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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 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:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Partially natural parturition.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trade name
- Physical state: No data
- Analytical purity: 100%
- Lot/batch No.: No data
- Storage condition of test material: No data


Test animals

Species:
rat
Strain:
Wistar
Details on test animals 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 / concentrations
Remarks:
Doses / Concentrations:
0, 63, 125, 250, 500 mg/kg
Basis:
nominal conc.
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)

open allclose all
Dose descriptor:
NOEL
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: maternal toxicity
Dose descriptor:
NOEL
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Basis for effect level:
other: developmental toxicity

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)

Dose descriptor:
NOAEL
Effect level:
>= 250 mg/kg bw/day (actual dose received)
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: Embryotoxic / teratogenic effects:no effects Details on embryotoxic / teratogenic effects: Effects were only seen in the presence of maternal toxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Treatment of pregnant rats with Alfol 12-14 sulphate 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, Alfol 12-14 sulphate did not cause maternal toxicity or foetotoxicity and did not show teratogenic potential.