Registration Dossier

Administrative data

Description of key information

PtBP did not produce skin reactions and did not demonstrate evidence of skin sensitization potential in guinea pigs.
Exposure to ptBC resulted in some positive cross-reactions upon challenge with ptBP.

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The skin sensitization potential of ptBP was assessed in guinea pigs of the Dunkin Hartley, Pirbright White strain (Krueger, 1998). The study was performed according to OECD Guidelines for the Testing of Chemicals No. 406 and in compliance with GLP, and therefore, was selected as the key study.  A preliminary study was conducted to determine the test concentrations to be used in the main study for the intracutaneous and dermal inductions. The highest non-irritant concentration also was determined for the challenge exposure. To this end, 2 animals were intracutaneously injected with 0.01, 0.05, 0.10, 0.50, 1.00, and 5.00% ptBP in corn oil. An additional 3 animals were dermally exposed to 0.2 g of each of 5, 10, 25, and 50% (w/w) ptBP test concentrations prepared in Vaseline. Each animal was exposed to two patches on each flank under occlusive conditions. Observations were performed 24 hours post-intracutaneous exposure and 48 and 72 hours post-dermal exposure using the grading scale by Magnusson and Kligman. To determine the highest non-irritating concentration of the test substance for the challenge exposure, animals were dermally exposed to 0.5, 1.0, 5.0, and 10.0% ptBP in Vaseline. Necrosis was observed 24 hours after intracutaneous exposure to 1.00 and 5.00% ptBP, 25 and 50% ptBP caused discrete to intense erythema and swelling combined with necrosis and eschar formation 48 and 72 hours after dermal exposure, and 5 and 10% ptBP caused discrete to moderate erythema 48 to 72 hours after the challenge exposure. Based on the results of the preliminary test, ptBP concentrations of 0.50% in corn oil, 10% ptBP in Vaseline, and 1.0 % in Vaseline were used in the main test for the intracuteneous induction, dermal induction, and challenge exposure, respectively.

In the main study, 10 animals comprised the ptBP test group and 5 animals comprised the vehicle control group. Skin reactions were observed and recorded 1 hour and 24 hours after intracutaneous induction, 49 and 72 hours after dermal induction, and 48 and 72 hours after the challenge exposure, all according to the grading scale by Magnusson and Kligman. Test and control animals displayed normal body weight gain throughout the investigation and no systemic effects were detected in treated animals during the observation period. At 1 hour and 24 hours after injection, all induction sites of test and control animals treated with Freund's complete adjuvant (FCA) showed intense erythema and swelling. Accompanying these observations were well defined pustulae at 1 hour and necrosis at 24 hours in all animals. In the absence of FCA treatment, all animals displayed moderate and confluent erythema, combined with well defined pustulae after 1 hour and discrete erythema after 24 hours of exposure. Following dermal induction, all test and control animals intracutaneously treated with FCA displayed erythema and swelling and eschar formations partially combined with bloody scratch wounds at 49 and72hours. No skin reactions, however, were observed in all other test and control animals at 49 and 72 hours following dermal induction. Challenge exposure also did not result in any skin reactions at 48 or 72 hours. Therefore, the results demonstrated that ptBP showed no evidence of contact skin sensitization in guinea pigs.

PtBP also was demonstrated to be not sensitizing in a study performed by Zimerson (1999) as cited in the EU Risk Assessment on ptBP. This study also was performed accordingto OECD Guidelines for the Testing of Chemicals No. 406, but was conducted in female guinea pigs of the Dunkin Hartley strain. The ptBP test group, vehicle control group, and positive control group were composed of 24, 12, and 6 animals, respectively. Briefly, the intradermal induction was carried out at a ptBP concentration of 1.0/0.67% w/v/mol x 1-1using a propylene glycol/actone (90/10 % v/v) solution as the vehicle. Topical sensitization was carried out at a ptBP concentration of 6.0/0.40% w/v/mol x 1-1. Additionally, all animals were dermally exposed to 10% w/v sodium lauryl sulphate (SDS) 24 hours prior to topical sensitization of the skin area. The challenge exposure was performed at a non-irritant concentration of ptBP of 2.0/0.13% w/v/mol x 1-1. Only 1 out of the 24 animals in the test group tested positive to ptBP. Therefore, ptBP was demonstrated to have very low sensitization capacity in this study. Alternatively, when p-ter-butylcatechol (ptBC) was used as the intradermal inducer (concentration of 3.40/0.20% w/v/vmol x 1-1in propylene glycol/acetone), 9 out of 24 animals reacted positively upon challenge with ptBP. Therefore, exposure to ptBC may lead to cross-reactions with ptBP.

Justification for classification or non-classification

The substance does not meet the criteria for classification and labelling for this endpoint, as set out in Regulation (EC) NO. 1272/2008.