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Toxicological information

Carcinogenicity

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Description of key information

Key value for chemical safety assessment

Additional information

In the chosen key studies, eqivalent to OECD TG 453 and according to GLP, Fischer 344 rats or B6C3F1 mice were fed diets with a microencapsulated preparation with a load of 31.9% citral for 104 -105 weeks (NTP 2003). Diet concentrations were 0 (vehicle control), 1000, 2000, or 4000 ppm for rats and 0 (vehicle control), 500, 1000, and 2000 ppm for mice. Daily dosages were 0, 50, 100, or 210 mg citral/kg bw/d for rats and 60, 120, and 260 mg citral/kg bw/d for mice.

In rats, there were no increased incidences of neoplastic findings attributable to the applied citral.

In mice,no citral related increased tumour incidences were observed in male animals. However, a positive trend in incidences of malignant lymphoma was observed in females, beeing significantly increased in the 260 mg/kg bw/d dose group versus the vehicle control group. Tissues most commonly affected were the spleen, mesenteric lymph nodes, thymus, and, to a lesser extent, the ovary. However, malignant lymphoma is a common spontaneous systemic neoplasm in B6C3F1 mice and the incidence in the concurrent vehicle control group was at the low end of the historical control ranges. Furthermore, the observed incidences in the citral treated groups were within the historical control ranges. Signs of general toxicity (see Section "Repeated dose toxicity") indicate that the minimal toxic dose (MTD) was reached for both species in these studies.

Under the conditions of this 2-year feed study, there was no evidence of carcinogenic activity of citral in male or female F344/N rats.

Under the conditions of this 2-year feeding study, there was no evidence of carcinogenic activity of citral in male B6C3F1 mice. Based on NTP criteria there was equivocal evidence of carcinogenic activity in female B6C3F1 mice based on increased incidences of malignant lymphomas.

Overall, no citral related increases in incidences of neoplastic findings were observed in rats and male mice. The species and gender dependent increase in the incidence of malignant lymphoma at a low level within the historical control ranges is not considered to provide sufficient evidence warranting the classification of citral as carcinogen.

Justification for classification or non-classification

The present data on carcinogenicity do not fulfill the criteria laid down in 67/548/EEC and CLP, and a non-classification is warranted.