Phosphoric acid, mono- and di-C16-18-alkyl esters

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

The skin sensitisation potential of Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters has been evaluated on the basis of a total of six Guinea pig maximisation test and one Buehler test using a weight of evidence approach. All available tests showed negative results. From the available date, the whole group of Phosphoric acid, alkyl esters was concluded to have no skin sensitisation potential in the conditions used in the studies.

Relevant, reliable and adequate data are available for the closely related C16 substances Hexadecyl dihydrogen phosphate, Potassium hexadecyl hydrogen phosphate and Dihexadecyl phosphate. Further supporting studies are available for C12 substances Phosphoric acid, dodecyl ester, potassium salt and Monolauryl phosphate and for Phosphoric acid, C9-15 branched and linear alkyl esters, potassium salts. Even if some of these studies have a restricted reliability, in a weight of evidence approach, the available information is considered adequate to allow a reliable risk assessment and classification and labelling.

A read across approach to Hexadecyl dihydrogen phosphate (Monopalmityl phosphate), Potassium hexadecyl hydrogen phosphate and Dihexadecyl phosphate is considered appropriate as the registered UVCB substance also consists of linear mono- and di-esters of Phosphoric acid with a mixture of C16 and C18 alkyl chains. The additional presence of C18 alkyl chains is not considered to influence the outcome of the sensitisation tests. Read-across to the C12 substances (Phosphoric acid, dodecyl ester, potassium salt; Monolauryl phosphate) is justified by a shorter chain length which usually leads to a higher irritation potential and better availability due to higher skin penetration and thus will be considered as a worst case. Negative sensitisation data on the Phosphoric acid, C9-15 branched and linear alkyl esters, potassium salts supports in addition that the whole substance group of Phosphoric acid, alkyl esters (and their salts) have no sensitisation potential.

For skin sensitisation, there is no reason to believe that results obtained with these read-across substances in guinea pigs would not be applicable to the substance to be registered.

In a dermal sensitisation study according to OECD guideline 406 with Hexadecyl dihydrogen phosphate (Monopalmityl phosphate), Dunkin-Hartley guinea pigs were tested using the method of Magnusson and Kligman. Positive control substance was formalin. For intradermal induction a concentration of 0.5% was used. The test concentration used for epicutaneous induction (40% in water) was not irritating. No SDS-pretreatment before epicutaneous induction was done. 24 hours after intradermal induction a 40% dilution of the test substance was applied and covered by occlusive dressing for 48 hours. Two test substance concentrations, 20% and 40% in water, were used for challenge (24 h, covered by occlusive dressing). Slight erythema (grade 1) was observed in both test and control animals after the first challenge, therefore a second challenge application was made one week later using lower concentrations (1% and 10% in water). After the second challenge application no visible changes of the treated skin sites (no erythema and no edema) were observed in test or control animals at any time point (24 h, 48 h, 72 h). In this study Hexadecyl dihydrogen phosphate (Monopalmityl phosphate) is not a dermal sensitiser.

In a dermal sensitisation study according to OECD TG 406 with Potassium hexadecyl hydrogen phosphate, Pirbright-Hartley guinea pigs were tested using the method of Buehler. Positive control substance was Alpha-hexylcinnamaldehyde (M&K test).

For epidermal induction a concentration of 100 % was used. The test concentration used for epicutaneous induction (100%) was not irritating. No pretreatment before epicutaneous induction was performed. Test substance concentration, used for challenge was 100% (6 h, covered by occlusive dressing). At challenge no visible changes of the treated skin sites (no erythema and no edema) were observed in test or control animals at any time point (24 h and 48 h after removal of the patches). In this study Potassium hexadecyl hydrogen phosphate is not a dermal sensitiser.

In a dermal sensitisation study according to OECD guideline 406 with Dihexadecyl phosphate, Dunkin-Hartley guinea pigs were tested using the method of Magnusson and Kligman. For intradermal induction a concentration of 2.5% in liquid paraffin was used. 24 hours after intradermal induction a 50% dilution of the test substance in liquid paraffin was applied and covered by occlusive dressing for 48 hours. Two test substance concentrations, 5% and 10%, were used for challenge (24 h, covered by occlusive dressing). Skin reactions were scored after 24, 48 and 72 h. One control animal died during the induction phase. The dermal response observed in the test animals was similar to that seen in the controls: Only slight localised erythema (grade 1, restricted to a small area of the challenge site) were observed in 2/14 control and 2/15 test animals after 24 h at 10% challenge concentration and in 1/15 test animals at 5%. After 48 and 72 h no dermal reactions were observed in the test group. 1/14 animals in the control group showed a slight localised erythema (grade 1, restricted to a small area of the challenge site) after 48 and 72 h. In this study Dihexadecyl phosphate is not a dermal sensitiser.

Skin sensitisation potential of Phosphoric acid, dodecyl ester, potassium salt was studied in female guinea pigs by the Maximisation test. The animals were induced by intradermal injection and topical application of the test article in the clipped shoulder region. No erythema nor edema was observed in the test article or vehicle control group by challenging with 3, 1, 0.3 and 0.1 % solution of the test article. From the results, Phosphoric acid, dodecyl ester, potassium salt was concluded to have no skin sensitisation potential in the conditions used in this study.

In a dermal sensitisation study according to OECD TG 406 with Monolauryl phosphate, Dunkin-Hartley guinea pigs were tested using the method of Magnusson and Kligman. Positive control substance was formalin. For intradermal induction a concentration of 0.25% was used. The test concentration used for epicutaneous induction (12.5%) was irritating. Thus, no pretreatment before epicutaneous induction was necessary. 24 hours after intradermal induction a 12.5% dilution of the test substance was applied and covered by occlusive dressing for 48 hours. Two test substance concentrations, 0.25% and 0.5%, were used for challenge (24 h, covered by occlusive dressing). At challenge no visible changes of the treated skin sites (no erythema and no edema) were observed in test or control animals at any time point (24 h, 48 h, 72 h after removal of the patches). In this study Monolauryl phosphate is not a dermal sensitiser.

Skin sensitisation potential of Phosphoric acid, C9-15 branched and linear alkyl esters, potassium salts (25%) solution (solvent purification) was studied in female guinea pigs by the Maximisation test. The animals were induced by intradermal injection and topical application of the test article in the clipped shoulder region. No erythema nor edema was observed in the test article or vehicle control group by challenging with 1.0 and 0.5 % solution of the test article. From the results, Phosphoric acid, C9-15 branched and linear alkyl esters, potassium salts was concluded to have no skin sensitisation potential in the conditions used in this study.

Skin sensitisation potential of Phosphoric acid, C9-15 branched and linear alkyl esters, potassium salts (25%) solution (liquid-liquid extraction) was studied in female guinea pigs by the Maxmization test. The animals were induced by intradermal injection and topical application of the test article in the clipped shoulder region. No erythema nor edema was observed in the test article or vehicle control group by challenging with 1.0 and 0.5 % solution of the test article. From the results, Phosphoric acid, C9-15 branched and linear alkyl esters, potassium salts (25%) solution (liquid-liquid extract) was concluded to have no skin sensitisation potential in the conditions used in this study.

As a conclusion, based on a weight of evidence approach, various structurally related PAE substances did not show any skin sensitising properties in guinea pigs. There is no information available for respiratory sensitisation. Therefore, there is a data gap in this respect. However, the data gap cannot be fulfilled with experimental data, since there is no internationally accepted animal model for respiratory sensitisation. In case human data for respiratory sensitisation emerges, this will be taken into account. For skin sensitisation, there is no reason to believe that results obtained with these read-across substances in guinea pigs would not be applicable to the substance to be registered. There is no reason to believe that results obtained in guinea pigs would not be applicable to humans.

Migrated from Short description of key information:
- Guinea pig maximisation tests: Not sensitising (OECD guideline 406, GLP), Induction: intradermal; Challenge: topical); read across substances:
Hexadecyl dihydrogen phosphate / Dihexadecyl hydrogen phosphate / Monolauryl phosphate / Potassium lauryl phosphate (Phosphoric acid, dodecyl ester, potassium salt)
- Guinea pig test (Buehler): Not sensitising (OECD guideline 406, GLP), Induction: epidermal; Challenge: topical); read across substance: Potassium hexadecyl hydrogen phosphate
- Guinea pig maximisation tests: Not sensitising (OECD guideline 406, no infomation on GLP), Induction: intradermal; Challenge: topical); read across substances: Phosphoric acid, C9-15-branched and linear alkyl esters, potassium salts (solvent purified) / Phosphoric acid, C9-15-branched and linear alkyl esters, potassium salts (liquid-liquid extract)

Justification for selection of skin sensitisation endpoint:
No single key study has been selected since all weight-of-evidence studies were negative.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on relevant, reliable and adequate data of read-across studies with chemically related substances, Phosphoric acid, mono- and di- C16-18 (even numbered) alkyl esters does not has to be classified and labelled according to the CLP Regulation (EC) No 1272/2008 and Directive 67/548/EEC with respect to skin sensitisation.