title: Interpretation of studies on the developmental reproductive toxicology of 2,3,7,8-tetrachlorodibenzo-p-dioxin in male offspring.
abstract: There have been several studies on the maternal administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and effects in the reproductive tract of male offspring, subsequent to risk assessments undertaken in 2001. This review compares the methodology and results to examine key methodological features, and consistency in reported outcomes. Maternal dosing at >0.8 microg TCDD/kg causes lethality and weight loss, and it is difficult to distinguish between direct and indirect effects of TCDD at these dose levels. Statistically significant effects of maternal doses of <1 microg TCDD/kg (i.e. the dose levels relevant for risk assessment) on prostate weight or epididymal sperm counts in offspring were reported in the minority of studies. The pharmacokinetics of TCDD differs considerably between acute and chronic dosing, and with dose level of TCDD. On the basis of body burden, TCDD had different potency at inducing adverse effects in the only comparison study between acute and chronic dosing. Understanding of the pharmacokinetics of TCDD and relationship to adverse effects in offspring is required. These analyses identify key features of TCDD developmental toxicity in male offspring, and identify data needs for future risk assessment.
authors.affiliation: School of Biology, University of Nottingham, University Park, Nottingham, UK. david.bell@echa.europa.eu
authors.forename: David R
authors.initials: DR
authors.lastname: Bell
authors.forename: Sally
authors.initials: S
authors.lastname: Clode
authors.forename: Ming Qi
authors.initials: MQ
authors.lastname: Fan
authors.forename: Alwyn
authors.initials: A
authors.lastname: Fernandes
authors.forename: Paul M D
authors.initials: PM
authors.lastname: Foster
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: George
authors.initials: G
authors.lastname: Loizou
authors.forename: Alan
authors.initials: A
authors.lastname: MacNicoll
authors.forename: Brian G
authors.initials: BG
authors.lastname: Miller
authors.forename: Martin
authors.initials: M
authors.lastname: Rose
authors.forename: Lang
authors.initials: L
authors.lastname: Tran
authors.forename: Shaun
authors.initials: S
authors.lastname: White
mesh_terms: D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D000072317:Polychlorinated Dibenzodioxins / Q000493:pharmacokinetics / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015203:Reproducibility of Results; D012098:Reproduction / Q000187:drug effects*
chemical_list: D000072317:Polychlorinated Dibenzodioxins
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