Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
subacute
Species:
rabbit

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral:

The objective of this study was to determine the potential toxicity of Cyclamen Aldehyde, when given orally via stomach tube for 14 consecutive days to male New Zealand White rabbits. In addition, potential effects on the male reproductive organs, including sperm parameters were assessed.

In the current study, Cyclamen Aldehyde at doses as high as 300 mg/kg/day did not result in any mortality or gross or microscopic lesions, and did not increase the incidence of clinical signs in the male rabbits. There were no apparent effects on body weight, body weight gains, food consumption or reproductive and non-reproductive organ weights. Cyclamen Aldehyde did not affect the cauda epididymal sperm count or sperm morphology. Individual sperm motility results, specifically the number of motile sperm and the total count of sperm from ejaculated semen samples, were highly variable but there were no noteworthy changes observed in comparison with concurrent and/or historical control values.

In conclusion, Cyclamen Aldehyde when administered orally to male rabbits for 14 days at dosages as high as 300 mg/kg/day did not produce any clinical observations, changes in body weight or food consumption or affect the weights of any reproductive or non-reproductive organs that were evaluated. There were no microscopic findings in the testes or epididymides at 300 mg/kg/day, and no noteworthy changes in sperm parameters were observed.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
the dermal and inhalatory routes were waived on scientific grounds due to the justifications listed below. As such the oral route haas been reported, and the data was available.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
In line with Column 2, point 8.6.1, Annex VIII of Regulation 1907/2006, a repeat-dose inhalation study does not need to be performed as the substance has low vapour pressure and high melting point, so the potential for the generation of inhalable forms is low. The use of this substance should not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and a repeat-dose inhalation study is not required. As an objective of Regulation EC No. 1907/2006 is to reduce, replace or refine animal testing, based on the above information and information in this dossier, it can be reasonably expected that inhalation exposure is not expected and as such, it is not warranted to test the hypothesis in animals.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
In line with Column 2, point 8.6.1, Annex VIII of Regulation 1907/2006, a repeat-dose inhalation study does not need to be performed as the substance has low vapour pressure and high melting point, so the potential for the generation of inhalable forms is low. The use of this substance should not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and a repeat-dose inhalation study is not required. As an objective of Regulation EC No. 1907/2006 is to reduce, replace or refine animal testing, based on the above information and information in this dossier, it can be reasonably expected that inhalation exposure is not expected and as such, it is not warranted to test the hypothesis in animals.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
The physicochemical and toxicological properties suggest low potential for significant rate of absorption through the skin. Furthermore the results of laboratory animal studies show low acute dermal toxicity. In the 28 - days repeated dose study via dietary administration does not exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can be extrapolated to repeated dermal route administration.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
The physicochemical and toxicological properties suggest low potential for significant rate of absorption through the skin. Furthermore the results of laboratory animal studies show low acute dermal toxicity. In the 28 - days repeated dose study via dietary administration does not exacerbate systemic toxicity effects which suggest bioavailability is low, thereby there is low toxicity potential. This intrinsic property/toxicity potential can be extrapolated to repeated dermal route administration.

Justification for classification or non-classification