Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin irritation:

In the key study, semiocclusive dermal administration of the test substance (approx. 95% retinyl palmitate) to New Zealand White Rabbits for 4 hours resulted in reversible erythema and no edema was observed (DSM 221051). The mean scores for erythema was 1.7 (24, 48 and 72 hours) for each animal. Reversible scaling was observed in 1 of 3 animals. Therefore, the test substance was found to be slightly irritating.

In the supportive study, occlusive dermal administration of the test substance in arachis oil (approx. 95% retinyl palmitate) to Vienna White rabbits for 4 hours resulted mostly in reversible erythema (1/6 animals showed slight erythema at the end of the observation period) and fully reversible edema (BASF 82/202-205). The mean scores for erythema and edema was 1.9 and 0.7 (24, 48 and 72 hours, all animals). Furthermore, desquamation was found in all animals at the 8 day reading. At control sites, only very slight skin irritation was observed with arachis oil DAB 8. Therefore, the test substance was found to be irritating on the basis of the scaling observed in all animals and the lack of reversibility for erythema in 1 of 6 animals. However, testing has not been performed according to current standart protocols (occlusive application, observation period 8 days).

Further evidences for dermal irritation is provided by structurally similar retinyl ester, i.e retinyl propionate and retinyl acetate:

In the key study for skin irritation performed according to GLP and OECD guideline 404, using New Zealand White Rabbits and retinyl propionate (purity approx. 90%), reversible erythema and edema was observed (DSM B-154`448). Individual erythema mean scores (24 -72 hrs) were >=2 (but <2.3 in 2/3 animals) and reversible desquamation or scabbing, epidermal lesions and scaling was observed in 3/3 animals. Therefore retinyl propionate was identified to be irritating to the skin.

In the key study for skin irritation according to GLP and OECD guideline 404, New Zealand White Rabbits were treated with retinyl acetate (1.5 mlU/g) (DSM 221040). The mean scores for erythema was 1.4 (24, 48 and 72 hours, 3 animals), and none of the animals showed a mean erythema score >=2. The erythema observed was fully reversible within 14 days and scaling was observed in 1/3 animals. None of the animals showed edema. Considering the given information on test substance concentration, i.e. 1.5 mlU/g, as 1500000 IU/g, a concentration of retinyl acetate in the tested substance is assumed to be 516 mg/g or approx 52%.

In the key study for skin irritation according to the OECD guideline 404 (deviation from current guideline: occlusive application, observation period), retinyl acetate (860 mg/g test substance or 86% in the test substance) induced mean scores for erythema of 2.3 and edema of 1.0 (24, 48 and 72 hours, 6 animals) in Vienna White rabbits (BASF 82/202-205). Erythema were found to be not fully reversible in 5/6 animals until the end of the observation period (8 days), whereas edema fully reversed within 8 days. Scaling was observed in 6/6 animals at the end of the study.

Althought the present key study on retinyl palmitate does not meet the criteria for classification as a skin irritant according to directive 67/548/EEC, the supportive study and the findings from structurally similar substances, i.e retinyl acetate and retinyl propionate, provide evidence for dermal irritative potential of this substance group, warranting a respective classification. However, the dermal irritative potential of retinyl palmitate appears to be lower than for retinyl acetate and retinyl propionate on the basis of the present data.

 

 

Eye irritation:

The key study for eye irritation was performed according to GLP and OECD guideline 405, using New Zealand White Rabbits and undiluted test substance (approx. 95% retinyl palmitate; DSM 221016). For eye irritation the mean irritation score (24 and 48 and 72 hrs) for conjuctival redness was 0.3, in 1/3 animals. No effects on corneal opacity, iris lesion or chemosis of the conjuctivae were noted. No adverse effects on the eye was noted after administration of the test substance when diluted (30%). The test substance was not an eye irritant under the conditions of the study.


Effects on skin irritation/corrosion: irritating

Justification for classification or non-classification

Skin irritation: The present data fulfill the criteria laid down in 67/548/EEC and a classification "irritating to skin" (R38) is warranted. According to regulation 1272/2008/EC, a non-classification is warranted. According to UN-GHS, the test substance needs to be classified "skin irritant" (category 3). Eye irritation: The present data on eye irritation do not fulfill the criteria laid down in 67/548/EEC and regulation 1272/2008/EC, and therefore, a non-classification is warranted.