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Administrative data

Description of key information

90-day repeated dose toxicity (subchronic) study according to OECD TG 408: NOAEL is determined at 15,000 ppm, equivalent to 1248.8 mg/kg bw/day in males and 1452.1 mg/kg bw/day in females.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
1 249 mg/kg bw/day

Additional information

In the key study, a subchronic toxicity study (BASFAG50S0408/99093) according to OECD TG 408, the test substance Uvinul A Plus was administered to 10 Wistar rats per dose per sex in diet at dose levels of 0 ppm, 600 ppm (in males approx. 51.7 mg/kg bw/day; females: approx. 59.3 mg/kg bw/d), 3000 ppm (in males: approx 250.2 mg/kg bw/d; females: approx 288.0 mg/kg bw/d), 15000 ppm (in males: 1249 mg/kg bw/day; females: approx 1452 mg/kg bw/d) for three months.

No compound related effects in mortality, clinical signs, body weight, food consumption, hematology and clinical chemistry were observed.  The distinct clinical findings in one high-dose male which was sacrificed moribund on day 49 were also spontaneous in nature.

No substance related neurobehavioural, ophtalmoscopic effects or effects on sperm parameters were observed.

All gross lesions and microscopic findings recorded were either single observations or they occurred in control animals only, or they were recorded at low or comparable incidence and graded severity in control and high dose males and/or females. Hence, they were all regarded to have developed fortuitously and unrelated to treatment.

The mean relative weights of testes (+9%, high dose group) and heart (female, low dose group +15%) were significantly increased, whereas the mean relative weight of the spleen (mid dose group in females) was significantly decreased (-31%). However, these findings were determined to be not treatment-related as,

- the absolute testes and heart weights were not significantly changed,

- all gross lesions and microscopic findings recorded were either single observations, or occurred in control animals and no dose-response relationship was evident,

- comprehensive examinations of reproductive organs as well as sperm analysis did not give any indication for an impairment of fertility which support a substance related effect. In addition no effects on fertility parameters were noted in the 2-generation study.

The mean relative liver weights in male (+7%) and female rats (+10%) in the high dose group were statistically significantly increased. However the following points support the assumption that the increase in the relative liver weight is rather an incidental observation:

- lack of any morphological changes (gross pathology (lesions) and microscopic findings),

- no significant difference in results of blood chemistry concerning liver related enzymes (aminotransferases and alkaline phosphatases) between the control and the treated groups,

- the absolute liver weights were not significantly altered.

In addition the terminal body weight was slightly although not significantly decreased in both males (-3.6%) and females (-2.5%) of the high dose group. Therefore, the small decrease in body weights effected the statistically significant increase in the liver weights in this group.

Based on the obtained study results and their interpretation, the no observed effect level (NOAEL) under the conditions of the study was therefore 15000 ppm (equal to 1248.8 mg/kg bw/day in males or 1452.1 mg/kg bw/d in females).

Justification for classification or non-classification

The present data on repeated dose toxicity do not fulfill the criteria laid down in 67/548/EEC and 1272/2008/EEC, and therefore, a non-classification is warranted.