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

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).

Table 1. Indoor Air Reference Levels
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

Footnote 1

Not updated in 2023 as no new TRVs were identified.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA (2011, 2014a, 2014b, 2015).

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Footnote 3

TRVs for non-cancer and cancer effects for trichloroethylene were close enough to be considered equivalent.

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6.0 Tables of TRVs for individual VOCs

Toxicological reference values for 1,1-dichloroethylene (CAS RN 75-35-4) (added 2023)
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

Footnote 1

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (2013).

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Footnote 2

The OEHHA cancer TRV was retained as the IARL.

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Footnote 3

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA report 2014b.

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Footnote 4

1. NTP (2015): 14-week and 2-year inhalation study. 2. Maltoni et al. (1984a, 1985): 1-year inhalation study.3. Prendergast et al. (1967): 90-day continuous inhalation study. 4. Quast et al. (1986): 18-month inhalation study. 5 RGDRET (rat: human) = regional gas dose ratio (rat:human) for the extrathoracic region of the respiratory tract.

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Toxicological reference values for trans-1,2-dichloroethylene (CAS RN 156-60-5) (added 2023)
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)
Footnote 1

ATSDR derived an intermediate MRL.

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Footnote 2

RIVM derived a provisional TC. The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 3

The US EPA TRV was retained as the IARL.

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Footnote 4

The US EPA derived a screening level provisional RfC.

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Footnote 5

1. Freundt et al. (1977): 8- and 16-week inhalation study; 2. Kelly (1998): 90-day inhalation study.

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Toxicological reference values for 1,3-butadiene (CAS RN 106-99-0)
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.
Footnote 1

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (2000).

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Footnote 2

The Health Canada TRV was retained as the IARL: The same database was used for the US EPA and Health Canada cancer assessments, but the Health Canada TRV was selected as it used a methodology that was considered to be more consistent with Indoor Air Program practices.

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Footnote 3

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 4

1. Melnick et al. (1990): 2-year inhalation study; 2. Delzell et al. (1995): retrospective cohort; 3. NTP (1993): 2-year inhalation study.

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Toxicological reference values for 1,4-dichlorobenzene (CAS RN 106-46-7)
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
Footnote 1

The ATSDR TRV was retained as the IARL: Linear low-dose extrapolation was not considered appropriate for a non-genotoxic carcinogen; therefore, the cancer TRV from OEHHA was not selected as the IARL. For the non-cancer endpoint, the ATSDR TRV was selected as it used a recent chronic inhalation study that was not available at the time of the other assessments.

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Footnote 2

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (1993a) and Health Canada (1996).

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Footnote 3

The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 4

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 5

1. NTP (1987): 2-year gavage study; 2. Aiso et al. (2005): 2-year inhalation study; 3. Japan Bioassay Research Center (1995): 2-year inhalation study; 4. Chlorobenzene Producers Association (1986): 2-generation reproductive inhalation study; 5. Loeser and Litchfield (1983): 2-year inhalation study; 6. Riley et al. (1980): 2-year inhalation study.

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Toxicological reference values for 1,4-dioxane (CAS RN 123-91-1) (added 2023)
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)
Footnote 1

The US EPA cancer TRV was retained as the IARL: The cancer TRV from the US EPA assessment was selected as it used a more recent inhalation study, compared with the older oral study used by the OEHHA. The US EPA assessment was also more recent and incorporated mode of action data.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA report 2014b.

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Footnote 3

1. Kasai et al. (2009): 2-year inhalation study; 2. Torkelson et al. (1974): 2-year inhalation study; 3. National Cancer Institute (1978): 90-week drinking water study.

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Toxicological reference values for 2-butoxyethanol (CAS RN 111-76-2) (Updated 2023)
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.
Footnote 1

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (2002).

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Footnote 2

The OEHHA TRV was retained as the IARL.

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Footnote 3

1. Haufroid et al. (1997) : occupational study; 2. NTP (1998, 2000): 2-year inhalation study.

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Toxicological reference values for 2-ethoxyethanol (CAS RN 110-80-5)
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
Footnote 1

The OEHHA TRV was retained as the IARL.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2014a, 2014b, 2015).

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Footnote 3

1. Barbe et al. (1984): 13-week inhalation study; 2/3. Tinston et al. (1983); Doe (1984): gestation day 6–15 developmental inhalation study.

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Toxicological reference values for 2-ethylhexanol (CAS RN 104-76-7) (added 2023)
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
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

1. Miyake et al. (2016): 3-month inhalation study.

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Footnote 3

RGDRET (mouse: human) = regional gas dose ratio (mouse:human) for the extrathoracic region of the respiratory tract.

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Toxicological reference values for 3-chloropropene (CAS RN 107-05-1)
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.
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2015).

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Footnote 3

1. NCI (1977): 78-week ingestion study (gavage); 2. Lu et al. (1982): 3-month inhalation study.

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Toxicological reference values for acetone (CAS No. 67-64-1)
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
Footnote 1

The VCCEP assessment was published under the authorship of the American Chemistry Council Acetone Panel (2003).

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Footnote 2

The VCCEP TRV was retained as the IARL: The TRV from the ATSDR assessment was not considered appropriate as the key study had significant weaknesses, and the US EPA considered it insufficient for deriving an RfC. A Health Canada assessment also considered the 6-week study used by ATSDR as indicative of short-term rather than long-term effects. Therefore the value derived by the VCCEP was selected as the IARL.

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Footnote 3

1. Stewart et al. (1975): 6-week controlled human exposure study; 2. Mast et al. (1988): 2-generation reproductive inhalation study.

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Toxicological reference values for ammonia (CAS RN 7664-41-7) (added 2023)
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
Footnote 1

The US EPA TRV was retained as the IARL: All of the TRVs were based on the same key study but used different methods for determining the point of departure. The US EPA used the frequency distribution of the exposure data to estimate the mean of the high exposure group and its 95% lower confidence bound, which was then used to derive the TRV; this comprehensive assessment was also the most recent and was therefore selected for the IARL.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA report 2014b.

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Footnote 3

1. Holness et al. (1989): occupational study.

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Toxicological reference values for aniline (CAS RN 62-53-3)
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.
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2015).

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Footnote 3

1. CIIT (1982): 2-year ingestion study; 2.Oberst et al. (1956): 20- to 26-week inhalation study; 3. E.I. DuPont de Nemours and Company Inc. (1982): 2-week inhalation study.

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Toxicological reference values for carbon tetrachloride (CAS RN 56-23-5)
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.
Footnote 1

The US EPA cancer TRV was retained as the IARL: The US EPA cancer TRV was selected as the IARL as it was based on a more recent inhalation study compared with the older, oral study used by the OEHHA.

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Footnote 2

The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 3

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 4

1. Edwards and Dalton (1942): 8-month gavage study (only 4-month exposure); 2. Nagano et al. (2007): 2-year inhalation study; 3. Japan Bioassay Research Center (1998): 2-year inhalation study; 4. Adams et al. (1952): 7-month inhalation study; 5. Vermeire et al. (1991): summary report; 6. Prendergast (1967): 90-day inhalation study.

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Toxicological reference values for chloroform (CAS RN 67-66-3)
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.
Footnote 1

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (2001a).

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Footnote 2

The OEHHA non-cancer TRV was retained as the IARL: Linear extrapolation was not considered appropriate for this non-genotoxic carcinogen. For non-cancer effects, a clearer point of departure could be determined from the animal study compared with the human study. The LOAEL identified by OEHHA for 7-hour per day exposure was considered more appropriate than the NOAEL identified by RIVM for 4-hour per day exposure.

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Footnote 3

The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 4

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 5

1. Jorgenson et al. (1985): 2-year drinking water study; 2. NCI (1976): 78-week gavage study; 3. Roe et al. (1979): 80-week study in toothpaste; 4. Tumasonis et al. (1985): 2-year drinking water study; 5. Bomski et al. (1967): 1- to 4-year occupational case-control study; 6. Torkelson et al. (1976): 6-month inhalation study.

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Toxicological reference values for cyclohexane (CAS RN 110-82-7)
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
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

BMCL1sd(HEC): benchmark concentration lower limit of a 1-sided 95% confidence interval for 1 standard deviation; human equivalent concentration.

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Footnote 3

1,2. DuPont HLR (1997); Kreckmann et al. (2000): 2-generation reproductive inhalation study.

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Toxicological reference values for dichloromethane (CAS RN 75-09-2)
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.
Footnote 1

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (1993b).

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Footnote 2

The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 3

The US EPA non-cancer TRV was retained as the IARL: The US EPA assessments were the most recent and included BMD modelling and refinements to the PBPK model. The use of rat data for the non-cancer TRV was also considered more appropriate than those that used human data due to issues of study quality (that is., a low number of subjects and limited exposure information in the human studies).

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Footnote 4

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 5

1. NTP (1986b): 2-year inhalation study; 2. Mennear et al. (1988): 2-year inhalation study; 3. Nitschke et al. (1988): 2-year inhalation study; 4. DiVincenzo and Kaplan (1981): 5-day occupational inhalation study.

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Toxicological reference values for epichlorohydrin (CAS RN 106-89-8)
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.
Footnote 1

The US EPA non-cancer TRV was retained as the IARL: Tumours are related to exposure route; therefore the OEHHA cancer assessment based on forestomach tumours observed in an oral study was not considered appropriate for the IARL; the nasal tumours resulting from inhalation exposure were considered a more relevant endpoint.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 3

1. Konishi et al. (1980): 81-week ingestion study (drinking water); 2. Laskin et al. (1980): 30-day inhalation study; 3. Quast et al. (1979): 90-day inhalation study (whole body).

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Toxicological reference values for ethylbenzene (CAS RN 100-41-4)
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.
Footnote 1

The OEHHA non-cancer TRV was retained as the IARL: Linear low-dose extrapolation was not considered appropriate for a non-genotoxic carcinogen; therefore the cancer TRV from OEHHA was not selected. The non-cancer TRV from OEHHA was selected as the IARL as the key study was of chronic duration, with relevant endpoints.

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Footnote 2

The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 3

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 4

LED0105: the 95% upper confidence limit on the lowest effective dose resulting in a loss of 1.05% percent of outer hair cells in the cochlea.

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Footnote 5

RPT: richly perfused tissue.

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Footnote 6

1. NTP (1999): 2-year inhalation study; 2. Chan et al. (1998): 2-year inhalation study; 3. NTP (1992): 13-week inhalation study; 4. Andrew et al. (1981): gestation days 1–19 and 1–24, developmental study; 5. Hardin et al. (1981): gestation days 1–19 and 1–24, developmental study; 6. Gagnaire et al. (2007): 13-week inhalation study.

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Toxicological reference values for ethylene oxide (CAS RN 75-21-8) (updated 2023)
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
Footnote 1

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (2001b).

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Footnote 2

The US EPA TRV was retained as the IARL.

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Footnote 3

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 4

1. Snellings et al. (1981): 2-year inhalation study; 2. Snellings et al. (1984): 10- or 11-week inhalation study; 3. Steenland et al. (2003, 2004): retrospective cohort; 4. US EPA 1994c: 2-generation inhalation study.

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Toxicological reference values for isopropyl alcohol (CAS RN 67-63-0)
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)
Footnote 1

The OEHHA TRV was retained as the IARL.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA report (2014a, 2014b, 2015).

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Footnote 3

1.Burleigh-Flayer et al. (1997): 78-week (mice) or 2-year (rat) inhalation study.

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Toxicological reference values for isopropylbenzene (CAS RN 98-82-8)
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)
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

1. Cushman et al. (1995): 13-week inhalation study.

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Toxicological reference values for methyl ethyl ketone (CAS RN 78-93-3)
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.
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

1. Schwetz et al. (1991): gestation day 6–15 developmental inhalation study; 2. Mast et al. (1989): gestation day 6–15 developmental inhalation study; 3. NTP (1990): gestation day 6–15 developmental inhalation study.

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Toxicological reference values for methyl isobutyl ketone (CAS RN 108-10-1)
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.
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

1. Tyl et al. (1987): gestation day 6–15 developmental inhalation study.

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Toxicological reference values for propionaldehyde (CAS RN 123-38-6)
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.
Footnote 1

The US EPA TRV was retained as the IARL.

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Footnote 2

1. Union Carbide (1993): inhalation developmental study.

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Toxicological reference values for n-propylbromide (CAS RN 106-94-5) (added 2023)
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)
Footnote 1

The OEHHA non-cancer TRV was retained as the IARL.

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Footnote 2

The US EPA published a risk assessment of 1-Bromopropane (2020b) but did not derive any TRVs.

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Footnote 3

The value shown is what a TRV could be if the proposed uncertainty factors were applied to the HEC, but the US EPA 2020b assessment did not include an actual TRV derivation.

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Footnote 4

1. Li et al. (2010a): occupational study; 2. Li et al. (2010b): occupational study; 3. Honma et al. (2003): 3-week inhalation study; 4. NTP (2011): 105-week inhalation study.

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Footnote 5

REL: recommended exposure limit

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Toxicological reference values for propylene oxide (CAS RN 75-56-9)
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.

Footnote 1

The US EPA non-cancer TRV was retained as the IARL: OEHHA adopted the cancer unit risk from the US EPA.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2014a, 2014b, 2015).

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Footnote 3

1. NTP (1985): 2-year inhalation study; 2. Renne et al. (1986): 2-year inhalation study; 3. Kuper et al. (1988): 2-year inhalation study.

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Toxicological reference values for styrene (CAS RN 100-42-5)
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
NOAELADJ = lower 95% confidence limit of NOAEL x 10 m3/20 m3 x 5/7 days.

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.
Footnote 1

The ASTDR TRV was retained as the IARL: The ATSDR TRV was selected as the IARL as the assessment is the most recent, and the TRV is derived from a meta-analysis using data from nine studies.

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Footnote 2

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (1993c).

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Footnote 3

The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 4

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2014a, 2014b, 2015).

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Footnote 5

1. Benignus et al. (2005): meta-analysis of several occupational studies; 2. Mutti et al. (1984): occupational study (average exposure: 8.6 years); 3. Kishi et al.(1992a): gestational days 7–21, developmental study (in utero exposure of the pups via maternal inhalation exposure); 4. Kishi et al. (1992b): gestational days 7–21, developmental study (in utero exposure of the pups via maternal inhalation exposure).

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Toxicological reference values for tetrachloroethylene (CAS RN 127-18-4)
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:
Study 6
LOAEL = 156 mg/m3
LOAELADJ = 56 mg/m3
Study 3
LOAEL = 42 mg/m3
LOAELADJ = 15 mg/m3

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
(UFH = 10, UFL = 10, UFDB = 10)

100
(UFH = 10, UFL = 10)
Concentration (µg/m3) n/a n/a 40 360 250

40
(rounded average of 15 and 56)

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.
UFDB for lack of neurological, developmental, and immunological studies.

LOAELADJ = LOAEL x 40 hr/week / 168 hr week
Footnote 1

The ATSDR and US EPA non-cancer TRVs were retained as the IARL: The US EPA cancer TRV was selected as the IARL as the assessment used data that were not available at the time of the OEHHA assessment.

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Footnote 2

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (1993d).

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Footnote 3

The RIVM assessment was published under the authorship of Baars et al. (2001).

Return to footnote 3 referrer

Footnote 4

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2015).

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Footnote 5

1. NTP (1986a): 2-year inhalation study; 2. JISA (1993): 2-year inhalation study; 3. Cavalleri et al. (1994): occupational neurobehavioural testing; 4. Gobba et al. (1998): occupational neurobehavioural testing; 5. Mutti et al. (1992) : occupational exposure study; 6. Echeverria et al. (1995): occupational neurobehavioural testing.

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Toxicological reference values for toluene diisocyanate (mixed isomers) (CAS RN 26471-62-5) (updated 2023)
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
NOAELADJ = 0.002 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.

Footnote 1

The OEHHA non-cancer TRV was retained as the IARL.

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Footnote 2

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA reports (2011, 2015, 2016).

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Footnote 3

AEL: adverse effect level.

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Footnote 4

1. NTP (1986c): 106-week ingestion study (gavage); 2. Clark et al. (1998): 5-year occupational study; 3. Diem et al. (1982): 5-year occupational study.

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Cancer toxicological reference values for trichloroethylene (CAS RN 79-01-6) (added 2023)
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.
IUR = 0.05/TC05

Linearized multistage modelling; PBPK modelling; geometric mean of IUR for 4 studies.
*IUR derived in 1990.

IUR= 0.01/ LEC0.1
IUR derived for kidney tumours, then applied a factor of 4 to account for additional risk from non-Hodgkin's lymphoma and liver tumours

*IUR derived in 2000.

DWG, Drinking Water Guidelines, PSL, Priority Substances List

Footnote 1

The Health Canada assessment was published under the authorship of Environment Canada and Health Canada (1993e).

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Footnote 2

The US EPA TRV was retained as the IARL.

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Footnote 3

US EPA - IRIS (2011) IUR was also adopted by Health Canada (CSD) and US EPA (TSCA).

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Footnote 4

1. Maltoni et al. (1986): 2-year inhalation study. 2. Bell et al. (1978): 2-year inhalation study; 3. Henschler et al. (1980): 78-week inhalation study; 4. Fukuda et al. (1983): 2-year inhalation study; 5. Charbotel et al. (2006): occupational study; 6. Raaschou-Nielsen et al. (2003): occupational study; 7. Maltoni et al. (1988): 104-week inhalation study.

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Non-cancer toxicological reference values for trichloroethylene (CAS RN 79-01-6) (added 2023)
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:
LOAEL = 0.35 mg/ kg/d
HEC99-LOAEL = 0.0332 ppm (0.19 mg/m3)

Rat:
BMDL0.1: 0.0142mg TCE oxidized/kg bw/ 3/4day
HEC99-BMDL01 = 0.0037 ppm (0.019 mg/m3)

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)
Rat: 10 (UFA= 3; UFH= 3)

Concentration (µg/m3) 3.2 5 600 200

Mouse: 1.9
Rat: 2.1
Overall: 2

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).
Air concentration = TDI x allocation factor for air (0.8) x body weight (70kg) / inhalation rate (15 m3/d)

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

Footnote 1

The RIVM assessment was published under the authorship of Baars et al. (2001).

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Footnote 2

The US EPA TRV was retained as the IARL.

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Footnote 3

The US EPA (IRIS) (2011) value was adopted by ATSDR (2019) and Health Canada (CSD) (2021).

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Footnote 4

Refers to the actual date of assessment. Toxicological reference value information was summarized from OEHHA report (2014b).

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Footnote 5

7. Maltoni et al. (1988): 104-week inhalation study; 8. Keil et al. (2009): 27-week drinking water study. 9. Johnson et al. (2003): gestational drinking water study; 10. Vandervort and Polnkoff (1973): occupational study; 11. Dawson et al. (1993): gestational drinking water study. 12. Kjellstrand et al. (1983): 30-day continuous inhalation study.

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Toxicological reference values for vinyl chloride (CAS RN 75-01-4) (added 2023)
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:
8.8 x 10-6

For continuous lifetime exposure through adulthood:
4.4 x 10-6

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.
Footnote 1

The US EPA cancer TRV was retained as the IARL: The mode of action for tumour development is dependent on liver metabolism; therefore, the OEHHA cancer TRV based on lung tumours was not considered appropriate, and the US EPA cancer TRV based on liver tumours was selected for the IARL.

Return to footnote 1 referrer

Footnote 2

ATDSR developed an intermediate MRL, but not a chronic MRL.

Return to footnote 2 referrer

Footnote 3

UFA Interspecies, UFH Intraspecies, UFL LOAEL to NOAEL.

Return to footnote 3 referrer

Footnote 4

1. Maltoni et al. (1981, 1984b): 1-year inhalation study; 2. Til et al. (1983): Lifetime dietary study; 3. Thornton et al. (2002): 19-week inhalation study; 4. Hong et al. (1981): 28-week (mice) and 52-week (rat) inhalation study; 5. Drew et al. (1983): 2-year inhalation study; 6. Nicholson (et al). 1984; occupational study; 7. Equitable Environmental Health (1978): occupational study.

Return to footnote 4 referrer

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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.

Return to footnote 1 referrer

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