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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
other: read across from analogue substance
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: full study is available; only summary inserted

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2010
Reference Type:
study report
Title:
Unnamed
Year:
1978

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 414 (Prenatal Developmental Toxicity Study)
Principles of method if other than guideline:
In a developmental toxicity study, groups of 35 pregnant rats were fed Brown FK at dietary concentrations of 0, 0.03, 0.15, or 0.6 % (equivalent to 0, 15, 75, or 300 mg/kg bw/day) from day 0-19 days
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Reference substance name:
Similar Substance 4
IUPAC Name:
Similar Substance 4

Test animals

Species:
rat
Strain:
Wistar

Administration / exposure

Route of administration:
oral: gavage
Details on exposure:
daily
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
0-19 of pregnancy
Frequency of treatment:
daily
Duration of test:
21 days
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Dose / conc.:
15 mg/kg bw/day (actual dose received)
Dose / conc.:
75 mg/kg bw/day (actual dose received)
Dose / conc.:
300 mg/kg bw/day (actual dose received)
No. of animals per sex per dose:
35 pregnant females per each dose
Control animals:
yes, concurrent no treatment
Details on study design:
In a developmental toxicity study, groups of 35 pregnant rats were fed Brown FK at dietary concentrations of 0, 0.03, 0.15, or 0.6 % (equivalent to 0, 15, 75, or 300 mg/kg bw/day) from day 0-19 post coitus. Additional groups received 0.6% sodium chloride (salt control) or aspirin (250 mg/kg bw/day) (positive control). Five animals at each dose level were allowed to litter normally and the offspring were raised to weaning, while the remaining animals in each group were sacrificed at Gestation Day (GD) 17 and the fetuses removed by Caesarean section. Two-thirds of the fetuses were examined for gross soft-tissue abnormalities, then cleared and stained with Alizarin red for examination for skeletal defects. The remaining one-third of animals was examined for soft tissue defects

Examinations

Maternal examinations:
No abnormalities in condition or behaviour of the dams were observed.
Fetal examinations:
Soft tissue abnormalities or skeletal defects were not observed in any of the sacrificed fetuses or weaned animals

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:
> 300 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
clinical signs
mortality

Results (fetuses)

Skeletal malformations:
no effects observed
Visceral malformations:
no effects observed
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Effect levels (fetuses)

Dose descriptor:
NOAEL
Effect level:
> 300 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
skeletal malformations
visceral malformations

Overall developmental toxicity

Developmental effects observed:
no
Lowest effective dose / conc.:
300 mg/kg bw/day (actual dose received)

Applicant's summary and conclusion

Conclusions:
The analogue substance was tested following a study desgin equivalent to OECD 414. Under the experimental conditions the NOAEL is equal to 300 mg/kg bw /day.
Executive summary:

In a developmental toxicity study, groups of 35 pregnant rats were fed Brown FK at dietary concentrations of 0, 0.03, 0.15, or 0.6 % (equivalent to 0, 15, 75, or 300 mg/kg bw/day) from day 0-19

post coitus. Additional groups received 0.6% sodium chloride (salt control) or aspirin (250 mg/kg bw/day) (positive control). Five animals at each dose level were allowed to litter normally and the

offspring were raised to weaning, while the remaining animals in each group were sacrificed at Gestation Day (GD) 17 and the fetuses removed by Caesarean section. Two-thirds of the fetuses were

defects. Soft tissue abnormalities or skeletal defects were not observed in any of the sacrificed fetuses or weaned animals examined for gross soft-tissue abnormalities, then cleared and stained with Alizarin red for examination for skeletal defects. The remaining one-third of animals was examined for soft tissue