Oral (Gavage) Two-Generation (One Litter Per Generation) Reproduction Study of Pentachlorophenol (Penta) in Rats

Abstract

The potential for pentachlorophenol (penta) to induce general and reproductive/developmental toxicity was evaluated in Crl Sprague-Dawley rats, employing a two-generation reproduction toxicity study. Penta was administered by gavage at doses of 0, 10, 30, and 60 mg/kg/day. In both generations, the parental animals (30/sex/group) were intubated daily for 10 weeks before cohabitation and continuing through cohabitation, gestation, and lactation periods. Intubation of the F1 generation was begun 28 days postpartum. Animals were evaluated daily for mortality and general toxicity (clinical observations, body weights and gains, feed consumption). Organ weights were recorded and histopathological evaluations were made. Specific indices of reproductive function evaluated included estrous cycles, mating and fertility, parturition, lactation, viability, and growth and development of offspring, including sexual maturation, sperm parameters, and numbers of ovarian primordial follicles. All deaths in the parental rats were unrelated to penta. Expected metabolic effects of penta, sporadic increased liver weights associated with hepatocellular centrilobular hypertrophy and vacuolation and lipofuscin pigmentation, were evident in the 10-, 30-, and 60-mg/kg/day dose group P1 and F1 animals. Toxicity, in the form of liver pathology (single cell necrosis), reduced body weights and associated reductions in organ weights, and reduced feed consumption were noted in both generations at the 30- and 60-mg/kg/day doses. Developmental toxicity associated with these doses included reduced pup weights and viability. The 60-mg/kg/day dose also resulted in delayed sexual maturation, decreased spermatid counts, small prostates and testes, decreased implantations, reduced fertility, and increased resorptions of embryos. Based on these results, it was concluded that 30 mg/kg/day is the lowest-observable-adverse-effect level (LOAEL) and 10 mg/kg/day is the no-observable-adverse-effect level (NOAEL) for both reproductive and general toxicity. These findings are consistent with results from previously conducted studies wherein reproductive/developmental toxicity was observed only at doses that also induced general toxicity. It differs from previous findings in that the NOAEL for general toxicity is two to three times higher for the more pure product than for products produced and tested previously. In addition, the results did not indicate bioaccumulation of penta. Thus, penta did not selectively affect reproduction or development of the offspring of rats at a dose of 10 mg/kg/day, a dose that is 7000 to 20,000 times higher than human exposure.

Developmental exposure to pentachlorophenol affects the expression of thyroid hormone receptor β1 and synapsin I in brain, resulting in thyroid function vulnerability in rats

“…In our study, however, developmental PCP treatment did not affect plasma ir-inhibin, plasma testosterone, plasma LH, plasma FSH, or sperm production. In contrast, neonatal high-dose PCP treatment (30 or 60 mg kg -1 day -1 ) led to small testes, decreased spermatid count, and delayed sexual maturation in rats [57]. However, this reproductive disability in animals given high-dose PCP may be attributable to toxicity, in light of concurrent induced liver weight with histopathologic toxicity, reduced body weight, and reduced feed consumption.…”

Developmental Toxicity Study of Pentachlorophenol in the Rabbit

“…These conclusions were based upon the fact that the NOAELs for general toxicity and developmental toxicity were the same and the LOAELs for general toxicity and developmental toxicity were the same. Speci cally, (1) the LOAEL for maternal toxicity (e.g., reduced body weights, organ weights, and food consumption) and expected maternal metabolic effects (e.g., increased liver weights, heptaocellular centrilobular hypertrophy, and vacuolation) was the middle dose tested (30 mg/kg/day), as was the LOAEL for developmental toxicity (i.e., reduced pup weights and viability), and (2) the NOAEL was the lowest dose tested (10 mg/kg/day), as was the NOAEL for developmental toxicity (Bernard et al 2001a).…”

“…These studies included one that evaluated reproduction in a multigeneration rodent study and two that evaluated developmental toxicity, one in the rodent (rat) and one in the nonrodent (rabbit). In the multigeneration study, it was concluded that penta was not a reproductive toxicant because the LOAEL and the NOAEL (10 and 30 mg/kg/day, respectively) were the same for reproductive effects and general toxicity (Bernard et al 2001a). In the rat developmental study, penta was not a selective developmental toxicant because the no-observable-effec t (NOEL) for both general toxicity in the dam and developmental effects in the fetus was 30 mg/kg/day (Bernard, Ranpuria, and Hoberman 2001b).…”

Sertoli cell as a model in male reproductive toxicology: Advantages and disadvantages

“…Rams exposed to PCP displayed atrophy of seminiferous tubules as well as decreased spermatocytes production (Beard et al ., ). Similarly, PCP induced delayed sexual maturation, low spermatid counts and reduced testes weight in rats (Bernard et al ., ).…”