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Key value for chemical safety assessment

Effects on fertility

Description of key information
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Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no experimental nor literature toxicological data available on TATD-CLE. Therefore the read across approach was considered in order to trace a complete toxicological profile of the substance.

RA: Cefuroxime (EC: 259-560-1; CAS: 55268-75-2)

Pregnancy Category B. Reproduction studies have been performed in mice at doses up to 3200 mg/kg/day (14 times the recommended maximum human dose based on mg/m2) and in rats at doses up to 1000 mg/kg/day (9 times the recommended maximum human dose based on mg/m2) and have revealed no evidence of impaired fertility or harm to the foetus due to cefuroxime axetil. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Reference

NLM/FDA Drug Labelling. CEFTIN (cefuroxime axetil) powder, for suspension. Labeler - GlaxoSmithKline LLC (167380711). Rev. 2011.


Short description of key information:
No adverse effects on the fertility are expected.

Effects on developmental toxicity

Description of key information
No developmental toxicity is expected.
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

There are no experimental nor literature toxicological data available on TATD-CLE. Therefore the read across approach was considered in order to trace a complete toxicological profile of the substance.

RA: Cefalonium (EC: 226-948-7; CAS: 5575-21-3)

In an oral teratogenicity study in rats no teratogenic effects were observed at doses of 20, 200 and 2000 mg cefalonium/kg bw. The NOEL for embryotoxicity and teratogenicity therefore was 2000 mg/kg, the highest dose tested. Food and water intake were, respectively, statistically significantly lower and higher in both mid and high dose treated dams. Caecum weight was increased in drug treated dams at all dose levels[1].

RA: Cefuroxime (EC: 259-560-1; CAS: 55268-75-2)

Pregnancy Category B. Reproduction studies have been performed in mice at doses up to 3200 mg/kg/day (14 times the recommended maximum human dose based on mg/m2) and in rats at doses up to 1000 mg/kg/day (9 times the recommended maximum human dose based on mg/m2) and have revealed no evidence of impaired fertility or harm to the foetus due to cefuroxime axetil. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed[2].

A review containing results of teratogenicity tests of fifteen cephalospirins shoed little evidence for teratogenicity of members of this group in general. In addition, studies were provided on parenteral reproductive toxicity of cefuroximine and ceftazidime. In these studies no teratogenic effects were found and no evidence was found for general reproductive toxicity (fertility and peri and post natal development). The main effects found were changes of food and water intake of dams and increased caecum weight of dams and pups. Taking into consideration the provided information on the general absence of teratogenic effects and reproduction toxicity in cephalosporins, no further teratogenicity and reproduction data were considered necessary[1].

Reference

[1 ]EMEA, Committee for veterinary medicinal products. Cefalonium. Summary report. EMEA/MRL/646/99-Final.August 1999.

[2]NLM/FDA Drug Labelling. CEFTIN (cefuroxime axetil) powder, for suspension. Labeler - GlaxoSmithKline LLC (167380711). Rev. 2011.

Toxicity to reproduction: other studies

Additional information

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Justification for classification or non-classification

According to CLP regulation (EC1272/2008), 3.7 reproductive toxicity section, reproductive toxicity includes adverse effects on sexual function and fertility in adult males and females, as well as developmental toxicity in the offspring. The definitions presented are adapted from those

agreed as working definitions in IPCS/EHC Document No 225, Principles for Evaluating Health Risks to Reproduction Associated with Exposure to Chemicals.

Reproductive toxicity of TADT-CLE has been evaluated on the basis of the read across with analogues. Studies on animals did not revealed any reasons of concern for fertility nor for the developmental toxicity. There are, however, no adequate and well-controlled studies in pregnant women.

In conclusion, according to CLP regulation (EC1272/2008), TADT-CLE is not classified for the reproductive toxicity.

Additional information