(xylenes and 4-ethylbenzene)sulfonic acids

Carcinogenicity

Description of key information

There are no carcinogenicity studies for the aromatic sulphonic acids. These substances are very corrosive as was demonstrated in skin and eye irritation studies, in the acute oral studies, and in the single repeated dose oral study. Two-year exposures to corrosive substances are not recommend.

There are two key studies for the hydrotrope category substances, both conducted on sodium xylene sulphonate (SXS). The key studies are 2-year rat and mouse dermal exposure studies conducted under GLP.  Up to 240 mg (rats) and 727 mg (mice) sodium xylenesulfonate/kg body weight in 50% ethanol were dosed 5 days per week for 104 weeks. There were no treatment related incidences of mononuclear cell leukaemia, neoplasms, or non-neoplastic lesions of the skin and other organs. The increased incidence of epidermal hyperplasia may have been related to exposure to the test substance. The NOAEL for systemic toxicity and carcinogenicity was reported as 240 mg/kg bw/day for rats and 727 mg/kg bw/day for mice. The NOAEL for local effects is considered to be 60 mg/kg bw/day, based on the findings from the rat study.

 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no study available

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

240 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Sufficient to meet requirements.

System:

other: skin

Justification for classification or non-classification

There was no evidence of carcinogenic activity in two dermal carcinogenicity studies in rats and mice. Therefore there is no justification for hazard classification.

Additional information

There are two chronic studies for the related hydrotrope substances. Hydrotropes are the salt form of the sulphonic acids and therefore are used as read-across for this endpoint. The two hydrotrope studies are 2-year rat and mouse dermal exposure studies conducted under GLP. Up to 240 mg (rats) and 727 mg (mice) sodium xylenesulfonate/kg body weight in 50% ethanol were dosed 5 days per week for 104 weeks. There were no treatment related incidences of mononuclear cell leukenia, neoplasms, or nonneoplatic lesions of the skin and other organs. The increased incidence of epidermal hyperplasia may have been related to exposure to the test substance. The NOAEL was reported as 240 mg/kg bw/day for rats and 727 mg/kg bw/day for mice.

Hydrotrope Studies

50 male and 50 female rats and mice were administered dermal applications of up to 240 mg (rats) and 727 mg (mice) sodium xylenefulfonate/kg body weight in 50% ethanol. Doses were applied 5 days per week for 104 weeks to the clipped interscapular skin at volumes adjusted for the weights of the animals throughout the study. Animals were housed individually and fed and given water ad libitum. Cages were changed weekly and racks were rotated every 2 weeks. All animals were observed twice daily and clinical findings were recorded monthly. Body weights were recorded weekly for 13 weeks, then monthly thereafter. All animals were necropsied and a complete histopathological examination was performed. All organs and tissues including skin were examined for grossly visible lesions. Major tissues were examined microscopically and slides were evaluated by an independent quality laboratory in addition to the study laboratory pathologist. The study was conducted under GLPs from late 1990 to late 1992 at the Battelle Columbus Laboratories. NTP Technical Report on the Toxicology and Carcinogenesis Studies of Technical Grade Sodium Xylenesulfonate in F344/N Rats and B6C3F1 Mice. NTP TR 464, June 1998. The study reliability is Klimisch 1.

Survival of the dosed males and females was similar to that of the control groups and consistent with historical controls.

Mean body weights of dosed males and females were similar to those of the controls throughout and there were no clinical findings considered treatment related in males. In female rats, clinical findings were limited to irritation at the site of application in one control, in 4 at 120 mg/kg bw and in 2 at 240 mg/kg bw. In mice, clinical finding were limited to irritation of the site of application in female conrols, and males and females at the 364 and 727 mg/kg bw doses. There were no treatment related incidences of mononuclear cell leukenia, neoplasms, or nonneoplatic lesions of the skin and other organs. The increased incidence of epidermal hyperplasia may have been related to exposure to the test substance.