Adverse effects of diisooctyl phthalate on the male rat reproductive development following prenatal exposure

Abstract

In a first study, rats were given diisooctyl phthalate (DIOP, CAS 27554-26-3) at 0, 0.1, 0.5, and 1g/kg/day, by gavage, on gestation days 6-20 (GD). There was a significant increase in resorptions at 1g/kg/day and a reduction in fetal weights at 0.5 and 1g/kg/day. Malpositioned testes were observed in fetuses at 1g/kg/day, and supernumerary lumbar ribs and ossification delay at 0.5 and 1g/kg/day. In a follow-up study, DIOP administered on GD 12-19 reduced fetal testicular testosterone at 0.1g/kg/day and above. Finally, postnatal reproductive assessment was conducted in adult male offspring prenatally exposed to DIOP on GD 12-21. Abnormalities of reproductive system (e.g. hypospadias, non scrotal testes, and hypospermatogenesis) were observed in a few adult males at 0.5g/kg/day, and with a high incidence at 1g/kg/day. Thus, DIOP displayed an antiandrogenic activity and disrupted the male reproductive development.

Keywords: AGD; Antiandrogen; BMD; DBP; DEHP; DIBP; DIDP; DINP; DIOP; DPP; Developmental toxicity; Diisooctyl phthalate; DnHP; DnOP; Embryotoxicity; GD; In utero exposure; LOAEL; Male reproductive system; NOAEL; PND; PNW; PVC; Phthalic acid esters; Rat; SD; anogenital distance; benchmark dose; di-n-butyl phthalate; di-n-hexyl phthalate; di-n-octyl phthalate; diethylhexyl phthalate; diisobutyl phthalate; diisodecyl phthalae; diisononyl phthalate; diisooctyl phthalate; dipentyl phthalate; gestation day; no-observed-adverse-effect level; polyvinyl chloride; postnatal day; postnatal week; standard deviation; the lowest-observed-adverse-effect level.