Effect of different sampling designs on outcome of endocrine disruptor studies

• Published in: Reproductive toxicology (Elmsford, N.Y.) Vol. 14; no. 4; pp. 359 - 367
• Main Authors: Elswick, Barbara A., Welsch, Frank, Janszen, Derek B.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.2000; Elsevier
• Subjects: Animals; Benzhydryl Compounds; Biological and medical sciences; Bisphenol A; Computer Simulation; di- n-butyl phthalate; Dibutyl Phthalate - toxicity; Dose-Response Relationship, Drug; Endocrine disruptor; endocrine system; Environmental pollutants toxicology; Estrogen Antagonists - administration & dosage; Estrogen Antagonists - toxicity; Estrogens, Non-Steroidal - administration & dosage; Estrogens, Non-Steroidal - toxicity; False negative; False positive; Female; General aspects; Intralitter variability; Male; Medical sciences; Models, Theoretical; Organ Size - drug effects; Phenols - administration & dosage; Phenols - toxicity; Pregnancy; Prostate - drug effects; Prostate - pathology; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Sample Size; Sampling design; Statistical modeling; Toxicity Tests - methods; Toxicology; Ventral prostate; Water Supply; Bisphenol A; Statistical modeling; Ventral prostate; di- n-butyl phthalate; False positive; False negative; Intralitter variability; Endocrine disruptor; Sampling design; Bioassay; Rat; Chemical compound; Rodentia; Oral administration; Progeny; Pollutant; Vertebrata; Mammalia; Investigation method; Test; Animal; Selection criterion; Environment; Methodological bias; Detection
• ISSN: 0890-6238; 1873-1708
• DOI: 10.1016/S0890-6238(00)00092-7

In this article, we demonstrate how sampling strategy can influence the outcome of endocrine disruptor studies. In a study of the weak xenoestrogen bisphenol A (BPA), possible treatment-related effects on ventral prostate (VP) fresh weight were found in rat offspring at 6 months of age when only one or two male pups were randomly selected from each litter. In subsequent BPA and di- n-butyl phthalate studies, large intralitter variability of this specific end point was apparent when the VP weights from entire litter complements were examined. We modeled the effects of sampling 1, 2, or 3 pups from each litter using the full-litter complement data. When one pup was randomly selected, a substantial percentage of incorrect conclusions about the presence or absence of treatment effects occurred. These statistical modeling analyses raise significant concern about the selection of one pup per litter for highly variable end points.