A Study of the Developmental Toxicity Potential of Pentachlorophenol in the Rat

Abstract

Pentachlorophenol (penta, CAS #87-86-5) is primarily used as a wood preservative. As part of the USEPA pesticide reregistration process, the developmental toxicity (embryo-fetal toxicity and teratogenic potential) of commercially available penta was studied following oral gavage to presumed pregnant female Sprague-Dawley rats (Crl:CD BR VAF/Plus Subdivision F, 83-3). Both study design and penta purity met the requirements of the USEPA. Doses of 0 (corn oil), 10, 30, and 80 mg/kg/day were administered to the rats at concentrations of 0, 2, 6, and 16 mg/ml, respectively from day 6 to day 15 of presumed gestation. The dosage volume was 5 ml/kg, adjusted on each day of dosage based on individual body weights recorded immediately before intubation. The rats were sacrificed on day 20 of presumed gestation and necropsied. The number of corpora lutea in each ovary was recorded. The uterus was examined for pregnancy, number and distribution of implantations, early and late resorptions and live and dead fetuses. Each fetus was weighed, sexed, and examined for gross external, soft tissue and skeletal alterations. The no-observable-adverse-effect-level (NOAEL) for maternal toxicity in rats was determined to be 30 mg/kg/day of penta. The developmental NOAEL for penta in rats was also found to be 30 mg/kg/day. The lowest-observable-adverse-effect-level (LOAEL) for penta developmental toxicity (80 mg/kg/day) was associated with increased resorptions, reduced live litter size and fetal body weights, and caused increased malformations and variations. These NOAELs, derived using USEPA approved study designs, are higher than those previously reported using penta that is no longer commercially available in studies with non-approved experimental designs. Penta should not be identified as a selective developmental toxicant in the rat because adverse effects on development of rat conceptuses occurred only at maternally toxic dosages.

Developmental Toxicity Study of Pentachlorophenol in the 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).…”

Antioxidant Effects of Pomegranate Seed Oil Against Pentachlorophenol Toxicity in Rat Tissues

“…Pomegranate extracts have effects like scavenging free radicals, reducing oxidative stress. This oil increases plasma antioxidant capacity and reduces cellular oxidative stress products and increases the levels of decreased GSH (5,26,32,41). In the studies regarding the protective effects of pomegranate products on experimental models of toxicity and disease, administration of pomegranate extract in liverdamaged rats caused elevation in CAT, SOD and GSH-Px enzyme activities and reduction in the formation of lipid peroxidation products in the liver (13).…”

“…In addition, fatty acids such as gallic acid, ellagic acid and punicic acid; flavonols and flavonol glycosides like quercetin, kaempferol, luteolin and apigenin; anthocyanins like delphinidin, cyanidin and pelargonidin; amino acids like methionine, valine and proline has protective features (3,9,13,15,32). PCP is a compound which has a wide spectrum of biocidal activity, which is widely used as antifungal, especially in the wood industry, and which continues to have a residue problem in the nutrients due to its extremely slow degradation in the environment (5,20). PCP is carcinogenic and genotoxic in various experimental animals and that these effects may be mediated by free oxygen radicals resulting from its biotransformation in the liver (43,50).…”

Prediction of embryotoxic potential using the ReProGlo stem cell-based Wnt reporter assay

“…Concerning the 23 test compound in question, we searched the available literature and found evidence for teratogenic effects occurring at the level of maternal toxicity only for the following compounds: monobutyltin trichloride, dibutyltin dichloride and tributyltin chloride [42], fenoxycarb [43], benomyl and carbendazim [44], endosulfan [45], glycolic acid [46], pentachlorophenol [47].…”