In a 90-day toxicity study in rats, di-(2-ethylhexyl)phthalate (
DEHP) produced testicular
atrophy. To characterise further the testicular toxicity of
phthalate esters the effect of age on the induction of testicular
atrophy has been examined as well as the reversibility of the lesions and the effects of certain other
phthalate esters. Seminiferous tubular
atrophy, comprising a loss of spermatids and spermatocytes, resulted when 4-week-old rats were given 10 daily doses of
DEHP. In similarly treated 10-week old rats up to 50% of tubules were atrophic while the remainder were unaffected. No testicular damage was produced in 15 week-old rats. The lesion produced in 4-week-old rats was reversible whether treatment was stopped prior to, or continued until after the control rats had reached sexual maturity. Normal testicular weight and histology were restored within 12 and 20 weeks respectively. Of a series of di-n-alkyl phthalates from dimethyl to di-n-octyl, the butyl, pentyl and hexyl
esters produced testicular lesions similar to
DEHP. The testicular effects of
DEHP were not influenced by simultaneous administration of
testosterone or
follicle stimulating hormone (FSH). The mechanism by which
phthalate esters exert their effects is discussed in the context of a possible action on Sertoli cell function.