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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study is classified as reliable without restriction because it was conducted according to the recommendations of OECD guideline 414.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report Date:
1997

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test compound: TPS 32
Chemical name: di-t-dodecyl polysulfide
CAS no.: 68425-15-0
Source: EAP
Batch: 96000424
Sulfur content 31.10%

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Duration of treatment / exposure:
Gestation day 6 to 15
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
50, 250 and 1000 mg/kg bw
Basis:

Control animals:
yes, concurrent vehicle
Details on study design:
Sex: female
Duration of test: up to gestation day 20

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
1 000 mg/kg bw/day
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

No clinical signs, no unscheduled deaths, no abortions or total  resorption were observed in any group. The food consumption and body  weight gain of the pregnant females from all treated groups were similar  to those of controls.

No treatment-related macroscopic findings were observed, in any group.  The post-implantation loss was similar in the 0,50 and 250 mg/kg-day  groups. 

In the 1000 mg/kglday group, a slightly increased post-implantation loss  (represented mainly by late resorptions, observed in one female) was  observed: it could not be demonstrated that this single event was  treatment-related. 
No treatment-related effects were observed on the number of live fetuses  per animal, the fetal body weight or the sex-ratio.  No treatment-related external anomalies or malformations were observed in  any group. 
No treatment-related soft tissue malformations or anomalies were noted in  any group.  No treatment-related skeletal malformations, anomalies or variations were  observed in any group.

Applicant's summary and conclusion

Conclusions:
TPS 32 , administered daily by the oral route at 50, 250 or 1000 mg/kg/day to pregnant Sprague-Dawley female rats during organogenesis did not show any signs of toxicity in the pregnant female and did not produce any embryotoxicity, fetotoxicity or teratogenic effects. At 1000 mg/kg/day, only a slight increase in post-implantation loss was noted, as a contribution of a single female: it could not be demonstrated that this single event was treatment-related. The No Effect Level is defined as 1000 mg/kg/day in terms of maternotoxicity, embryofetotoxicity and teratogenic effects.
Executive summary:

In an OECD TG 414 study, three groups of 25 mated female rats received di-tert-dodecyl polysulfides (TPS 32), by oral gavage at the dose levels of 50, 250 or 1000 mg/kg/day, each day from day 6 to day 15 post-coitum inclusive. Simultaneously, a group of 25 mated females was given the vehicle alone (0.5% carboxymethylcellulose) under the same conditions and acted as a control group. Clinical signs including (including evidence of abortion/resorption) and mortality were checked daily. Food consumption and body weight were recorded at designated intervals during pregnancy. On day 20 post-coitum, females were killed. The gravid uterus was weighed and fetuses were removed by hysterectomy. Females were examined macroscopically. Litter parameters were recorded: number of corpora lutea, implantation sites, resorptions, dead and live fetuses. The live fetuses were weighed, sexed, submitted to an external examination and then to soft tissue or skeletal examinations.

No clinical signs and no unscheduled deaths were observed in any group. No females aborted or presented total resorption in any group. The food consumption and body weight gain of the pregnant females from all treated groups were similar to those of controls. No treatment-related macroscopic findings were observed, in any group.The post-implantation loss was similar in the 0, 50 and 250 mg/kg/day groups. In the 1000 mg/kg/day group, a slightly increased post-implantation loss (represented mainly by late resorptions, observed in one female) was observed: it could not be demonstrated that this single event was treatment-related. No treatment-related effects were observed on the number of live fetuses per animal, the fetal body weight or the sex-ratio. No treatment-related external, soft tissue and skeletal anomalies or malformations were observed in any group.

 

The No Effect Level is defined as 1000 mg/kg/day in terms of maternotoxicity, embryofetotoxicity and teratogenic effects.