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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:
supporting study
Study period:
November 1966
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
significant methodological deficiencies
Remarks:
The study is not well documented. No GLP study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1966

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Deviations:
yes
Remarks:
Number of animals per group 12 instead of 16 minimum; duration of treatment is not clear.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
- Physical state: a blue powder

Test animals

Species:
rat
Strain:
not specified
Details on test animals and environmental conditions:
-Age at study initiation: Female rats of approximately the same age.-Weight at study initiation: between 300 and 350g- Diet (e.g. ad libitum): oxoid breeding diet

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
no
Details on mating procedure:
Males were placed with respective females overnight and mating was confirmed by the presence of spermatozoo in vaginal smears, and this was designated the first day of pregnancy.
Duration of treatment / exposure:
7 days prior to mating
Frequency of treatment:
Every day
Duration of test:
The mothers were killed on the 22nd day of pregnancy
Doses / concentrationsopen allclose all
Dose / conc.:
10 mg/kg bw/day (nominal)
Remarks:
100 ppm in the diet
Dose / conc.:
100 mg/kg bw/day (nominal)
Remarks:
1000 ppm in the diet
Dose / conc.:
1 000 mg/kg bw/day (nominal)
Remarks:
10000 ppm in the diet
Dose / conc.:
10 000 mg/kg bw/day (nominal)
Remarks:
100000 ppm in the diet
No. of animals per sex per dose:
5 groups of 12 animals in eachGroup 1: no test material in dietGroup 2: 100 ppm in dietGroup 3: 1000 ppm in dietGroup 4: 10000 ppm in dietGroup 5: 100000 ppm in diet
Control animals:
yes

Examinations

Fetal examinations:
-Litter size-Weight of live young-Resorptions-MalformationsIn addition, foetuses from ten of the twelve animals of each group were cleared and stained with alizarin and examined for defects of the skeleton. The foetuses from the remaining two mothers were sent for histopathological examination. The following tissues were specially observed: eye, heart, liver, ossification centres.

Results and discussion

Results: maternal animals

General toxicity (maternal animals)

Mortality:
no mortality observed
Description (incidence):
There were no maternal deaths.
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
At higher concentrations 1000 mg/kg bw and 10000 mg/kg bw, there were pathological effects in the kidneys, stomach, intestine and bladder which one would associate with a high and prolonged intake of a siliceous earth.

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:yesDetails on maternal toxic effects:There were no maternal deaths.When fed in the diet of rats in a concentration up to 10000 ppm (1000 mg/kg/day), the test substance had no effects on the growth, blood cellular constituents and haemoglobin or on the main biochemical constituents of the blood and urine. No significant effect on the organ weights.At higher concentrations 1000 mg/kg bw and 10000 mg/kg bw, there were pathological effects in the kidneys, stomach, intestine and bladder which one would associate with a high and prolonged intake of a siliceous earth.

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
> 100 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
gross pathology

Results (fetuses)

Fetal body weight changes:
no effects observed
Description (incidence and severity):
Migrated Data from removed field(s)
Field "Fetal/pup body weight changes" (Path: ENDPOINT_STUDY_RECORD.DevelopmentalToxicityTeratogenicity.ResultsAndDiscussion.ResultsFetuses.FetalPupBodyWeightChanges): no effects observed
Reduction in number of live offspring:
no effects observed
Changes in litter size and weights:
no effects observed
External malformations:
effects observed, non-treatment-related
Description (incidence and severity):
No malformations were observed in the control and the top dose level. At 10 mg/kg bw /day dose level one foetus had its hind limbs flexed inwards and another was slightly oedematous. Both these foetuses were from the same mother. At 100 mg/kg bw/day dose level two foetuses from the same mother had all their limbs twisted. At 1000 mg/kg bw/day dose level one foetus had a hernia and another had its limbs slightly twisted.
Visceral malformations:
effects observed, non-treatment-related
Description (incidence and severity):
An increase in the pericardial space was observed in one foetus from the controls, two foetuses from one animal from the 1000 mg/kg bw/day dose level and three from one animal from the 10000 mg/kg bw/day dose level. No other abnormalities were detected.
Details on embryotoxic / teratogenic effects:
The test material has no teratogenic effects at the dose levels from 10 mg/kg bw/day to 1000 mg/kg bw/day.

Effect levels (fetuses)

Key result
Dose descriptor:
NOAEL
Effect level:
> 10 000 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
no effects observed

Overall developmental toxicity

Developmental effects observed:
no

Applicant's summary and conclusion

Conclusions:
The NOAEL maternal toxicity is > 100 mg/kg bw per day, the NOAEL teratogenicity is > 10000 mg/kg bw per day.
Executive summary:

The study was performed to assess the teratogenic activity of the test material according to a method similar to OECD guideline 414). It was given an oral administration of the test material mixed in their diet at four different dose levels (10, 100, 1000, 10000 mg/kg bw) to 5 different groups of 12 female rats in each (a total of 60) during 7 days prior to mating. No maternal deaths and no teratogenical effects were observed. Results of the investigations confirm that the test material has not teratogenic activity.

The NOAEL maternal toxicity is > 100 mg/kg bw per day

The NOAEL teratogenicity is > 10000 mg/kg bw per day