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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
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Study performed according to OECD Guideline 407 and in compliance with GLP with Klimisch score 1.

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

In a repeated dose oral toxicity study conducted according to the OECD Guideline 407 and in compliance with GLP, the substance administered daily by oral gavage to rats in corn oil for 28 days entailed no mortality. Clinical observations were confined to increased salivation detected in animals of either sex treated with 325 and 1000 mg/kg bw/day throughout the treatment period. Isolated instances of noisy respiration and fur staining around the snout or mouth were also evident in 1-3 animals at 325 and 1000 mg/kg bw/day. No treatment-related changes were detected in functional performance and sensory reactivity. No adverse effects on bodyweight development and food consumption were detected for treated animals when compared to controls. Increased water consumption was detected in animals of either sex treated with 1000 mg/kg bw/day throughout the treatment period and in recovery males during the treatment-free period. No toxicologically significant changes were detected in the haematological, blood chemical and urinalysis parameters measured. Macroscopic examinations revealed a dark liver, evident in three males and two females at 1000 mg/kg bw/day. A statistically significant increase in liver weight, both absolute and relative to terminal bodyweight was evident in animals of either sex treated with 325 and 1000 mg/kg bw/day and in recovery animals following 14 days without treatment. Microscopic examinations of liver sections revealed hepatocellular hypertrophy in animals of either sex treated with 325 and 1000 mg/kg bw/day and in males treated with 35 mg/kg bw/day. Hepatocyte enlargement is commonly observed in the rodent liver following the administration of xenobiotics and, in the absence of associated inflammatory or degenerative changes, is generally considered to be adaptive in nature. Microscopic findings were also evident in the thyroid together with increased absolute and relative thyroid weights for females treated with 1000 mg/kg bw/day. Follicular cell hypertrophy was evident in animals of either sex from all treated groups. The liver and thyroid changes together with associated organ weight changes were considered to be adaptive in nature and do not represent an adverse effect of treatment. The microscopic kidney changes identified as increased severity of hyaline droplets in the proximal tubules of the kidneys were evident in males treated with 1000 mg/kg bw/day together with an increase in absolute and relative kidney weight. Accumulations of globular eosinophilic material in the tubular epithelium is a well documented effect, peculiar to the male rat. Female rats and other species do not develop nephropathy and for this reason, the effect is not indicative of a hazard to human health. The microscopic effects detected in non-recovery animals were observed to have generally or completely regressed among recovery high dose animals following 14 days without treatment.

Under the test conditions, the NOAEL was considered to be 1000 mg/kg bw/day in Wistar rats.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one study available.

Justification for classification or non-classification

The NOAEL identified in an oral 28-day repeated toxicity study was 1000 mg/kg bw/day. Therefore the substance is not classified according to Directive 67/548/EEC and CLP Regulation (EC) N° 1272 /2008.