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This study determined the effects of feed restriction (FR) during in utero and postnatal life on standard reproductive toxicity and developmental immunotoxicity end points. Groups of 26 time-mated CD rats were fed various amounts of Purina 5002 diet from gestation day 7 through lactation. Control rats were fed once per day in amounts based on historical(More)
The Endocrine Disrupter Screening and Testing Advisory Committee has recommended the female pubertal onset assay as a Tier I test to detect potential endocrine-disrupting chemicals (EDs). We evaluated this assay's ability to detect EDs acting through various mechanisms. In two similar experiments, weanling female rats were dosed for 20 days by gavage with(More)
An extensive database on the toxicity and modes of action of ethylene glycol (EG) has been developed over the past several decades. Although renal toxicity has long been recognized as a potential outcome, in recent years developmental toxicity, an effect observed only in rats and mice, has become the subject of extensive research and regulatory reviews to(More)
The extended one-generation reproduction toxicity study (OECD 443, adopted 28-July-2011) produces more information with fewer animals than the two-generation study (OECD 416), by including F1 neurotoxicity and immunotoxicity assessments, and omitting an F2 generation if there are no relevant F1 findings. This saves >1000 animals per compound. Feasibility(More)
Delayed (or incomplete) ossification of developing fetal bones and wavy ribs are some of the most common skeletal variations encountered in regulatory guideline developmental toxicity studies. Although they tend to be regarded as minor effects, they can be quite sensitive and consequently may influence the study lowest-observed-adverse-effect levels(More)
The kinetics of orally administered ethylene glycol (EG) and its major metabolites, glycolic acid (GA) and oxalic acid (OX), in pregnant (P; gestation day 10 at dosing, GD 10) rats were compared across doses, and between pregnant and nonpregnant (NP) rats. Groups of 4 jugular vein-cannulated female rats were administered 10 (P and NP), 150 (P), 500 (P),(More)
Based on existing data and previous work, a series of studies is proposed as a basis toward a pragmatic early step in transforming toxicity testing. These studies were assembled into a data-driven framework that invokes successive tiers of testing with margin of exposure (MOE) as the primary metric. The first tier of the framework integrates data from(More)
BACKGROUND The Hershberger and male pubertal onset assays have been identified as possible Tier I screening tests to detect endocrine-active compounds (EACs). Both tests rely on changes in reproductive and/or accessory sex gland (ASG) weights in young animals. Because chemical treatment may affect growth rate, the relationship between body weight and(More)
The expression of a battery of trophoblast-specific mRNAs was studied during trophectoderm development in vivo and in vitro to assess the use of these mRNAs as markers of trophoblast differentiation and to examine lineage relationships between various trophectoderm derivatives. In situ hybridization of sectioned day 6.5-18.5 mouse embryos localized mRNAs(More)
These studies were designed to develop a coculture system using a simple medium to promote development of 1-cell bovine embryos through the 8-16-cell stage to morula and blastocyst stages. Monolayers for coculture were prepared from bovine oviduct epithelial cells (BOEC). In vivo-fertilized 1-2-cell embryos and ova (384) were surgically collected from(More)