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Two-Generation Oral (Diet) Reproductive Toxicity Study of Resorcinol Bis-Diphenylphosphate (Fyrolflex RDP) in Rats

Akzo Nobel Chemicals Inc., Dobbs Ferry, New York, USA

B. M. Ryan

ITT Research Institute, Chicago, Illinois, USA

R. Selby

ITT Research Institute, Chicago, Illinois, USA

S. Garthwaite

ITT Research Institute, Chicago, Illinois, USA

R. Morrissey

Pathology Associates International, Chicago, Illinois, USA

R. I. Freudenthal

West Palm Beach, Florida, USA

Fyrolflex resorcinol bis-diphenylphosphate (RDP) was evaluated in a two-generation reproductive study as part of a program to assess the overall toxicology of this flame retardant. RDP was administered to male and female Sprague-Dawley rats in the diet at concentrations of 1000, 10,000 or 20,000 ppm. The control group was given diet alone. Parental (P₁) animals were treated for 10 weeks prior to mating, during the 2-week mating period, throughout gestation, and through lactation until sacrifice. The F₁ generation (P₁ offspring) was treated following a regimen similar to P₁. The F₂ generation was not treated. No significant difference in Utter survival was observed between the control and treated groups. Body weights were significantly decreased in P₁ rats during the 1st week due to an initial flavor aversion of the test substance in the diet. Body weight, weight gains, and food consumption were decreased in the test substance-treated pups (F₁) during lactationand after weaning. These changes were also attributed to a flavor aversion. Anogenital distance was similar in the control and high-dose groups, whereas vaginal opening and preputial separation were delayed in the 10,000 and 20,000 ppm groups, and were considered to be secondary to the reduction in F₁ body weight. Neither parents nor offspring exhibited any test substance-related clinical signs of toxicity. Vaginal cytology and cyclicity and male reproductive functions (sperm count, motility, and morphology) were unaffected by treatment. Mating performance was similar in the treated groups relative to the control. No treatment-related lesions were noted in the reproductive organs. Increased liver weight and associated hepatic periportal hypertrophy were observed in the RDP-treated animals (P₁ and F₁). In conclusion, there were no adverse effects on reproductive performance or fertility parameters associated with RDP administration in the diet. Fyrolflex RDP administered for greater than 13 weeks and up to the entire life span (i.e., F₁, from conception to euthanasia) resulted in increased liver weights with associated periportal hypertrophy. This change was considered an adaptive process associated with RDP metabolism in the liver.

Key Words: Flame Retardant • Reproduction • Resorcinol Bis-Diphenylphosphate

International Journal of Toxicology, Vol. 19, No. 4, 243-255 (2000)
DOI: 10.1080/10915810050202051


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