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EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS
GRAY, L. E., K. HOWDESHELL, J. FURR, C. R. LAMBRIGHT, T. E. STOKER, V. S. WILSON, AND N. C. NORIEGA. EXPOSURE TO DIETHYL HEXYL PHTHALATE (DEHP) DELAYS PUBERTY AND REDUCES ANDROGEN-DEPENDENT TISSUE WEIGHTS IN LONG EVANS HOODED AND SPRAGUE DAWLEY MALE RATS. Presented at Society for the Study of Reproduction, Quebec, QC, CANADA, July 24 - 27, 2005.
DEHP is a plasticizer that alters sexual differentiation in the male rat by reducing fetal Leydig cell testosterone synthesis and insl3 mRNA levels. When exposure includes the pubertal stage of life, DEHP and other phthalates delay puberty and reduce androgen-dependent tissue weights in the SD rat. In contrast, a recent publication claimed that DEHP elevated testosterone levels in LE male rats and proposed that DEHP would accelerate, rather than delay, puberty at low dosage levels. The objective of the current study was to determine if DEHP treatment altered pubertal development similarly in LE and SD rats, or if there were stain specific responses or paradoxical effects at low dosage levels. In the current study, LE and SD rats were dosed by gavage with DEHP at 0, 10, 100, 300 or 900 mg/kg/d from weaning until necropsy at 56 or 100 days of age. DEHP treatment delayed puberty at 300 and 900 mg/kg/d in both rat strains. There was no evidence for a low dose androgenic effect of DEHP in either rat strain. Both strains of rats had reduced androgen-dependent organ weights in the high dose groups but the effects were more robust at 56 days of age than at 100 days of age. Serum LH was increased and testosterone tended to decrease in the high dose group. There were some strain differences in the magnitude of the effects of DEHP. Whereas, puberty and some of the androgen-dependent tissues were more affected in LE rats than in SD rats, testes weights were more affected in SD rats. In summary, pubertal DEHP treatment did not accelerate puberty, or increase serum testosterone or androgen dependent tissues weights in either rat strain at any dosage level. In fact, all the effects of DEHP appear "antiandrogenic". Pubertal DEHP treatment inhibits Leydig cell testosterone production during puberty, delaying the onset of preputial separation and reducing androgen-dependent tissue weights in both LE and SD rats. Abstract of a proposed presentation and does not necessarily reflect EPA policies.