DfE Reproductive and Developmental Toxicity

3.6 REPRODUCTIVE AND DEVELOPMENTAL TOXICITY

Criteria

Chemicals that are considered reproductive or developmental toxicants under GHS criteria [64] (see guidance values in Table 7) shall not pass the Criteria. 

Table 7 – GHS Guidance Values

Additionally, a chemical cannot be associated with the following authoritative lists:

Table 8 – Reproductive and Developmental Toxicity Authoritative Lists

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. 

All relevant data and information used to place a chemical on the following lists will be considered when reviewing a listed chemical against the reproductive and developmental toxicity criteria.

1. 1. Substances prioritized for testing for endocrine disruption by the European Commission as Category 1 or 2 [17, 18]
2. 2. Substances prioritized for testing for endocrine disruption by the US EPA Endocrine Disruptor Screening Program [4]
3. 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 Reproductive Toxicity [19].

 

Test Methods for GHS Review

 

Fertility test methods, preferred

 

– OECD Test Guideline 415: One-Generation Reproduction Toxicity Study [65] and

– OECD Test Guideline 416: Two-Generation Reproduction Toxicity Study [66].

 

Fertility test methods, acceptable

 

The following test methods may be used to identify reproductive toxicity, per GHS [64]:

 

– OPPTS Harmonized Guideline 870.3800: Reproduction and fertility effects [67];

– OECD Test Guideline 421: Reproduction/Developmental Toxicity Screening Test [68];

– OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test [61];

– OPPTS Harmonized Guideline 870.3550: Reproduction/developmental toxicity screening test [69]

– OPPTS Harmonized Guideline 870.3650: Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test [70].

 

Developmental toxicity test methods, preferred

 

– OECD Test Guideline 414: Prenatal Developmental Toxicity Study [71]

 

Developmental toxicity test methods, acceptable

 

The following test methods may be used to identify developmental toxicity, per GHS [64]:

 

– OPPTS Harmonized Guideline 870.3800: Reproduction and fertility effects [67];

– OECD Test Guideline 421: Reproduction/Developmental Toxicity Screening Test [68];

– OECD Test Guideline 422: Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test [61];

– OPPTS Harmonized Guideline 870.3550: Reproduction/developmental toxicity screening test [69];

– OPPTS Harmonized Guideline 870.3650: Combined repeated dose toxicity study with the reproduction/developmental toxicity screening test [70]; and

 

Data Interpretation

 

The following sources should be consulted for additional information:

 

– GHS Ch 3.7 Reproductive Toxicity [64]

– Part A, Section 3, Hazard Characterization in Guidelines for Reproductive Toxicity Risk Assessment (EPA 1998), http://www.epa.gov/ncea/raf/pdfs/repro51.pdf [72].

– Part A, Section 3, Hazard Characterization in Guidelines for Developmental Toxicity Risk Assessment (EPA 1991), http://www.epa.gov/NCEA/raf/pdfs/devtox.pdf [73].

– 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].