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Toxicological information

Carcinogenicity

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Description of key information

It should be noted that these studies are not required at the prescribed level of registration, and are included as supporting information only. Presence of three rare neoplasms in the respiratory tract of male rats along with preneoplastic lesions at the site of the tumors suggests carcinogenic potential of Allyl Glycidyl Ether (AGE). Though, the biological significance of these tumors could not be assessed due to the lack of historical control data, the results are enough to classify AGE as “suspected human carcinogen”.

Key value for chemical safety assessment

Carcinogenicity: via inhalation route

Endpoint conclusion
Dose descriptor:
NOAEC
23.3 mg/m³

Additional information

AGE was tested for its carcinogenic potential in 2 species (rats and mice; NTP, 1990).

Osborne-Mendel rats (50/sex/dose) were exposed to 0, 23.3 and 46.6 mg/m3 AGE vapors (6 hours/day, 5 days/week) for 103 weeks. Non-neoplastic lesions indicative of inflammation, degeneration and repair mechanisms were noted in both sexes in the olfactory and respiratory epithelium. In males at 46.6 mg/m3, 1 adenocarcinoma in the olfactory epithelium, 1 papillary adenoma and 1 squamous cell carcinoma in the respiratory epithelium were observed during histopathology examination. The fact that three different types of neoplasms originating from two different cell types without preneoplastic lesions were observed makes the treatment-relationship questionable. In addition, data interpretation was limited due to the absence of historical control data. Therefore, the carcinogenic potential in male rats was considered to be equivocal. No evidence of carcinogenic potential was found in females.

Similarly, B6C3F1 mice (50/sex/dose) were exposed to 0, 23.3 and 46.6 mg/m3 AGE vapors (6 hours/day, 5 days/week) for 102 weeks. Inflammation and degeneration of mucosa, olfactory and/or respiratory epithelium was observed. In three males and one female an adenoma of the respiratory epithelium was revealed at 46.6 mg/m3. Preneoplastic lesions were seen at the site of these adenomas. Although the incidence was not statistically significant, the rarity of these neoplasms in B6C3F1 mice suggests they were caused by AGE.

Taking data from both species into consideration, the biological significance of three neoplasms observed in the respiratory tract in male rats could not be assessed due to the lack of historical control data in this strain. The number of tumors in mice is limited, but the rarity of the neoplasms seen in this species and the presence of preneoplastic lesions at the site of the tumors suggests carcinogenic potential. While there is some uncertainty about the mechanism of tumor induction, it is likely that the genotoxic and irritant properties of this substance may play a role in tumourgenesis. Therefore, AGE is carcinogenic in rodents but the data does not support classification as a category 2 carcinogen. Thus, AGE should be classified in Cat 3/R40 based on EU standards and in Cat 2 based on GHS standards.


Carcinogenicity: via inhalation route (target organ): respiratory: nose

Justification for classification or non-classification

EU classification according to Annex VI of Directive 67/548/EEC: Cat 3/R40

CLP classification (EC No 1272/2008): Cat 2