3.2 CARCINOGENICITY
Criteria
Data Requirements
Test Methods
CriteriaChemicals considered carcinogens according to the authoritative lists below (see Table 3) shall not pass the Criteria. Chemicals not on those authoritative lists, but that are known or presumed human carcinogens (Category 1), or suspected human carcinogens (Category 2) under GHS [15], shall not pass the Criteria.
Table 3 – Authoritative Lists and GHS Criteria
| Authoritative Body | Does not pass DfE Criteria |
| National Toxicology Program (NTP) | Known to be Human Carcinogen Reasonably Anticipated to be Human Carcinogen |
| U.S. Environmental Protection Agency (EPA) | (2005/1999) “Carcinogenic to humans”, “Likely to be carcinogenic to humans”, or “Suggestive evidence of carcinogenic potential”4 (1996) “Known/Likely” (1986) “Group A – Human Carcinogen”, “Group B – Probable human carcinogen,” or “Group C – Possible human carcinogen”4 |
| International Agency for Research on Cancer (IARC) | Group 1 – carcinogenic to humans Group 2A – probably carcinogenic to humans Group 2B – possibly carcinogenic to humans |
| EU CMR List [16] | Category 1 – Known Category 2 – Should be considered carcinogenic to humans Category 3 – Possible carcinogenic effects |
| EU Risk Phrases [16] | R45: “May cause cancer” R49: “May cause cancer by inhalation” R40: “Limited evidence of a carcinogenic effect” And all combination risk phrases containing one or more of the above. |
| Globally Harmonized System (GHS) [15] | Category 1A – Known to have carcinogenic potential for humans Category 1B – Presumed to have carcinogenic potential for humans Category 2 – Suspected human carcinogens |
Data Requirements
All available data, measured and/or estimated, for the chemical and/or a suitable analog will be reviewed against the criteria using a weight-of-evidence approach.
Chemicals that appear on one of the lists of chemicals of concern below will require Supplemental Review.
- 1. Substances prioritized for testing for endocrine disruption by the European Commission as Category 1 or 2 [17, 18],
- 2. Substances prioritized for testing for endocrine disruption by the US EPA Endocrine Disruptor Screening Program [4],
- 3. Substances listed on the State of California Environmental Protection Agency, Office of Environmental Health Hazard Assessment (OEHHA) California Proposition 65 (Safe Drinking Water and Toxic Enforcement Act Of 1986) as Known to the State to Cause Cancer [19].
Test Methods for GHS Review
– OECD Test Guideline 451: Carcinogenicity Studies [20];
– OECD Test Guideline 453: Combined Chronic Toxicity/Carcinogenicity Studies [21];
– OPPTS Harmonized Guidelines 870.4200: Carcinogenicity [22];
– OPPTS Harmonized Guidelines 870.4300: Combined chronic toxicity/carcinogenicity [23] and
– NTP 2 Year Study Protocol: “Specifications for the conduct of studies to evaluate the toxic and carcinogenic potential of chemical, biological and physical agents in laboratory animals for the National Toxicology Program” [24].
Data Interpretation
– EU Dangerous Substances Directive, http://ecb.jrc.ec.europa.eu/documentation/. To access the list of substances carrying Risk Phrases, click on “CLASSIFICATION-LABELLING”, then “DIRECTIVE 67-548-EEC”, then “ANNEX I OF DIRECTIVE 67-548-EEC”, and then either of the files listed as: “Annex I of Directive 67548EEC”. [25];
– EU Dangerous Preparations Directive Article 6 and Annex II (1999/45/EC and subsequent updates/amendments) [26-28];
– GHS Ch 3.6 Carcinogenicity [15];
– Section 2, Hazard Assessment in Guidelines for Carcinogen Risk Assessment (Risk Assessment Forum) (EPA 2005), http://oaspub.epa.gov/eims/eimscomm.getfile?p_download_id=439797 [29] and
– The following link can be used to identify substances prioritized for testing for endocrine disruption by the European Commission: http://ec.europa.eu/environment/endocrine/strategy/substances_en.htm#priority_list. To download the list of substances, see the zipped file under the heading “Priority List” [17].
– The following report describes the process used to develop the endocrine disrupters priority list: http://ec.europa.eu/environment/endocrine/documents/final_report_2007.pdf [18].
– EPA Endocrine Disruptors Screening Program, available at: http://www.epa.gov/endo/ [4].
– Supplemental Guidance for Assessing Susceptibility from Early-Life Exposure to Carcinogens, available at: http://cfpub.epa.gov/ncea/CFM/recordisplay.cfm?deid=160003 [30].
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