US-EPA Test Guidelines

OPPT has developed a series of test guidelines called the Harmonized Test Guidehnes. Eor health effects, the relevant guidelines are Series 870, Health Effects Test Guidelines. These guidelines are addressed in more detail in Chapter 4. The adopted test guidelines are listed in Table 2.7 and the draft test guidelines are listed in Table 2.8. 

US-EPA (OPPT) Harmonized Test Guidelines, Series 870, Health Effects Test Guidelines, Final Guidelines 

3050 Repeated dose 28-day oral toxicity smdy in rodents (July 20(X)) 

3550 Reproduction/developmental toxicity screening test (July 2000) 

3650 Combined repeated dose toxicity smdy with the reproduction/developmental toxicity screening test (July 2000) 870.3700 Prenatal developmental toxicity smdy (August 1998) 

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In the US-EPA test guideline for acute dermal irritation (OPPTS 870.2500), the following definitions are provided ... 

In the US-EPA test guidelines for carcinogenicity and combined chronic toxicity/carcinogeni-city (OPPTS 870.4200 and OPPTS 870.4300, respectively), the following definition is provided Carcinogenicity is the development of neoplastic lesions as a result of the repeated daily exposure of experimental animals to a chemical by the oral, dermal, or inhalation routes of exposure. ... 

US EPA, Residue Chemistry Test Guideline. OPPTS 860.1340 Residue Analytical Chemistry, US Environmental Protection Agency, Washington, DC (1996). Also available on the World Wide Web http //fedhss.access.gpo.gov. 

US EPA, Occupational and Residential Exposure Test Guidelines, OPPTS 875.2000, Background for Postapplication Exposure Monitoring Test Guidelines, Environmental Protection Agency, Washington, DC, p. 4 (1996). 

A Comparison with Vertebrate Testing Systems (US EPA Subdivision M Assessment Guidelines) with Biomarkers of ImmunotoxicityThat Have Been Developed and Applied to Different Invertebrate Species... 

The harmonized test guidelines have been developed for use in the testing of pesticides and toxic substances, and the development of test data that must be submitted to the US-EPA for review under Federal regulations. The OPPT guidelines are based on the OECD test guidelines (Section 2.2.6) however, minor deviations may occur. The guidelines are available for download at the OPPT Web site (US-EPA 2006d). 

US-EPA. 2006c. The United States Environmental Protection Agency Toxic Substances Control Act New Chemicals Program website, www.epa.gov/opptintr/newchems US-EPA. 2006d. United States Environmental Protection Agency Test guidelines, http //www.epa. 

The OECD, US-EPA, and EU have adopted in vivo test guidelines for the performance of toxicokinetic studies. The various guidelines are shown in Table 4.1 and are described further in the text below. 

Test guidelines for acute toxicity testing have been adopted by the OECD, US-EPA, and EU, see Table 4.6. 

There are three US-EPA OPPTS Test Guidelines for acute toxicity testing. OPPTS 870.1100 is similar to OECD TG 425 (Acute Oral Toxicity Up-and-Down Procedure). OPPTS 870.1200 and OPPTS 870.1300 are similar to OECD TG 402 and 403, respectively. 

The standard repeated dose toxicity guidehne studies include a number of parameters relevant for the evaluation of a substance s immunotoxic potential. While some information on potential immunotoxic effects may be obtained from the evaluation of hematology, lymphoid organ weights, and histopathology in these studies, there are data which demonstrate that these endpoints alone are not sufficient to predict immunotoxicity. In addition to these standard studies, the US-EPA has developed a specific test guideline for immunotoxicity testing in rodents (OPPTS 870.7800). This... 

The US-EPA has adopted four different test guidelines for neurotoxicity ... 

The immunotoxicity study will provide information on suppression of the immune system, which might occur as a result of repeated exposure to a test chemical. The protocol for the US-EPA OPPTS test guideline is intended to be used along with data from routine toxicity testing, to provide more accurate information on risk to the immune system. See also Section 4.7.6. 

The US-EPA OPPTS test guideline on immunotoxicity (OPPTS 870.7800) provides the following definition Immunotoxicity refers to the ability of a test substance to suppress immune responses that could enhance the risk of infectious or neoplastic disease, or to induce inappropriate stimulation of the immune system, thus contributing to allergic or autoimmune disease. ... 

The series of Risk Assessment Guidelines includes a guideline for neurotoxicity risk assessment (US-EPA 1998). This Guideline sets forth principles and procedures to guide US-EPA scientists in evaluating environmental contaminants that may pose neurotoxic risks, and inform US-EPA decision-makers and the public about these procedures. The Guideline includes a discussion of general dehnitions and issues, an overview of test methods, and the interpretation of data within the U.S. framework for risk assessment. 

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