reaction mass of bis(2-propylheptyl) hexanedioate and O6-[2,2-bis[[6-oxo-6-(2-propylheptoxy)hexanoyl]oxymethyl]butyl] O1-(2-propylheptyl) hexanedioate

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Due to a lack of experiments with the test substance and the existence of a structural analog (read-across substance) part of or the complete data was derived from the read-across substance. For details on the read-across reliability please refer to IUCLID Section 13. 

The read-across substance Bis(2-propylheptyl) hexanedioate was assessed for its skin sensitising potential using the Local Lymph Node Assay (LLNA) in mice. The read-across substance solutions at different concentrations (10, 25, and 50 % (w/w)) were prepared in the vehicle acetone:olive oil (4+1, v/v). The highest concentration tested was the highest concentration that could be achieved whilst avoiding systemic toxicity and excessive local skin irritation (as determined by a pre-experiment). A statistically significant or biologically relevant increase in ear weights was not observed in any treated group in comparison to the vehicle control group. Furthermore, for BALB/c mice, a cutoff-value of 1.1 for the ear weight index was reported for a positive response regarding ear skin irritation. The index of 1.12 determined for the high dose group reached this threshold, indicating a marginal borderline positive response for ear skin irritation. But the index obtained did not exceed the threshold of 1.25 for excessive irritation stated in the OECD. A test item is regarded as a sensitiser in the LLNA if exposure to one or more test item concentration results in a 3-fold or greater increase in the Stimulation Index (S.I.). In this study an S.I. of 3.70 were determined with the read-across substance at concentrations of 50 %. Furthermore, the cutoff-value of 1.55 for a positive response regarding the lymph node cell count index reported for BALB/c mice was exceeded in the high dose group and the read-across substance was found to be a weak skin sensitizer and an EC3 value of 39.2 %(w/w) was derived (BASF SE 2013).

The LLNA was shown to overestimate the skin sensitizing potential of some long-chain carbonic acids and their esters as well as fatty alcohols (Kreiling et al., Food and Chemical Toxicology 46 (2008) 1896 -1904; Anderson et al., J Allergy 2011, Article ID 424203; Basketter et al., Contact Dermatitis 60 (2009) 2:65 -69) possessing molecular structures similar to the read-across substance.

Thus, the dermal sensitizing potential of the read-across substance Bis(2-propylheptyl) hexanedioate was investigated according to the methods of the OECD guideline 406 (1992) in a guinea pig maximization test (GPMT) by MAGNUSSON and KLIGMAN (1970). Two main studies were performed with 5 animals per control group and 10 animals per test group. The test concentrations for the first main study were selected on the basis of the results of the preliminary investigations regarding dermal exposure and intradermal injection. Two main studies were conducted with an intradermal induction with 5 % of the read-across substance in olive oil (day 0) followed by a dermal induction with the undiluted substance (day 7). In the first main study a dermal challenge (day 21) was performed with the undiluted read-across substance and a rechallenge (day 28) with 75 % of the read-across substance in olive oil while for the second main study a challenge with 75 % and rechallenge with 50 % of the test item in olive oil were used. During the two main studies, animals of both the control groups and the test groups responded with slight skin reactions to the treatment with the 75 % or 100 % read-across substance. These findings were confirmed by the rechallenges. Since the incidence and severity of the skin reactions in the control and the test groups were comparable in the first main study while the incidence of skin reactions was even higher in the control than in the treated animals during the second main study, the read-across substance was sufficiently shown not to be a skin sensitizer (BASF SE 2014).

Migrated from Short description of key information:
The read-across substance was weakly sensitizing in the mouse local lymph node assay but not sensitizing in the guinea pig maximization test verified by a second main study and a rechallenge. Therefore it was concluded to be not sensitizing.

Justification for selection of skin sensitisation endpoint:
GLP guideline study with a read-across substance supported by further studies

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available data, the read-across substance does not have to be classified for skin sensitisation according to Regulation (EC) No 1272/2008 (CLP/GHS) as amended for the seventh time in Regulation (EC) No 2015/1221.