Biomedical subjects

J C Lamb

Publications and source records attributed to J C Lamb.

76 records · Page 5Linked to original sources

PubMedDate not supplied

Chemical testing strategies for predicting health hazards to children.

The United States Environmental Protection Agency has proposed the development of a Children's Health Test Program under the Toxic Substances Control Act. The Environmental Protection Agency's proposal for the children's health test battery has 12 different assays including general toxicity, genotoxicity, carcinogenicity, neurotoxicity, and developmental and reproductive toxicity. The current Environmental Protection Agency testing proposal is an "all or nothing" test battery. An alternative and preferable approach would be to use a science-based, tiered testing scheme. It is proposed that the Screening Information Dataset program, currently used by the Organization for Economic Co-operation and Development (OECD) for the Screening Information Dataset-High Production Volume test battery, or equivalent, be considered for the first step. Step 1 would include acute and repeat dose toxicity testing, developmental toxicity testing (first species OECD 414 or OECD 422), reproductive toxicity screening (OECD 415 or 422), and genetic toxicity testing. For this step, the rat would be the initial and only species tested unless the mouse was used for in vivo genetic toxicity. Step 2 of the proposed children's health test battery would include developmental testing (second species OECD 414) or special mode of action studies performed for those chemicals that proved to be developmental toxicants in Step 1. Those chemicals that tested positive as reproductive toxicants in Step 1 would be tested in a two-generation reproduction study (OECD 416) or a special mode of action study. Steps 1 and 2 provide information on whether oncogenicity or developmental neurotoxicity testing is useful. Step 3 would include chronic toxicity/oncogenicity testing for those chemicals that tested positive for genetic toxicity in Step 1, and positive for developmental concerns in Step 2. In this step, chemicals would also be tested for developmental neurotoxicity if they showed evidence of neuropathy, behavioral effects, or neurotoxic potential in earlier studies. This stepwise approach would conserve resources and answer scientific questions in a logical, orderly, timely, and cost-effective manner.

Animals↗

PubMedDate not supplied

Toxicity of chlorinated phenoxy acids in combination with 2,3,7,8-tetrachlorodibenzo-p-dioxin in C57BL/6 male mice.

Male C57BL/6 mice were given feed containing various concentrations of 2,4,-dichlorophenoxyacetic acid (2,4-D),2,4,5-trichlorophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to provide daily doses of approximately 40 mg/kg 2,4,-D, 40 mg/kg 2,4,5-T, and 2.4 micrograms/kg TCDD (group II): 40 mg/kg 2,3-D, 40 mg/kg 2,4,5-T, and 0.16 micrograms/kg TCDD (group III); and 20 mg/kg 2,4-D, 20 mg/kg 2,4,5-T, and 1.2 micrograms/kg TCDD (group IV). The chemical mixtures were chosen to approximate the concentrations of the components of Herbicide Orange. Controls (group I) were given a diet with only the corn oil vehicle added to the feed. In the treated animals, liver enlargements, hepatocellular toxicity, and reduced thymus size were found an body weight gain was significantly less than that of the control animals. Significant of complete recovery from liver and thymus toxicity was observed when the mice were returned to a control diet. The thymic toxicity and hepatotoxicity seemed to be related to TCDD levels, while the decrease in body weight gain was more closely associated with phenoxy acid concentrations. All effects attributed to the mixture were elicited by individual compounds in the mixture in previous studies.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMedDate not supplied

Male fertility, sister chromatid exchange, and germ cell toxicity following exposure to mixtures of chlorinated phenoxy acids containing 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Fertility and sperm number, motility, and morphology were analyzed in male C57BL/6 mice exposed to various mixtures of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlor-ophenoxyacetic acid (2,4,5-T), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the diet for 8 wk. Somatic cell (bone marrow) sister chromatid exchange frequencies were also evaluated in mice injected with similar chemical mixtures. The concentration of the test chemicals was such that the average daily feeding dose in the three mixtures or control was 40 mg/kg 2, 4-D, 40 mg/kg 2,4,5-T, and 2.4 micrograms/kg TCDD; 40 mg/kg 2,4-D, 40 mg/kg 2,4,5-T and 0.16 microgram/kg TCDD; 20 mg/kg 2, 4-D, 20 mg/kg 2,4,5-T, and 1.2 micrograms/kg TCDD; or no chemical added (control). No significant dose-related effects were observed in the treated mice compared to the control group.

2,4,5-Trichlorophenoxyacetic Acid↗

PubMedDate not supplied

Development and viability of offspring of male mice treated with chlorinated phenoxy acids and 2,3,7,8-tetrachlorodibenzo-p-dioxin.

Male C57BL/6 mice were given feed containing various concentrations of 2,4-dichlorophenoxyacetic acid (2,4-D), 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) such that their diets contained daily doses of approximately 40 mg/kg 2,4,-D, 40 mg/kg 2,4,5-T, and 2.4 micrograms/kg TCDD (group II); 40 mg/kg 2,4-D, 40 mg/kg 2,4,5-T, and 0.16 microgram/kg TCDD (group III); or 20 mg/kg 2,4-D, 20 mg/kg 2,4,5-T, and 1.2 micrograms/kg TCDD (group IV). Controls (group I) were given a diet with only the corn oil vehicle added to the feed. At the conclusion of an 8-wk dosing period, treated males cohabited with untreated virgin C57BL/6 female mice. Females were randomly assigned either to undergo teratological examination at 18 d of gestation, when the fetuses were examined for external, visceral, and skeletal malformations, or to be segregated and allowed to deliver their pups. Live and dead offspring and birth weight were recorded and viability was monitored until postnatal d 21. In both cases, development and survival of offspring in the test groups, whose sire had been treated with the mixture of phenoxy acids and TCDD, were not significantly different from those in the control group, whose sire had received untreated feed.

2,4,5-Trichlorophenoxyacetic Acid↗