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Description of key information

Repeated dose toxicity - oral

No adverse effects were observed in male and female rats in a 28 days and a 90 days repeated dose toxicity test conducted according to OECD 407 and OECD 408 respectively (Calvert Laboratories, Inc., 2011 and Envigo Research Limited, 2018) in which animals were exposed orally (gavage) to 0, 100, 500 or 1000 mg/kg bw/d (28 days study) and to 0, 10, 100 or 1000 mg/kg bw/d (90 days study). In both studies, an NOAEL of 1000 mg/kg bw was determined.
Repeated dose toxicity - dermal

A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure .
Repeated dose toxicity - inhalation

Testing is waived based on following justification: A key study is available for the oral route of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the inhalation route of exposure.

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
1 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

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

Repeated dose toxicity - oral

Two reliable repeated dose toxicity studies with the test substance are available, namely a 28 days and a 90 days study.

* 28 days repeated dose toxicity study:

Rats (5 per sex per dose) were exposed once daily to 0, 100, 500, 1000 mg test substance/kg bw/day for 28 consecutive days (Walz, 2011; Klimisch 2, equivalent to OECD guideline 407). The only statistically significant effects in absolute and relative female kidney weights could not be related to any macroscopic or microscopic findings or changes in clinical chemistry parameters. There is thus no indication of kidney toxicity. The NOAEL was therefore considered to be 1000 mg/kg bw/day.

*90 days repeated dose toxicity study:

Rats (10 per sex per dose) were exposed once daily to 0, 10, 100, 1000 mg test substance/kg bw/day for 90 consecutive days (Edwards, 2018; Klimisch 1, according to OECD guideline 408).

The oral administration of the test substance to rats by gavage did not result in any toxicologically significant effects for body weight development, food intake, clinical observations, hematological or blood chemistry parameters, or necropsy findings, at any dose level. The histopathological changes of increased rarefaction in the liver at 1000 mg/kg bw/day was considered to be non adverse, therefore the NOAEL for either sex can be considered to be 1000 mg/kg bw/day.

Repeated dose toxicity - dermal

No reliable data were available for this exposure route. This type of study does not need to be performed, since a 90 -day repeated dose toxicity study is available via oral route of administration (REACH Regulation, Annex IX, Column 2 adaptation). Moreover, the dermal route is not expected to be the main route of exposure.

Repeated dose toxicity - inhalation

No reliable data were available for this exposure route. This type of study does not need to be performed, since a 90 -day repeated dose toxicity study is available via oral route of administration (REACH Regulation, Annex IX, Column 2 adaptation). Moreover, the inhalation route is not expected to be the main route of exposure.

Justification for classification or non-classification

Based on the available data and according to the criteria of the CLP Regulation, the substance should not be classified for STOT repeated exposure via the oral route.