours | Renal tubular adenocarcinomas | Leydig cell tumours in testes | hepatocellular carcinomas, adenomas and hepatomas; pulmonary lymphomas and adenocarcinomas | Kidney tumours, non-Hodgkin's lymphoma, liver tumours | Leydig cell tumours in testes |
| Unit risk (µg/m3)-1 | 10-6 | 1.2 x 10-7 (males) 8.1 x 10-8 (females) |
6.1 x 10-7 | 2.0 x 10-6 | 4.1x 10-6 | 4.3 x 10-7 |
| Concentration at 1 x 10-5 risk level (µg/m3) | 10 | 83 (males) 120 (females) |
16 | 5 | 2 | 23 |
| Critical studyFootnote 4 | 5 | 1 | 1 | 1,2,3,4 | 5,6 | 7 |
| Comments | Based on the kidney cancer portion of the combined excess risk per unit calculated by the US EPA (2011). | Linearized multistage modelling. Body weight-based scaling was used: (bwa/bwh)1/4 | TC05 derived using multistage modelling. Adjusted for continuous exposure (7/24 hours, 5/7 days). Scaled based on inhalation volume to bw ratio. |
Linearized multistage modelling; PBPK modelling; geometric mean of IUR for 4 studies. |
IUR= 0.01/ LEC0.1 |
*IUR derived in 2000. |
DWG, Drinking Water Guidelines, PSL, Priority Substances List
|
||||||
| Organization | Non-cancer | ||||
|---|---|---|---|---|---|
| ANSES | Health Canada (DWG) | OEHHA | RIVMFootnote 1 | US EPAFootnote 2,Footnote 3 | |
| Year of publication | 2018 | 2005 | 2000Footnote 4 | 2001 | 2011b |
| Species | Rats | Rats | Humans (epidemiological) | Mice | Mice and rats |
| Endpoint | Renal Toxicity | Fetal heart malformations | Symptoms of neurotoxicity (drowsiness, fatigue, headache); eye irritation | Hepatotoxicity | Decreased thymus weight (mice); fetal heart malformations (rat) |
| Point of departure | BMCL = 238 ppm BMCL HEC-ADJ= 43.7 ppm | BMCL10= 146 µg/kg bw per day | LOAEL: 170 mg/m3 LOAELADJ = 60 mg/m3 |
LOAEL= 200 mg/m3 | Mouse: Rat: |
| Uncertainty factors | 75 (UFA= 2.5; UFH=10; UFDB=3) | 100 (UFH = 10 UFA = 10) |
100 (UFH = 10 UFL = 10) |
1000 (UFA= 10; UFH= 10; UFL = 10) |
Mouse: 100 (UFA= 3; UFH= 3; UFL = 10) |
| Concentration (µg/m3) | 3.2 | 5 | 600 | 200 | Mouse: 1.9 |
| Critical studyFootnote 5 | 7 | 11 | 10 | 12 | 8,9 |
| Comments | BMCLADJ = BMCL x 5/7 days x 7/ 24 hours HEC was determined by PBPK modelling (dose metric = blood concentration of metabolite DCVC) |
The TDI of 1.46 µg/kg bw per day was converted to an air concentration by IACAS (2013). |
LOAELADJ = LOAEL x 5/7 days x 10/20 m3/day |
n/a | HEC99-LOAEL and HEC99-BMDL01 were determined by PKPB modelling Overall RfC was the midpoint between 2 candidate RfCs. |
DWG, Drinking Water Guidelines
|
|||||
| Organization | Cancer | Non-cancer | |||||
|---|---|---|---|---|---|---|---|
| ANSES | OEHHA | US EPAFootnote 1 | WHO | ATSDRFootnote 2 | US EPA | TCEQ | |
| Year of publication | 2012 | 2000 | 2000 | 1999b | 2006b | 2000 | 2009 |
| Species | Mice | Mice | Rats | Human | Rats | Rats | Rats |
| Endpoint | Liver angiosarcoma and hepatocellular carcinomas | Lung carcinoma | Liver angiosarcoma, angioma, hepatoma, or neoplastic nodules |
All cancers | Hepatic centrilobular hypertrophy | Liver cell polymorphism and cysts | Centrilobular hypertrophy in the liver |
| Unit risk (µg/m3)-1 | 3.8 x 10-6 | 7.7 x 10-5 | For continuous lifetime exposure from birth: For continuous lifetime exposure through adulthood: |
1 x 10-6 (estimate) | n/a | n/a | n/a |
| Concentration at 1 x 10-5 risk level (µg/m3) | 2.6 | 0.13 | For continuous lifetime exposure from birth: 1.1 For continuous lifetime exposure through adulthood: 2.3 |
10 | n/a | n/a | n/a |
| Point of departure | n/a | n/a | n/a | n/a | LEC10= 5.08 ppm HEC = 1 ppm |
HEC: 2.5mg/m3 LOAEL: 25.3 mg/m3 |
PODADJ (BMCL10) = 0.680ppm |
| Uncertainty factorsFootnote 3 | n/a | n/a | n/a | n/a | n/a | 30 (UFH = 10; UFA = 3) |
30 (UFA= 3;UFH = 10; UFL= 1) |
| Concentration (µg/m3) | n/a | n/a | n/a | n/a | 80 | 100 | 60 |
| Critical studyFootnote 4 | 4 | 5 | 1 | 6,7 | 3 | 2 | 3 |
| Comments | n/a | n/a | Linearized multistage modelling was used to derive the unit risk |
n/a | Intermediate MRL (15–364 days) | The inhalation RfC was derived from an oral exposure study: Til et al. 1983. | Study was chosen due to its publishing date and the study design. |
|
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7.0 References
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- US EPA (1991a) Allyl chloride; (CASRN 107-05-1)). Integrated Risk Information System (IRIS) Chemical Assessment Summary. United States Environmental Protection Agency, Washington, DC. Available at: http://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0387_summary.pdf
- US EPA (1991b) 2-Ethoxyethanol; CASRN 110-80-5. Integrated Risk Information System (IRIS) Chemical Assessment Summary. United States Environmental Protection Agency, Washington, DC. Available at: https://iris.epa.gov/static/pdfs/0513_summary.pdf
- US EPA (1991c) Ethylbenzene; CASRN 100-41-4. Integrated Risk Information System (IRIS) Chemical Assessment Summary. US Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0051_summary.pdf
- US EPA (1992) Styrene; CASRN 100-42-5. Integrated Risk Information System (IRIS) Chemical Assessment Summary. United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0104_summary.pdf
- US EPA (1994a) Epichlorohydrin (CASRN 106-89-8). Integrated Risk Information System (IRIS). Chemical Assessment Summary. United States Environmental Protection Agency, Washington, DC. Available at: http://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0050_summary.pdf
- US EPA (1994b) 1,4-Dichlorobenzene; CASRN 106-46-7. Integrated Risk Information System (IRIS) Chemical Assessment Summary. United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0552_summary.pdf
- US EPA (1994c) Data evaluation report: Ethylene oxide (EtO): Range-finding/developmental studies in rats (MRID #427977-01 and -02). D192811. Two generation reproduction study in rats (MRID# 427881-01). D192453 (Previous 189547). U.S. Environmental Protection Agency.
- US EPA (1995) 2,4-/2,6-Toluene diisocyanate mixture (TDI); CASRN 26471-62-5. Integrated Risk Information System (IRIS) Chemical Assessment Summary. US Environmental Protection Agency, Washington, DC. Available at: https://iris.epa.gov/static/pdfs/0503_summary.pdf
- US EPA (1997) Toxicological Review of Cumene (Isopropyl Benzene) (CAS No. 98-82-8). In support of summary information on the integrated risk information system (IRIS). United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0306tr.pdf
- US EPA (2000) Toxicological Review of Vinyl Chloride (CASRN 75-01-4). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635R-00/004, US Environmental Protection Agency, Washington, DC. Available at: https://iris.epa.gov/static/pdfs/1001tr.pdf
- US EPA (2001) Toxicological Review of Chloroform (CAS No. 67-66-3). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-01/001, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/si/si_public_record_Report.cfm?Lab=NCEA&dirEntryId=200258
- US EPA (2002) Health Assessment Of 1,3-Butadiene. EPA/600/P-98/001F, U.S. Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/si/si_public_record_report.cfm?Lab=NCEA&dirEntryId=54499
- US EPA (2003a) Toxicological Review of Cyclohexane (CAS No. 100-82-7). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-03/008, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/1005tr.pdf
- US EPA (2003b) Toxicological Review of Methyl Ethyl Ketone (CAS No. 78-93-3). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA 635/R-03/009, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0071tr.pdf
- US EPA (2003c) Toxicological Review of Methyl Isobutyl Ketone (CAS No. 108-10-1). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-03/002, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0173tr.pdf
- US EPA (2003d) 1,1-Dichloroethylene (1,1-DCE); CASRN: 75-35-4. Integrated Risk Information System (IRIS) Chemical Assessment Summary. United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/subst/0039_summary.pdf
- US EPA (2008) Toxicological Review of Propionaldehyde (CAS No. 123-38-6). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-08/003F, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/1011tr.pdf
- US EPA (2010a) Toxicological Review of Carbon Tetrachloride (CAS No. 56-23-5). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-08/005F, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0020tr.pdf
- US EPA (2010b) Toxicological Review of Ethylene Glycol Monobutyl Ether (EGBE) (CAS No. 111-76-2). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-08/006F, United States Environmental Protection Agency, Washington, DC. Available at: https://iris.epa.gov/static/pdfs/0500tr.pdf
- US EPA (2011a) Toxicological Review of Dichloromethane (Methylene Chloride). (CAS No. 75-09-2). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-10/003F, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0070tr.pdf
- US EPA (2011b) Review of Tricloroethylene (CAS No. 79-01-6). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-09/011F, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0199tr.pdf
- US EPA (2012) Toxicological Review of Tetrachloroethylene (Perchloroethylene) (CAS No. 127-18-4). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-08/011F, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0106tr.pdf
- US EPA (2013) Toxicological Review of 1,4-Dioxane (with inhalation update) (CASRN 123-91-1). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-11/003F, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0326tr.pdf
- US EPA (2016a) Toxicological Review of Ammonia – Non-Cancer Inhalation (CASRN 7664-41-7). Integrated Risk Information System (IRIS). EPA/635/R-16/163Fa, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/0422tr.pdf
- US EPA (2016b) Evaluation of the Inhalation Carcinogenicity of Ethylene Oxide (CAS No. 75-21-8). In Support of Summary Information on the Integrated Risk Information System (IRIS). EPA/635/R-16/350Fa, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/iris/iris_documents/documents/toxreviews/1025tr.pdf
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- US EPA (2020a) Provisional Peer-Reviewed Toxicity Values for trans-1,2-Dichloroethylene (CAS RN 156-60-5). EPA/690/R-19/001F, United States Environmental Protection Agency, Washington, DC. Available at: https://cfpub.epa.gov/ncea/pprtv/recordisplay.cfm?deid=349934
- US EPA (2020b) Risk Evaluation for 1-Bromopropane (n-Propyl Bromide) CASRN: 106-94-5. 740-R1-8013, U.S. Environmental Protection Agency, Washington, DC. Available at: https://www.epa.gov/sites/default/files/2020-08/documents/risk_evaluation_for_1-bromopropane_n-propyl_bromide.pdf
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- VCCEP (2007) Tier 1 pilot submission for ethylbenzene (Cas No. 100-41-4). Voluntary Children's Chemical Evaluation Program, Washington, DC. Available at: https://www.tera.org/Peer/VCCEP/Ethylbenzene/EBWelcome.html
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- WHO (1999a) Carbon Tetrachloride. Environmental Health Criteria 208. World Health Organization, Geneva, Switzerland. Available at: https://www.inchem.org/documents/ehc/ehc/ehc208.htm
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- WHO (2000) Chapter 5.12—Styrene. In Air quality guidelines for Europe, 2nd edition. WHO Regional Publications, Copenhagen, Denmark. Available at: https://www.who.int/publications-detail-redirect/9789289013581
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Footnotes
- Footnote 1
-
Definitions of VOCs are often tailored to a specific application or regulatory context, and therefore may diverge from a strict chemical definition based on vapour pressure.
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