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© 1989 Oxford University Press

research-article

Reproductive Toxicity of Three Phthalic Acid Esters in a Continuous Breeding Protocol

JERROLD J HEINDEL, DUSHYANT K GULATI*, ROBIN C MOUNCE*, SUSAN R RUSSELL* and JAMES C LAMB, IV1

Developmental and Reproductive Toxicology Group, National Toxicology Program, National Institute of Environmental Health Sciences P.O. Box 12233. Research Triangle Park, North Carolina 27709 *Environmental Health Research and Testing, Inc. 2514 Regency Road, Lexington, Kentucky 40503

Received May 2, 1988; accepted August 19, 1988

Reproductive Toxicity of Three Phthalic Acid Esters in a Continuous Breeding Protocol. HEINDEL, J. J., GULATI, D. K., MOUNCE, R. C., RUSSELL, S. R., AND LAMB, J. C., IV. (1989), Fundam. Appl Toxicol. 12, 508–518. A continuous breeding protocol was utilized to examine the reproductive toxicity of three phthalate esters. CD-1 mice were given diets with either di-n-propyl phthalate (DPrP:0.0, 1.25, 2.5, or 5.0%), di-n-pentyl phthalate(DPP:0.0,0.5, 1.25, or 2.5%), or di-n-octyl phthalate (DOP: 0.0, 1.25, 2.5, or 5.0%). Both male and female mice (20 pairs per treatment group. 40 pairs of control animals) were dosed for 7 days prior to and during a 98-day cohabitation period. Reproductive function was evaluated during the cohabitation period by measuring number of litters per pair, live pups per litter, and pup weight. There was no apparent effect on reproductive function in the animals exposed to DOP at dose levels sufficient to cause a significant increase in liver weight. Both DPP and DPrP were toxic to the reproductive system as evidenced by a complete inhibition of fertility at 1.25 and 2.5% DPP or 5.0% DPrP, and reduced fertility (litters/pair and live pups/litter, 0.5% DPP; live pups/litter, 2.5% DPrP). Toxicity of DPP had a strong male component and female component, whereas DPrP was more toxic to the female than the male reproductive system. DPP and DPrP treatment was associated with decreased body weight, increased liver weight, decreased testis and epididymis weights, decreased epididymal sperm concentration, and elevated seminiferous tubule atrophy. A comparison of seven phthalate esters tested using this continuous breeding protocol indicates the relative order of reproductive toxicity as diethylhexyl, dihexyl, dipentyl, dibutyl, dipropyl; diethyl and dioctyl are nontoxic.


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