Results of the negative control chemical allyl alcohol in the 15-day intact adult male rat screening assay for endocrine activity.
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.
O'Connor
John C
JC
DuPont Haskell Global Centers for Human Health and Environmental Sciences, Newark, DE 19714, USA. john.c.oconnor@usa.dupont.com
Marty
M Sue
MS
Becker
Richard A
RA
Snajdr
Suzanne
S
Kaplan
A Michael
AM
D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight / Q000187:drug effects; D003940:Diagnostic Techniques, Endocrine; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000592:standards*; D052244:Endocrine Disruptors / Q000633:toxicity*; D005260:Female; D006728:Hormones / Q000032:analysis / Q000097:blood; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008297:Male; D009929:Organ Size / Q000187:drug effects; D020005:Propanols / Q000494:pharmacology* / Q000592:standards / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012015:Reference Standards; D013737:Testis / Q000033:anatomy & histology / Q000187:drug effects; D013961:Thyroid Gland / Q000033:anatomy & histology / Q000187:drug effects
D052244:Endocrine Disruptors; D006728:Hormones; D020005:Propanols; C006463:allyl alcohol