Fatty acids, C16-18 and C18-unsatd., Me esters, epoxidized

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Buehler (CAS 158318-67-3)

The dermal sensitizing potential of the test substance was investigated by means of the Buehler test according to OECD 406.

The main study was performed on 30 guinea pigs in total arranged in a control group of 10 and a test group of 20 animals. The test concentrations for the main study were selected based on the results of a pre­limi­nary investigation. Since none of the pre-test animals responded with skin reactions to the single treatment with the test item in concentrations of 25 %, 50 %, 75 % and 100 % (w/w) in the vehicle polyethylene glycol (PEG), the undiluted test item was determined to be used in both the induction phase and challenge phase. The main study started with an induction phase including an occlusive patch topical appli­cation for 6 hours once a week for three consecutive weeks. The animals of the test group were induced twice with the 100 % (w/w) test item, whereas the animals of the control group were induced with the vehicle polyethylene glycol. Due to occurrence of skin reactions with increasing intensity (grade 1 in 3/20 test group animals after 1^st induction; grade 1 in 7/20 and grade 2 in 12/20 test group animals after 2^nd induction), a reduction of test item concentration to 75 % (w/w) was determined for both the third induction treatment as well as the challenge treatment. In addition, for the third induction the application area was moved to untreated skin. Erythema of grade 1 was observed in 4/20 test group animals after 3^rd induction with the 75 % (w/w) test item, whereas 10/20 test group animals displayed erythema of grade 2 and 6/20 test group animals even grade 3 erythema. During the induction phase, none of the ten control group animals displayed any skin reactions. Four weeks after the first induction, the 6-hour challenge procedure was conducted with an occlusive topical application of the test item on the right cranial flank of all animals in a concentration of 75%. A vehicle exposure took place on the right caudal flank. The skin reactions were evaluated 24 hours and 48 hours after the challenge application.

All animals of the test group (20/20; 100 %) and all animals of the control group (10/10; 100 %) responded with skin reactions to the challenge treatment with the test item in differing intensities. Erythema formation was assessed with grade 1 (7/10) and grade 2 (3/10) in the control group. On the contrary, distinct reaction including even grade-3-erythema (15/20) were observed in the test group among mild to moderate erythema ranging between grades 1 and 2 (5/20) 24 and 48 hours after removal of the patches. Due to these ambiguous findings providing indications for both irritating effects as well as a sensitizing poten­tial of the test item, a re-challenge was performed using the same animals (test item concentration of 50 % w/w). One week after the challenge, the 6-hour re-challenge procedure was conducted with an occlusive topical application of the test item on the left cranial flank of all animals. A vehicle exposure took place on the left caudal flank. The skin reactions were evaluated 24 hours and 48 hours after re-challenge application. Again, all animals of the control group and all animals of the test group responded with skin reactions to the re-challenge treatment with the test item. Control animals displayed mild to moderate erythema (grade 1 and 2), whereas moderate to severe erythema (grade 2 and 3) were observed in the half of test group animals. In both challenge experiments, stronger reactions in the test group than in the control group were observed, which may be considered as a hint for a skin sensitizing potential of the test item. However, since all animals of all groups showed a skin reaction, a delayed contact sensitization in the guinea pig can be neither excluded nor con­cluded based on the results of that study. Furthermore, the observed skin reactions in all animals of the control group give also evidence of an irritation potential of the chosen concentration.

Based on these inconclusive results of the non-adjuvant sensitization study described in this final report, the test item cannot be classified unambiguously as skin sensi­tizer or non-sensitizer. Therefore, a second Buehler test with an extended pre-test was started with the test substance. This study is still ongoing.

Buehler test (CAS# 97553-05-4)

For CAS# 97553-05-4 a GLP guideline study according to OECD TG 406 was performed with Pirbright White guinea pigs (10 animals per dose group) to assess the skin sensitising potential of the test substance (Henkel, 1993). After a weekly epidermal induction (0.5 mL of a 25% test substance solution), which was performed thrice, a epidermal challenge procedure was performed with 10% test substance solution, which was supposed to be a non-irritating concentration regarding the results obtained from the dose finding study, which was performed prior to the main study. While 10/10 animals of the negative control group showed a slight reaction, 8/10 animals of the test group showed a slight reaction after 24 h of the challenge procedure. These findings were also present after 48 h, when 10/10 control animals and 5/10 test animals still showed a slight reaction to the challenge. Because of the high number of positive responses in the control group, the data are judged to be inconclusive and insufficient for classification purposes (Henkel 1993).

GPMT (CAS# 8013-07-8)

For CAS# 8013-07-8 a non-GLP study silimar to OECD TG 406 was performed with Pirbright White guinea pigs (10 animals per dose group) to assess the skin sensitising potential of the test substance. Under the experimental conditions employed, no differences between the test group and the vehicle-treated controls were seen. after either intradermal or epidermal challenge application of the test item. The test item was found to be devoid of skin-sensitizing (contact allergenic) potential in albino guinea pigs.

 

 

 

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data on skin sensitization is not consistent. Based on these inconclusive results of the non-adjuvant sensitization study, the substance should be classified for precautionary reasons, as Skin Sens.1B, H317: May cause an allergic skin reaction in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008.