Sulfonic acids, C14-16 (even numbered)-alkane hydroxy and C14-16 (even numbered)-alkene, sodium salts

Carcinogenicity

Description of key information

Carcinogenicity oral rats: NOAEL males ≥ 195 mg/kg bw/day, females ≥ 259 mg/kg bw/day females (highest applied dose), 2-year feeding

Carcinogenicity dermal mice: NOAEL ≥ 157.5 mg/kg bw/day (highest applied dose), 92 weeks

Carcinogenicity dermal rats: NOAEL ≥ 16.34 mg/kg bw/day (highest applied dose), 105 weeks

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

259 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

The available information comprises adequate and reliable (Klimisch score 2) data from a published study and peer-reviewed data from secondary literature. The selected study is thus considered sufficient to fulfil the standard information requirements set out in Annex X, 8.9.1 of Regulation (EC) No 1907/2006.

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

157.5 mg/kg bw/day

Study duration:

chronic

Species:

mouse

Quality of whole database:

The available information comprises reliable (Klimisch score 2), peer-reviewed data from secondary literature. The selected study is thus considered sufficient to fulfil the standard information requirements set out in Annex X, 8.9.1 of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The NOAEL for the test substance for carcinogenic effects was determined to be 259 mg/kg bw/day for the oral and 157.5 mg/kg bw/day for the dermal route. Sulfonic acids, C14-16 (even numbered)-alkane hydroxy and C14-16 (even numbered)-alkene, sodium salts does not have to be classified for carcinogenicity according to the criteria of EU Directive 67/548/EEC or Regulation (EC) No 1272/2008.

Additional information

Four carcinogenicity studies are available and demonstrate that Sulfonic acids, C14-16 (even numbered)-alkane hydroxy and C14-16 (even numbered)-alkene, sodium salts is not carcinogenic in rodents when administered either orally or percutaneously.

The key study is a 2-year feeding study in rats (Hunter & Benson, 1976). Doses of 39, 96, 195 mg/kg bw/day for male and 57, 132, 259 mg/kg bw/day for female rats were administered continuously in the diet. At the end of the treatment period no signs of carcinogenicity were found at gross necropsy and in histopathology, the NOAEL has been determined to be ≥ 195 mg/kg bw/day for males and ≥ 259 mg/kg bw/day for females. Further data on the oral route is available from a peer-reviewed 27-week feeding study in rats which also demonstrated no signs of carcinogenicity at the highest applied dose of 500 mg/kg bw/d (Ter Haar, 1983a; Smith, 1996).

Information on carcinogenicity via the dermal route is available from two further studies described in the review article by Ter Haar (1983a), the Little-report to 'The Soap and Detergent Association' (Little, 1993) and the IPCS report (Smith, 1996), one in rats and the other one in mice. The rats were treated twice weekly with a single dose corresponding to 105 mg/kg bw over a period of 105 weeks (Ter Haar, 1983a; Little, 1993). This was calculated to be a mean daily dose of 42 mg/kg bw/day (corresponding to 16.34 mg/kg bw/day a.i.). Results from gross and histopathology examinations revealed no carcinogenic effects at that dose. In the second study (Ter Haar, 1983a; Little, 1993; Smith, 1996) mice were treated over a period of 92 weeks three times a week with concentrations of each 20% and 25% of C14-18 and C14-16 AOS (Alpha sulfonic acids). These concentrations have been recalculated to mean daily doses of 126 and 157.5 mg/kg bw/day for C14-16 AOS. Again histopathology failed to demonstrate carcinogenicity for either sample or concentration of Sulfonic acids, C14-16 (even numbered)-alkane hydroxy and C14-16 (even numbered)-alkene, sodium salts. Therefore, the NOAEL was determined to be ≥ 157.5 mg/kg bw/day via the dermal route for mice.

However, toxikokinetic data has shown that absorption via the dermal route is negligible. Therefore, dermal exposure is of rather minor importance, although this is a relevant route of human exposure considering the uses of Sulfonic acids, C14-16 (even numbered)-alkane hydroxy and C14-16 (even numbered)-alkene, sodium salts.

Based on the lack of symptoms and histopathological findings one can assume that the actual NOAELs for oral and dermal exposure will be even higher, as these given here were only derived from the highest applied doses.

The available data confirmed the lack of carcinogenicity of the test substance.

Justification for selection of carcinogenicity via oral route endpoint:

Data is available from a published study and from secondary literature. The selected study provides the most adequate and reliable data based on the overall assessment of quality, and with special respect to duration.

Justification for selection of carcinogenicity via inhalation route endpoint:

The registered substance is most frequently marketed in aqueous formulation, and vapour pressure is negligibly low. Therefore, inhalation is not the most relevant route of exposure, and testing of carcinogenicity via the inhalation route can be omitted; in addition, data on carcinogenicity via the oral and dermal route are available.

Justification for selection of carcinogenicity via dermal route endpoint:

Two dermal studies are available from secondary literature; therefore, although the observed NOAELs are considered reliable and sufficient for hazard assessment, both studies suffer from limited documentation, and no key study is assigned. As no carcinogenic effects were observed in both studies, the selected one was considered to be most appropriate for assessment due to the higher dose level tested.