Developmental and reproductive

Another section of the EPA, the Office of Prevention, Pesticides, and Toxic Substances (OPPT), has recently updated and harmonized its testing guidelines for evaluating the developmental and reproductive effects of pesticides and industrial chemicals to include an assessment of endocrine disrupting properties. These guidelines will be used in future testing of pesticides under both the Toxic Substances Control Act (TSCA) and the Federal Insecticide, Fungicide and Rodenticide Act (FIFRA). 

Toxicologists tend to focus their attention primarily on c.xtrapolations from cancer bioassays. However, tlicrc is also a need to evaluate the risks of lower doses to see how they affect the various organs and systems in the body. Many scientific papers focused on tlic use of a safety factor or uncertainty factor approach, since all adverse effects other than cancer and mutation-based dcvclopmcnUil effects are believed to have a tlu cshold i.e., a dose below which no adverse effect should occur. Several researchers have discussed various approaches to setting acceptable daily intakes or exposure limits for developmental and reproductive toxicants. It is Uiought Uiat an acceptable limit of exposure could be determined using cancer models, but today tliey arc considered inappropriate because of tlircsholds. ... 

No developmental and reproductive toxicity data on humans concerning aniline were identified in the available literature. 

No studies addressing developmental or reproductive effects following acute inhalation exposure to aniline were located. However, because effects on development and reproduction arise after systemic uptake, oral administration of aniline can be considered for evaluating potential developmental and reproductive toxicity. Aniline (administered as aniline hydrochloride) readily crosses the placental barrier in rodents (Price et al. 1985). 

The only available data regarding developmental and reproductive effects of dimethylhydrazine involved parenteral administration and, therefore, are of questionable relevance for AEGL derivation. The data are included, however, to provide insight relative to dimethylhydrazine exposure. 

Homung, M.W., L. Miller, B. Goodman, M.J. Melancon, and R.E. Peterson. 1998. Lack of developmental and reproductive toxicity of 2,3,3, 4,4 -pentachlorobiphenyl (PCB 105) in ring-necked pheasants. Arch. Environ. Contam. Toxicol. 35 646-653. 

Another consensus recommendation was that, when possible, methods to assess DIT should be included in existing developmental and reproductive toxicology protocols.1719,30 The feasibility of this approach has been previously demonstrated in studies described by a number of investigators.34 35 36 While it could be argued that DIT methods could also be integrated into the EPA Developmental Neurotoxicity Protocol (OPPTS 870-630037) the consensus was that this approach would not be technically feasible due to the large number of animals already required to conduct that study.7,19,30... 

Developmental and reproductive studies regarding acute human exposure to phosgene were not available. 

Data adequacy The key study was well designed, conducted, and documented used 20 human subjects and utilized a range of concentrations and exposure durations. Occupational exposures support the 8-h AEGL value. The mechanism of headache induction (vasodilation) is well understood and occurs following therapeutic administration of nitrate esters to humans. Animal studies utilized several mammalian species and addressed metabolism, neurotoxicity, developmental and reproductive toxicity, and potential carcinogenicity. ... 

Developmental and Reproductive Toxicity. This was an area in which there was considerable international disagreement and the area in which ICH has promulgated the most technically detailed guidelines (S5A and S5B). Some of the major changes include ... 

This chapter briefly describes the current standard study designs and then focuses on current issues in developmental and reproductive toxicity testing. 

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