Results of the negative control chemical allyl alcohol in the 15-day intact adult male rat screening assay for endocrine activity.
Birth Defects Res B Dev Reprod Toxicol
; 83(2): 117-22, 2008 Apr.
Article
em En
| MEDLINE
| ID: mdl-18383315
ABSTRACT
Development, standardization, and validation of methods to assess the potential of chemicals to disrupt hormonal homeostasis have been the focus of considerable research efforts over the past 10 years. As part of our validation effort, we evaluated the specificity of the 15-day intact adult male rat assay, using a negative control chemical, allyl alcohol, a known hepatotoxicant that was not expected to induce endocrine effects. Male rats were dosed for 15 days via oral gavage with 0, 10, 30, 40, or 50 mg/kg/day allyl alcohol. The endpoints evaluated included final body and organ weights, serum hormone concentrations, and a limited histopathology assessment. No mortality or adverse clinical signs were observed. Mean final body weight for rats in the 50-mg/kg/day dose group was decreased to 90% of control. Mean relative liver weights were increased at 40 and 50 mg/kg/day (115% and 117% of control, respectively). Serum testosterone and DHT concentrations were statistically significantly decreased at 50 mg/kg/day (72% of control). Serum prolactin concentrations were statistically significantly decreased at 40 mg/kg/day (58% of control), but not at 50 mg/kg/day. There were no effects on the other endpoints evaluated. Consistent with previous guidance for interpreting the 15-day intact adult male rat assay, histological and weight changes of target organs were given a higher weight-of-evidence than changes in serum hormone concentrations alone. Therefore, with only minimal changes in serum hormone concentrations and no effects on organ weights or microscopic alterations, the results of allyl alcohol in the 15-day intact adult male rat assay were considered negative and consistent with the predicted results.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Propanóis
/
Técnicas de Diagnóstico Endócrino
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Avaliação Pré-Clínica de Medicamentos
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Disruptores Endócrinos
Tipo de estudo:
Diagnostic_studies
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Guideline
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Prognostic_studies
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Screening_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article