Guidelines for Developmental Toxicity Risk Assessment

By Environmental Protection Agency

Book Id: WPLBN0000126490
Format Type: PDF eBook
File Size: 0.2 MB
Reproduction Date: 2007

Title:	Guidelines for Developmental Toxicity Risk Assessment
Author:	Environmental Protection Agency
Volume:
Language:	English
Subject:	Ecology, Natural resource issues, Environemtal protection
Collections:	Environmental Awareness Library Collection
Historic Publication Date:
Publisher:	United States Environmental Protection Agency


Citation APA MLA Chicago Agency, E. P. (n.d.). Guidelines for Developmental Toxicity Risk Assessment. Retrieved from http://www.gutenberg.us/

Description
Excerpt: SUMMARY: The U.S. Environmental Protection Agency (EPA) is today issuing final amended guidelines for assessing the risks for developmental toxicity from exposure to environmental agents. As background information for this guidance, this notice describes the scientific basis for concern about exposure to agents that cause developmental toxicity, outlines the general process for assessing potential risk to humans because of environmental contaminants, summarizes the history of these guidelines, and addresses public and Science Advisory Board comments on the 1989 “Proposed Amendments to the Guidelines for the Health Assessment of Suspect Developmental Toxicants” [54 FR 9386-9403]. These guidelines, which have been renamed “Guidelines for Developmental Toxicity Risk Assessment” (hereafter “Guidelines”), outline principles and methods for evaluating data from animal and human studies, exposure data, and other information to characterize risk to human development, growth, survival, and function because of exposure prior to conception, prenatally, or to infants and children. These Guidelines amend and replace EPA’s 1986 “Guidelines for the Health Assessment of Suspect Developmental Toxicants” [51 FR 34028-34040] by adding new guidance on the relationship between maternal and developmental toxicity, characterization of the health-related database for developmental toxicity risk assessment, use of the reference dose or reference concentration for developmental toxicity (RfDDT or RfCDT), and use of the benchmark dose approach. In addition, the Guidelines were reorganized to combine hazard identification and dose-response evaluation since these are usually done together in assessing risk for human health effects other than cancer.

Table of Contents
CONTENTS Lists of Tables and Figures . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Federal Register Preamble . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vi Part A: Guidelines for Developmental Toxicity Risk Assessment 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 2. Definitions and Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 3. Hazard Identification/Dose-Response Evaluation of Agents That Cause Developmental Toxicit y 4 3.1. Developmental Toxicity Studies: Endpoints and Their Interpretation . . . . . . . . . . . . . . . . . . 5 3.1.1. Laboratory Animal Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 3.1.1.1 Endpoints of Maternal Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 3.1.1.2. Endpoints of Developmental Toxicity: Altered Survival, Growth, and Morphological Development . . . . . . . . . . . . . . . . . . . . . . . . 9 3.1.1.3. Endpoints of Developmental Toxicity: Functional Deficits . . . . . . . . . . . 13 3.1.1.4. Overall Evaluation of Maternal and Developmental Toxicity . . . . . . . . . . 17 3.1.1.5. Short-Term Testing in Developmental Toxicity . . . . . . . . . . . . . . . . . . . 18 3.1.1.6. Statistical Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 3.1.2. Human Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 21 3.1.2.1. Epidemiologic Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.1.2.2. Examination of Clusters or Case Reports/Series . . . . . . . . . . . . . . . . . . 31 3.1.3. Other Considerations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3.1.3.1. Pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 31 3.1.3.2. Comparisons of Molecular Structure . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 3.2. Dose-Response Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32 3.3. Characterization of the Health-Related Database . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37 3.4. Determination of the Reference Dose (RfDDT) or Reference Concentration (RfCDT) for Developmental Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40 3.5. Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42