IP03 Avian Endocrine Test Protocols
B113 & B114
1:20 PM - 4:40 PM, Monday
(IP023) Endocrine Endpoints Evaluated During an OECD One Generation Avian Reproduction Study.
Brewer, L1, Stafford, J.1, Ash, K.2, Mihaich, E.3, Becker, R.4, Famula, T5, Millam, J.5, 1 Springborn Smithers Laboratories, Snow Camp, NC, USA2 California State University, Sacramento, CA, USA3 E. M. Mihaich Consulting, Durham, NC, USA4 American Chemistry Council, Arlington, VA, USA5 University of California Davis CA, Davis, CA, USA
ABSTRACT- Four endocrine endpoints were added to a single-generation avian reproduction study conducted according to OECD draft guidelines, which called for exposing Japanese quail to a test substance after two weeks of egg production. The objective was to evaluate selected endocrine endpoints for their potential to identify an endocrine-active compound during in a one-generation study. The added endpoints were: 1. fecal steroid hormone analysis; 2. egg yolk estrogen level; 3. oviduct growth and development, including histological analysis, in 14-day hatchlings exposed to the test substance post-hatch; and 4. circulating estradiol and testosterone levels. The test substance, methoxycholor was mixed into feed at 0, 5, 20, 80 and 320 ppm. Feed was fed for 6 weeks following the first two weeks of egg production. Excreted testosterone and estrogen levels seemed unaffected by the methoxychlor. Egg yolk estradiol was highly variable in all groups and was not significantly different among groups. Chick oviduct weight increased, but not as much as in those of positive control birds exposed to a range of estradiol benzoate doses, including 1, 10 or 100 nmol/g body weight via daily gavage in 1-14 day hatchling, and the increase did not show a clear dose-response relationship. Histological analysis showed that the type of oviduct growth induced by methoxychlor differed from that induced by estradiol; it was less robust and methoxychlor-treated quail showed a much greater incidence of detached epithelia. Body weight of methoxychlor-exposed chicks increased at all exposure levels except 300 ppm, at which, chick body weights were reduced. Mean blood estradiol and testosterone levels were not significantly different at three time points: acclimation, lights up and test termination. Monitoring excreted hormone levels and 14-day oviduct and body weights in combination appear to be the most sensitive endpoints in this study. However, the data indicate that methoxychlor is either very weakly estrogenic or has indirect effects on the endocrine system. These endpoints should be tested with a compound that produces stronger estrogenic effects before final conclusions are made about their value as detectors of endocrine effects during an avian reproduction study.
Key words: endocrine endpoints, methoxychlor, avian reproduction study, estrogenic