US EPA

5432712 

Journal Article 

Review 

Use of the Adverse Outcome Pathway (AOP) framework to evaluate species concordance and human relevance of Dibutyl phthalate (DBP)-induced male reproductive toxicity 

Arzuaga, X; Walker, T; Yost, EE; Radke, EG; Hotchkiss, AK 

2019 

1 

Reproductive Toxicology
ISSN: 0890-6238
EISSN: 1873-1708 

96 

445-458 

English 

31260805 

10.1016/j.reprotox.2019.06.009 

WOS:000582635800046 

http://www.sciencedirect.com/science/article/pii/S0890623819300693
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Dibutyl phthalate (DBP) is a phthalate ester used as a plasticizer, and solvent. Studies using rats consistently report that DBP exposure disrupts normal development of the male reproductive system in part via inhibition of androgen synthesis. However, studies using xenograft models report that in human fetal testis DBP exposure is unlikely to impair testosterone synthesis. These results question the validity of the rat model for assessment of male reproductive effects caused by DBP. The Adverse Outcome Pathway (AOP) framework was used to evaluate the available evidence for DBP-induced toxicity to the male reproductive system. Three relevant biological elements were identified: 1) fetal rats are more sensitive than other rodents and human fetal xenografts to DBP-induced anti-androgenic effects, 2) DBP-induced androgen-independent adverse outcomes are conserved amongst different mammalian models and human fetal testis xenografts, and 3) DBP-induced anti-androgenic effects are conserved in different mammalian species when exposure occurs during postnatal life stages. 

AOP; phthalates; testosterone; male reproductive