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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
Based on the existing data, there is no evidence of reproductive and developmental toxicity. According to the Guidance on Information Requirements and Chemical Safety Assessment (section R7A Reproductive and Developmental toxicity, p370), no further data is required for the assessment of the developmental toxicity of ADCA.
• In the one-generation study on rats (Hatano Research Institute, 2000), no alert on reproductive toxicity has been highlighted after oral treatment at doses of 0, 100, 300 and 1000mg/kg. In parental animals, no ADCA-related effects were observed on abnormality in the oestrous cycle, the mating period, the number of vaginal estruses during the mating period, the fertility index, the number of parturition-related abnormality, the birth rate, the gestation period. The histology revealed no changes related to ADCA in the testes, pituitary glands, epididymides, seminal vesicle, coagulating glands, prostate, thyroids or kidneys in males. In females, no changes related to ADCA were noted in the pituitary glands, thyroids, ovaries, uterus, cervix, vagina or kidneys. The offspring showed no effects on general signs or symptoms, including behaviour and no effects on development. No morphological findings were observed to be ADCA related.
• A three-generation study in rats which received diets (bread) made of flour that had been treated with azodicarbonamide (100 mg/kg) showed no effect on fertility, reproduction or lactation in any generation (Oser et al. 1965, secondary sources: SIDS 2001, IPCS 1999). Given that azodicarboxamide is readily converted to biurea during the baking process, the relevance of this study could be questionable but results are supported by observations of a three-generation study in which rats were given diets containing up to 7500 mg biurea/kg (equivalent to approximately 450 mg/kg body weight per day). For each generation, rats were mated twice, and the first litter was sacrificed at weaning. From the second litter, 10 males and 10 females were chosen at random to form the parents for the next generation. The study finished with the weaning of the F3 generation. For each generation, fertility index (percentage of mating resulting in pregnancy), gestation index (number of pregnancies resulting in live litters), viability index (numbers of pups surviving 4 or more days), and lactation index (numbers of pups alive at 4 days surviving to weaning) were determined. No reproductive effects were observed (Oser et al., 1963; Oser et al., 1965).
• In a 13 week study by inhalation on rats at concentrations of 0, 50, 100 and 200mg/m3, no significant change in vaginal cytology was observed. In males, no effect was noted on the right caudal weight, the right epididymal weight, the right testicle weight, sperm motility, sperm count/weight of caudal tissue, or the incidence of abnormal sperm. An increase in sperm count was observed in rat treated at 50 and 100 mg/kg but cannot be relevant because is unrelated to the other observations in testicles (Medinsky et al., 1990). Conclusion: No evidence of any effect on the number and development of offspring in a one-generation study realised in rats at dose-levels of ADCA up to 1000mg/kg/d and in three-generation study in rats with ADCA at 100mg/kg/d and biurea, main metabolite of ADCA, at doses-levels up to 450mg/kg/d. This is supported by the absence of adverse effects on their post-natal development (during lactation) in the generational studies and the lack of adverse effects in sperm morphology in the 13-week inhalation study on rat. Based on these existing data, there is no evidence of reproductive and developmental toxicity. According to the REACh regulation, no further data is required for the assessment of the developmental toxicity of ADCA. The developmental tests can therefore be waived.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Effect of inhaled azodicarbonamide on F344/N rats and B6C3F1 mice with 2-week and 13-week inhalation exposures
Author:
Medinsky et al.,
Year:
1990
Bibliographic source:
Fundamental and Applied Toxicology 15, pages 308-319.
Reference Type:
publication
Title:
The fate of inhaled azodicarbonamide in rats.
Author:
Mewhinney J.A., Ayres P.H., Bechtold W.E. et al.
Year:
1987
Bibliographic source:
Fundam Appl Toxicol; 8 (3). 372-381.
Reference Type:
publication
Title:
Nutritional studies on rats on diets containing high levels of partial ester emulsifiers. 11. Reproduction and lactation.
Author:
Oser B, Oser M.
Year:
1963
Bibliographic source:
Journal of nutrition, 60:489-505.
Reference Type:
publication
Title:
Studies of the safety of azodicarbonamide as a Fluor-Maturing agent.
Author:
Oser, B.L.; Oser, M.; Morgareidge, K.
Year:
1965
Bibliographic source:
Toxicol. Appl. Pharmacol. 7, 445-472 (1965).
Reference Type:
study report
Title:
Unnamed
Year:
2000
Reference Type:
review article or handbook
Title:
OECD SIDS Initial assessment report for SIAM 12, 2001. Azodicarbonamide.
Author:
OECD
Year:
2001
Reference Type:
review article or handbook
Title:
IPCS, Concise International Chemical Assessment Document 16. Azodicarbonamide.
Author:
WHO
Year:
1999

Materials and methods

Results and discussion

Results (fetuses)

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion