Bis(4-chlorophenyl) sulphone

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Description of key information

No data.

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

50 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

adequate

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

In a reproduction/developmental toxicity screening study (Safepharm Ltd, 2008) considered as key study, DCDPS in arachis oil was administered to 10 Sprague-Dawley rats/sex/dose level by oral gavage at 0 (vehicle only), 5, 15 or 50 mg/kg bw/day. Rats were dosed with DCDPS for two weeks maturation, pairing and pregnancy up to day 4 post partum, thus a total of 42 days. In the reproductive screening part of the study, males treated with 50 mg/kg bw/day showed a reduction in cumulative body weight gain throughout the treatment period and a reduction in weekly body weight gain during the first two weeks of treatment.Offspring from litters treated with 50 mg/kg bw/day showed a reduction in body weight gain considered as developmental effect. At necropsy, enlarged livers were seen in males at 15 mg/kg bw/day and in males and females at 50 mg/kg bw/day. Animals of either sex from all treatment groups showed an increase in liver weight. Dose-dependent centrilobular hepatocyte enlargement was seen in all treated groups. Centrilobular hepatocyte vacuolation was noted at 50 mg/kg bw/day being more prevalent in males. Based on these results, the NOAEL for parental toxicity was established at 15 and 50 mg/kg bw/day for male and female animals, respectively. The NOAEL for toxicity to reproduction/fertility was set at 50 mg/kg bw/day since no reproductive toxicity was seen.

DCDPS was examined extensively for repeated dose toxicity in rats and mice (14 -week and 2 -year feeding studies presented in section 7.5.1 "Repeated dose toxicity: oral"). In all studies the liver was identified as the main target organ and no substance related adverse effects were noted on reproductive organs (prostate gland, testis, epididymis, seminal vesicle, female mammary gland, clitoral gland, ovary, uterus) or hormonally active tissues which might influence reproduction at all dose levels.

Based on the available information it is concluded that DCDPS has no adverse effect on fertility. A further animal study addressing reproductive toxicity of DCDPS is not required.

Short description of key information:
Evidence that the reproductive system is not affected by DCDPS exposure was obtained from a reliable OECD 421 screening study and from repeated dose toxicity studies in rats and mice (14-week and 2-year studies).

Justification for selection of Effect on fertility via oral route:
Contemporary screening study available

Effects on developmental toxicity

Description of key information

A GLP guideline study on developmental/teratogenicity hazard showed no adverse developmental/teratologic effects of orally administered DCDPS.

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

180 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

High quality

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

A GLP OECD 414 guideline study was undertaken using orally administered DCDPS to Wistar rats, at doses of 20, 60 and 180 mg/kg bw/d during GD 6 - 19. The dams were sacrificed and necropsied on GD 20 with assessment of fetal development. Animals in the high dose group (180 mg/kg bw/d) showed decreased food consumption and decreased net body weight gain (p < 0.05). There were no effects on survival or gestational parameters. There were no adverse effects observed among fetuses either in soft tissue or skeletal malformations or variations. The NOAEL for maternal toxicity is 60 mg/kg bw/d, and the NOAEL for developmental toxicity is greater than or equal to 180 mg/kg bw/d.

 

The conclusion of no significant developmental toxicity is supported in a reproduction/developmental toxicity screening study (Safepharm Ltd, 2008). DCDPS in arachis oil was administered to 10 Sprague-Dawley rats/sex/dose level by oral gavage at 0 (vehicle only), 5, 15 or 50 mg/kg bw/day. In the developmental screening part of the study, high dose males (50 mg/kg bw/day) showed a reduction in cumulative body weight gain throughout the treatment period and a reduction in weekly body weight gain during the first two weeks of treatment. Offspring from litters treated with 50 mg/kg bw/day also showed a reduction in body weight gain. Animals of either sex from all treatment groups showed an increase in liver weight, associated with centrilobular hepatocyte enlargement. This is considered an adaptive effect rather than an adverse effect.

Justification for selection of Effect on developmental toxicity: via oral route:
GLP guideline study on developmental toxicity is available.

Toxicity to reproduction: other studies

Additional information

Guideline toxicity testing in rats demonstrates that DCDPS shows no developmental or reproductive toxicity effects.

Justification for classification or non-classification

Reproductive and developmental toxicity testing results on DCDPS demonstrate an absence of toxic effects. According to Regulation 1272/2008/EC, the criteria for classification as a reproductive toxicant are not fulfilled and so the substance is not classified.