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Description of key information

The key study was the limit oral acute study (similar to OECD guideline 401) in rats with retinyl proprionate, resulting in an LD50 > 2000 mg/kg. 

Key value for chemical safety assessment

Additional information

In the chosen key study similar to OECD 401 guideline retinyl propionate (approx. 95% purity) was administered in olive oil via gavage at a dose of 2000 mg/kg bw to Wistar rats (BASF 10A0454/891109). No deaths, clinical signs of toxicity or pathological findings were noted. Consequently, the oral LD50 was > 2000 mg/kg bw in rats.

In a supportive study similar to OECD 401, oral administration via gavage of 2425, 3434 or 4850 mg/kg retinyl palmitate in peanut oil resulted in mortality, body weight loss an clinical effects, i.e. ataxia, piloerection, respiratory depression, hypomotility (DSM 1532). An LD50 = 2300 (1660 - 3200) mg/kg bw has been determined.

Similar acute toxicity has been observed in mice after oral (gavage) application of 1717, 2425, 3434 or 4850 mg/kg bw retinyl palmitate in peanut oil, resulting in mortality, body weight loss, and clinical effects, i.e. ataxia, piloerection, respiratory depression, hypomotility (DSM 1533). A lower LD50 = 1275 (385-4200) mg/kg has been determined, fulfilling the criteria according to 67/548/EEC and 1272/2008/EEC. However,

a higher variability of this value is evident compared to the LD50 value obtained in the rat study. Furthermore, mortality observed at doses close to the limit dose of 2000 mg/kg ranged from 40% to 90% for the dose group 1717 and 2525 mg/kg respectively.

Overall, on the basis of the present data, the acute toxicity of retinyl propionate is low, and the LD50 values obtained in the key and supportive study in rats represent a valid justification for the non-classification as acute oral toxicant under the criteria laid down under 67/548/EEC and 1272/2008/EEC.

Justification for classification or non-classification

The present data on acute oral toxicity do not fulfill the criteria laid down in 67/548/EEC and 1272/2008/EEC, and therefore, a non-classification is warranted. According to UN-GHS, the test substance needs to be classified as acute oral toxicant (Category 5).