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EC number: 225-208-0 | CAS number: 4719-04-4
Based on the results of an open epicutaneus test in guinea pigs (BASF SE, 2002), supporting animal studies, and the evaluation of human data on skin sensitisation the test substance is considered to be sensitising to the skin.
In the pretest, a 15% test substance formulation (in aqua bidest) was found to be the minimum irritant concentration and the 4 % formulation the maximum non-irritant concentration. However, in the main test, 2 of 8 guinea pigs given 4 % test substance developed slight-moderate erythema and slight edema and scaling during the 3rd week of induction treatment. Thus, the maximum non-irritant concentration during induction was 0.4%.
Individual results obtained during the induction phase:
- 3 out of 8 animals treated with 15 % test substance solution exhibited very slight to well-defined erythema during the first week of induction. After the 6th induction until the 19th induction all animals showed very slight to well-defined skin reactions, partially in addition to scaling and superficial scabbing. - The 4 % concentration caused very slight to well-defined skin reactions and scaling in 2 out of 8 animals after the 12th induction until the 19th induction. - No signs of skin reactions during the induction phase were seen at the application sites of the 0.4 and 0.15 % test substance concentrations.
- After the first challenge with the 15 % test substance concentration very slight to moderate skin reactions were caused, partially in addition to scaling and superficial scabbing in all animals induced with 15 %, 4 % and 0.4 % and in 4 out of 8 animals induced with 0.15 %. At the second challenge, all animals induced with 4 %, 0.4 % and 0.15 % showed positive reactions, as well as 7 out of 8 animals induced with 15 %. - Challenge with 4% test substance concentration caused very slight to well-defined skin reactions in 4 out of 8 animals induced with 15 %, 4 % and 0.4 % and in 2 out of 8 animals induced with 0.15 %. At the second challenge, 6/8, 4/6, 4/5, 2/7 animals had positive reactions induced with 15 %, 4 %, 0.4 % and 0.15 %, respectively. - Challenge with 0.4 % test substance concentration did not cause any skin changes in all groups after the first challenge. However, after the second challenge 1 out of 8 animals induced with 0.4 % had a well-defined erythema. - Challenge with 0.15 % test substance concentration did not cause any skin changes neither after the first nor after the second challenge.
Under the experimental conditions of this study, the test substance was not sensitising in the Open Epicutaneous Test at challenge with concentrations of up to 0.4 % (max. non-irritant concentration) when induction was performed with concentrations lower than or equal to 4 %. The test substance was a skin sensitiser at 15 %.
The number of animals with skin findings after the 1st challenge and after the 2nd challenge.
(Test substance in aqua bidest.)
Control group 1*
Control group 2
Test group 4
Test group 5**
Test group 6***
Test group 7****
* 2 animals of control group 1 died 35 days after the beginning of the study.
** 2 animals of test group 5 died 34 days after the beginning of the study.
*** 3 animals of test group 6 died 32, 34 and 35 days after the beginning of the study.
**** 1 animal of test group 7 died 32 days after the beginning of the study.
Macroscopic examination revealed that the cause of deaths was not substance-related.
An open epicutaneous test in guinea pigs was identified as the key study (BASF SE, 1997). The test was performed in compliance with GLP based on the method of G. Klecak: Identification of Contact Allergens (Predictive Tests in Animals) in: Advances in Modern Toxicology Vol. 4, - Dermatotoxicology and Pharmacology - ed. F. N. Marzulli, H. I. Maibach - Pages 321 - 324 (1977).The open epicutaneous test investigated a range of concentrations during induction and challenge. The study concluded that HHT was not a sensitiser under specific test conditions. However the findings indicate that sensitisation potentially occurs when the specific conditions are exceeded.
It was concluded that the test substance was not sensitising at challenge with test substance concentrations of up to 0.4 % (max. non-irritant concentration) when induction was performed with concentrations lower than or equal to 4 %. However, the findings indicate that sensitisation potentially occurs when the specific conditions are exceeded (i.e.test substance was a skin sensitiser at 15 %). The skin sensitising potential of the test substance is supported by several reports on positive skin sensitisation reactions in humans after skin contact with the substance or products containing the substance (Schnuch et al., 1998; Roed-Petersen, 1977; de Groot et al., 1986; Dahl, 1981; Latorre et al. 2011). Taken together, the test substance is considered to be sensitising to the skin.
Supportingly, the substance was found to be a skin sensitiser in a murine local lymph node assay (L.A.C.S.A., 2015). In this study, an EC3 value could not be derived, since the S.I. values of the low and mid dose groups were above the threshold value of 3, and no conventional dose-response was observed. Further evidence for skin sensitising properties, including in humans, is available in public literature.
The Commission Working Group on the Classification and Labelling of Dangerous Substance, Meeting at ECB Ispra, 1997 (ECBI/32/97) agreed to maintain the skin sensitising classification and a 0.1 % concentration limit after evaluating both human and animal data relating to this test substance.
The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance needs to be classified as skin sensitisng cat. 1 (H317) under Regulation (EC) No 1272/2008, as amended for the ninth time in Regulation (EU) No 2016/1179.
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