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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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Partially natural parturition.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Reference substance name:
Sulfuric acid, mono-C12-14-alkyl esters, sodium salts
EC Number:
287-809-4
EC Name:
Sulfuric acid, mono-C12-14-alkyl esters, sodium salts
Cas Number:
85586-07-8
Molecular formula:
C12-14H25-29SO4Na
IUPAC Name:
Sulfuric acid, C12-14-alkyl (even numbered) esters, sodium salts

Test animals

Species:
rat
Strain:
Wistar
Details on test animals or test system and environmental conditions:
According to Guideline.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on exposure:
Concentration in vehicle: 10%
Analytical verification of doses or concentrations:
yes
Details on mating procedure:
According to Guideline.
Duration of treatment / exposure:
Day 6-15 of gestation.
Frequency of treatment:
Once daily.
Duration of test:
Day 21 and Post parturition, resp.
Doses / concentrationsopen allclose all
Dose / conc.:
63 mg/kg bw/day (actual dose received)
Dose / conc.:
125 mg/kg bw/day (actual dose received)
Dose / conc.:
250 mg/kg bw/day (actual dose received)
Dose / conc.:
500 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
20 females (15 for dissection; 5 for natural parturition)
Control animals:
yes, concurrent vehicle

Examinations

Maternal examinations:
Acording to Guideline, except for parturition. Except of killing one day prior to the expected day of delivery, five of 20 dams were allotted to natural parturition before sacrifice.
Ovaries and uterine content:
The ovaries and uterine content was examined after termination: Yes

Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes

- Other: Five mated rats from each of the treatment and ten from the control group were selected by random numbers for natural parturition. This enabled observations on litter size, weight and infant mortality to be recorded, together with any other observable postpartum expression of response to treatment for a period of 21 days (birth to weaning).
Fetal examinations:
- External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: No
Statistics:
Yes

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yes

Details on maternal toxic effects:
At 500 mg/kg bw/day, the test substance produced maternal toxicity associated with severe diarrhoea, reduced food intake and reduced body weight gain. There was one death in this group and two animals were killed prior to full term. The survivors showed an increased number of intrauterine deaths and a reduction in live foetal body weight. These foetuses showed evidence of toxic retardation, with delayed ossification and also an increased incidence of supernumerary cervical ribs and shortened thoracic ribs. There were no gross external or visceral anomalies which could be attributed to treatment.
No maternal toxic effects were seen in the other treatment groups and there were no effects on live foetal numbers, body weight or crown-rump distance. There was no evidence of a specific external, gross viscera1 or skeletal defect which could be attributed to treatment.
There was no indication of a treatment effect on pups born by natural parturition and reared to weaning age of 21 days.

Effect levels (maternal animals)

Key result
Dose descriptor:
NOEL
Remarks:
systemic
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: No toxic effects.

Results (fetuses)

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

Details on embryotoxic / teratogenic effects:
Effects were only seen in the presence of maternal toxicity.85586-07-8

Effect levels (fetuses)

Key result
Dose descriptor:
NOEL
Remarks:
development
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: No toxic effects.

Overall developmental toxicity

Developmental effects observed:
yes
Lowest effective dose / conc.:
500 mg/kg bw/day (actual dose received)
Treatment related:
yes
Relation to maternal toxicity:
developmental effects as a secondary non-specific consequence of maternal toxicity effects

Applicant's summary and conclusion

Conclusions:
Treatment of pregnant rats with the test substance at 500 mg/kg bw/day induced a maternal toxic response and this was reflected in the conception which showed toxic retardation.
At 250, 125 and 63 mg/kg bw/day, the test substance did not cause maternal toxicity or foetotoxicity and did not show teratogenic potential.