DfE Repeated Dose Toxicity

3.5 REPEATED DOSE TOXICITY

Criteria

Chemicals that are considered repeated dose (systemic) toxicants under GHS [49] (see GHS guidance values in Table 6) shall not pass the Criteria. Repeated dose toxicity is called Specific Target Organ Toxicity Repeated Exposure in GHS.

Table 6 – GHS Guidance Values

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 repeated dose 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 Cancer [19].

 

Preferred Test Methods

 

– OECD Test Guideline 408: Repeated Dose 90-Day Oral Toxicity Study in Rodents [50]

– OECD Test Guideline 409: Repeated Dose 90-Day Oral Toxicity Study in Non-Rodents [51]

– OECD Test Guideline 411: Subchronic Dermal Toxicity: 90-day Study [52]

– OECD Test Guideline 413: Subchronic Inhalation Toxicity: 90-day Study [53]

– OPPTS Harmonized Guideline 870.3100: 90-Day oral toxicity in rodents [54]

– OPPTS Harmonized Guideline 870.3150: 90-Day oral toxicity in nonrodents [55]

– OPPTS Harmonized Guideline 870.3250: 90-Day dermal toxicity [56]

– OPPTS Harmonized Guideline 870.3465: 90-Day inhalation toxicity [57]

 

Acceptable Test Methods

 

– OECD Test Guideline 412: Repeated Dose Inhalation Toxicity: 28-day Study [58]

– OECD Test Guideline 410: Repeated Dose Dermal Toxicity: 28-day Study [59]

– OECD Test Guidelines 407: Repeated Dose 28-day Oral Toxicity Study in Rodents [60]

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

– OPPTS Harmonized Guideline 870.3050: Repeated dose 28-day oral toxicity study in rodents [62]

– OPPTS Harmonized Guideline 870.3200: 28-Day dermal toxicity [63]

 

Data Interpretation

 

– GHS Ch 3.9 Specific Target Organ Toxicity Repeated Exposure [49],

– 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].