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

•Effects of DIOP (DIOP, CAS 27554-26-3) were examined in rats after prenatal exposure.•DIOP induced dose-related reduction of fetal testicular testosterone production.•DIOP produced reproductive abnormalities in male fetal and adult offspring. In a first study, rats were given diisooctyl phthalate (...

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Published in:Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2013-12, Vol.42, p.192-202
Main Authors: Saillenfait, Anne-Marie, Sabaté, Jean-Philippe, Robert, Alain, Cossec, Benoit, Roudot, Alain-Claude, Denis, Flavien, Burgart, Manuella
Format: Article
Language:English
Subjects:
Animals
Antiandrogen
Developmental toxicity
Diisooctyl phthalate
Dose-Response Relationship, Drug
Embryotoxicity
Female
In utero exposure
Male
Male reproductive system
Maternal-Fetal Exchange
Phthalic acid esters
Phthalic Acids - toxicity
Plasticizers - toxicity
Pregnancy
Rat
Rats
Rats, Sprague-Dawley
Reproduction - drug effects
Testis - drug effects
Testis - metabolism
Testis - pathology
Testosterone - metabolism
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Summary:•Effects of DIOP (DIOP, CAS 27554-26-3) were examined in rats after prenatal exposure.•DIOP induced dose-related reduction of fetal testicular testosterone production.•DIOP produced reproductive abnormalities in male fetal and adult offspring. 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.
ISSN:0890-6238
1873-1708
DOI:10.1016/j.reprotox.2013.09.004