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Carcinogenicity

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Description of key information

No studies are available for C12-18 AO. Two carcinogenicity studies are available for C12-14 AO, a two year oral feed study in rats and a 2 year dermal study in mice. The results of these studies can be read across to C12-18 AO on the basis of the substantial overlap in chain length distribution between the two substances and similarity in both local and systemic effects noted in oral and dermal studies. In the oral study there were no substance related macroscopic changes observed and no neoplastic or non-neoplastic treatment related effects were identified. In the dermal study no treatment related carcinogenic response was noted either dermally or systemically.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
One study available (K=2) performed using a method similar to OECD TG 451

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
One study available (K=2) performed using a method similar to OECD TG 451

Justification for classification or non-classification

In an oral carcinogenicity study in rats [International Research and Development Corporation (1983)] conducted in methods comparable to OECD TG 451, rats (Charles River CD) were fed diets containing 0.01, 0.1 and 0.2 % C12 -14 AO for up to 2 years. Based on findings, the NOAEL for systemic toxicity was 0.2 % in diet, equivalent to 90 mg AO/kg bw/day. There were no macroscopic changes observed and no neoplastic or non-neoplastic treatment related effects were identified.

In a dermal carcinogenicity study in mice [Hazelton Laboratories Inc. (1982)] conducted in methods comparable to OECD TG 451, C12 -14 AO was applied to the skin of mice (ICR Swiss mice, CD-1) at 0.05 %, 0.13 % and 0.26 %, 3 times/week for two years. A wide variety of spontaneous lesions, including neoplasms, were noted in the various tissues and were of the type and incidence commonly observed in mice of this age and strain. Substance related irritation was noted. The study did not result in any carcinogenic response in the exposed skin or systemically.

The results of these studies can be read across to C12-18 AO on the basis of the substantial overlap in chain length distribution between the two substances and similarity in both local and systemic effects noted in oral and dermal studies. On this basis C12 -18 should not be classified as carcinogenic.

Additional information

No studies are available for C12-18 AO. Two reliable animal studies are available for C12-14 AO. The results of these studies can be read across to C12-18 AO on the basis of the substantial overlap in chain length distribution between the two substances and similarity in both local and systemic effects noted in oral and dermal studies. In the key study [International Research and Development Corporation (1983)] which was conducted in methods comparable to OECD guideline 451 "Carcinogenicity Studies" groups of 60 male and 60 female rats (Charles River CD) were offered diets containing C12-14 AO at concentrations of 0.01, 0.1 and 0.2% for up to 2 years.Haematological, biochemical and urinalysis tests were conducted on all rats (pre-designated at study initiation) that were sacrificed at 52 weeks of study (10 males and 10 females). Haematological and biochemical tests were conducted for all surviving rats at study termination. No test substance-related trends in physical appearance and behaviour, survival or food (with compound) consumption were established. In treated males, dosage-related reductions were noted in body weights, whereas in females, significant reductions were only seen at the high dose level. The few haematological and biochemical values that reached statistically significant differences from the control values were not considered biologically meaningful. There were no notable features in the urinalysis results. There were no compound-related macroscopic changes observed among animals in this study. No neoplastic or non-neoplastic treatment related effects were identified. The NOAEL for the test substance was determined to be 0.2% in diet or 2000 mg AO/kg diet. Using a food consumption factor of 0.045kg diet/kg bw/day for rats, this translates into a dose of 90 mg AO/kg/day.

In the supporting study [Hazelton Laboratories Inc. (1982)] which was conducted in methods comparable to OECD guideline 451 "Carcinogenicity Studies" 0.1 ml of an aqueous solution of C12 -14 AO at 0.05%, 0.13%, and 0.26% (active ingredient) was applied to the dorsal skin of mice (ICR Swiss mice, CD-1), 3 times/week, for 2 years. Histopathology was performed on an extensive list of tissues from the control and high dose group and selected tissues from the mid and low dose groups which died or were sacrificed during the first year. At study completion tissues from all control and high dose mice were sectioned and examined. All tumours and selected tissues form the mid and low dose animals were also examined histologically.A wide variety of spontaneous disease lesions (including neoplasms) were noted in the various tissues examined and were of the type and incidence commonly observed in mice of this age and strain. Compound-related histomorphologic changes were observed in treated skin sections from male and female high dose mice. The epidermal responses consisting of diffuse acanthosis and hyperkeratosis were the result of test substance related irritation. The severity ranged from slight to moderately severe.The study did not result in any carcinogenic response on the exposed skin or systemically. Microscopic evaluation at the exposure site revealed compound-related dermal irritation in treated skin sections from the high-dose mice of both sexes. The epidermal response was characterized by acanthosis that increase in incidence and severity with dose. The NOEL for dermal carcinogenicity was determined to be the high dose of 0.26% test substance, which is equivalent to 2.6 mg/ml. 0.1ml of the 2.6 mg/ml dose solution was applied to mice three times per week (7 days), resulting in a total delivered dose of 0.111 mg/day. Using a default body weight for mice of 0.028 kg, results in an applied dose of 3.98 mg/kg/day.


Justification for selection of carcinogenicity via oral route endpoint:
Only study availlable

Justification for selection of carcinogenicity via dermal route endpoint:
Only study available (K=2)