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Toxicological information

Carcinogenicity

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Description of key information

Carcinogenesis bioassay, administration in the diet (similar to OECD TG 451):
- F344 rats: carcinogenic for males (inducing neoplastic nodules in the liver and transitional-cell carcinomas in the urinary bladder); not carcinogenic for female.
- B6C3F1 mice: no clear evidence of carcinogenicity in mice of either sex.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
chronic

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Two studies are reported for this endpoint. Both are carcinogenesis bioassay performed by the NTP. They were identified as suitable and reliable for this endpoint. 11 -aminoundecanoic acid was tested for carcinogenicity in mice and rats by administration in the diet for 103 and 104 weeks, respectively, at 7500 and 15000 ppm.

In the rat carcinogenicity study, increased incidence of transitional-cell carcinomas of the urinary bladder ( 15000 ppm) and neoplastic nodules of the liver (7500 and 15000) were observed in male rats. Epithelial hyperplasia of the urinary bladder and renal pelvis were observed in both sexes in rats. The neoplastic nodules of the liver observed in Fisher males rats were considered as benign tumours very common in this specific strain and sex and remain within the overall historical variations. The increased incidence of transition-cell carcinoma of the urinary bladder occurred only in the higher dose-group and in males only and were always associated with hyperplasia of the urinary bladder epithelium (non neoplastic lesions).

Although, the mechanism for development of these tumors is unknown, it can be hypothesized that the transitional-cell carcinoma found in male fisher rats were an indirect consequence of the non neoplastic local effect induced by 11-aminoundecanoic acid when very high dose-levels are repeatedly ingested by the rats, exceeding the threshold level of 7500 ppm in the diet, every day during almost their whole life.

 

In the mouse carcinogenicity study,. The increase of malignant lymphoma in male mice was statistically significant only at the low dose (7500 ppm) but not at the high dose (15000 ppm) and occurred in male mice only. Furthermore, malignant lymphomas were among the most common tumours and the observed incidence in the NTP bioassay remain within the overall historical variations. No clear evidence was found for the carcinogenicity of 11-aminoundecanoic acid in B6C3F1 mice of either sex.

 

Conclusion:

11-aminoundecanoic acid was tested for carcinogenicity in mice and rats by administration in the diet at 7500 and 15000 ppm. An increased incidence of transitional-cell carcinomas of the urinary bladder and neoplastic nodules of the liver were observed in male rats only. No clear evidence for an increased incidence of treatment related tumours was seen in mice. The overall interpretation of the results provided by a battery of in vitro and in vivo short term genotoxicity test is that 11-aminoundecanoic acid has no genotoxic potential. Consequently, the excess of malignant tumours of the urinary tract found in males are believed to have occurred through a non genotoxic mechanism and to be associated with the hyperplasia which were induced when the dose of 11- aminoundecanoic acid reached a sufficiently quite high level. Furthermore, extrapolation of these effects to human would not be relevant taking into account the use of 11-aminundecanoic in closed system which was confirmed by the very low worker exposure (cf. monitoring study in Arkema plant chapter 7.2).

IARC categorized 11-aminoundecanoic acid as “non classifiable as to it carcinogenicity to humans (category 3) due to the limited evidence provided by the animal database and the absence of epidemiological data (IARC, 1986)

Justification for classification or non-classification

No-classification is warranted for carcinogenicity for the following reasons:

- Very limited evidence provided by the animal data and the absence of epidemiological data in humans,

- Carcinogenic effects were observed only in one sex and one species,

-11-aminoundecanoic acid has no genotoxic potential as shown by the extensive battery testing,

- The available information from carcinogenicity studies indicates that the non genotoxic mechanism of action (also demonstrated in the DNA binding study (Bolt 1987)) were observed at very high dosage and were the consequence of a non oncongenic local irritant effect due to repeated exposure to rats, daily during almost their whole life,

- Under these experimental conditions, the low carcinogenic potential is considered as not extrapolable to human,

- IARC categorized 11-aminoundecanoic acid as “non classifiable as to it carcinogenicity to humans (category 3) due to the limited evidence provided by the animal database and the absence of epidemiological data (IARC, 1986).