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Administrative data

Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Dose descriptor:
NOAEL
130 mg/kg bw/day
Additional information

The effect of DCP on the reproductive performance of male and female S-D rats was investigated in a GLP-compliant, guideline, 2-generation study (Dow, 1990). PDC was administered in drinking water at levels of 0%, 0.024%, 0.1% or 0.24% (w/v), equivalent to received doses of 20- 30, 70-130 or 130-250 mg/kg bw/day, respectively, for the parental generations; females received higher doses during lactation, equivalent to approx. 60, 200 and 450-500 mg/kg bw/day. Water consumption was decreased 20-50% in the mid- and high dose groups, possibly reflecting poor palatability linked to the presence of DCP. Gestational body weight gain was reduced by approx. 20% in high dose dams and 7-13% in mid dose females. Treatment-related hepatocellular granularity, considered an adaptive change by the study pathologist, was present in males and females of both generations at all dose levels (incidence in high dose animals: <17% in females; <13% for males). All other tissues, including reproductive organs from both sexes, were unremarkable.

 

Despite the observed effects, reproductive function was unaffected in males and females of both generations. Although neonatal body weight was decreased, and neonatal mortality increased, in litters from high-dose dams consuming up to 250 mg/kg bw/d during pregnancy or up to 500 mg/kg bw/d during lactation, this appears secondary to maternal dehydration and a 20% reduction in gestational body weight gain, rather than a direct effect on reproduction. Live births, litter sizes and other pup parameters were unremarkable. Based on these findings, the study demonstrated a parental NOAEL of 20-30 mg/kg bw/day (0.024%; based upon body weight effects), a NOAEL in the offspring of 70-130 mg/kg bw/day (0.1%), and a reproductive NOAEL of 130-250 mg/kg bw/day (0.24%). Overall this study provides no evidence that PDC selectively targets the male or female reproductive system.


Short description of key information:
Overall well-conducted studies provide no evidence that DCP selectively targets the male or female reproductive systems.

Effects on developmental toxicity

Description of key information
Overall, results from well-conducted developmental toxicity studies in rats and rabbits demonstrated the occurrence of mild foetotoxicity (delayed ossification) coincident with maternal toxicity. DCP was not teratogenic under the conditions of these investigations.
Effect on developmental toxicity: via oral route
Dose descriptor:
NOAEL
150 mg/kg bw/day
Additional information

The potential effects of DCP on embryonal/foetal development were investigated in two species by Kirk et al. (1995) in two GLP-compliant guideline studies. Pregnant S-D rats were treated with 0, 10, 30 or 125 mg/kg bw/day PDC in corn oil (gavage) on gestation days 6-15 inclusive and fetuses examined on GD 20, while pregnant New Zealand White rabbits received 0 (corn oil vehicle), 15, 50 or 150 mg/kg bw/day on GD 7-19, inclusive, followed by a fetal examination on GD 28.

 

Clear signs of maternal toxicity were present in high dose animals of both species. Rats given 125 mg/kg bw/day exhibited clinical signs (decreased movement and muscle tone, lacrimation, salivation) on GD 6 and 7, with an approx. 25% reduction in food and water consumption and a 30% reduction in body weight gain over the entire treatment period. Rabbits given 150 mg/kg bw/day showed a statistically significant net reduction in mean body weight gain on GD 7-20 (decreased 165 g) while controls showed a net gain (49 g) during the same period. Hematological changes were also noted in high dose rabbits (not evaluated in rats), with an approx. 20% reduction in red cell counts, hemoglobin concentration and hematocrit, while platelet and white cell counts were increased by 20-25%. Foetal examination revealed a similarly low incidence of variations in control and treated groups of both species; the only treatment-related finding was a significant increase in delayed ossification of the bones of the skull in high dose rats and rabbits, indicative of a developmental delay. There was no evidence of any teratogenic effect.

Justification for classification or non-classification

DCP did not cause effects on fertility as judged in a two-generation reproductive toxicity study in rats. Results from well-conducted developmental toxicity studies in rats and rabbits demonstrated the occurrence of mild foetotoxicity (delayed ossification) coincident with maternal toxicity. DCP was not teratogenic under the conditions of these investigations. Overall, classification for effects to reproduction (fertility, developmental effects)