(2E)-2-methyl-3-phenylacrylaldehyde

Carcinogenicity

Description of key information

In a peer reviewed published 3 month and 2 year repeated dose oral study, trans-cinnamaldehyde did not cause cancer in male or female rats 
For the 2-year rat study the NOEL obtained was 50 mg/Kg bw/day and the NOAEL (carcinogenicity) was 200 mg/Kg bw/day. 

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

200 mg/kg bw/day

Study duration:

chronic

Species:

rat

Quality of whole database:

Good selected study in Klimisch score 1

Carcinogenicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Carcinogenicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

In a key read across 2-year study (NTP, 2004) undertaken to evaluate the carcinogenic potential of the test material (trans-cinnamaldehyde; CAS# 14371-10-9), groups of 50 male and 50 female F344/N rats were fed diets containing 1,000, 2,100, or 4,100 ppm (equivalent to 50, 100, and 200 mg/Kg bw/day, respectively) microencapsulated trans-cinnamaldehyde for 2 years. Additional groups of 50 male and 50 female rats received untreated feed (untreated controls) or feed containing placebo microcapsules (vehicle controls).

 

All animals were observed twice daily. Body weights were recorded initially, on day 8, every 4 weeks thereafter, and at the end of the studies. Clinical findings were recorded on day 36, every 4 weeks thereafter, and at the end of the studies. Complete necropsies and microscopic examinations were performed on all rats and mice. At necropsy, all organs and tissues were examined for grossly visible lesions, and all major tissues were fixed and preserved in 10% neutral buffered formalin, processed and trimmed, embedded in paraffin, sectioned to a thickness of 4 to 6 µm, and stained with hematoxylin and eosin for microscopic examination. For all paired organs (e.g., adrenal gland, kidney, ovary), samples from each organ were examined.

 

Ten male and ten female rats from each group were randomly selected for urinary metabolite analysis at 2 weeks and 3, 12, and 18 months. Animals were placed in metabolism cages for 24 hours. Urine samples were placed on ice, urine volume and creatinine concentration were measured, and then the samples were frozen pending shipment to the laboratory for hippuric acid quantitation.

 

Survival of 4,100 ppm males was greater than that of the vehicle controls. Mean body weights of 4,100 ppm males and females were generally less than those of the vehicle controls throughout the study. Feed consumption by 2,100 and 4,100 ppm males and 4,100 ppm females was less than that by the vehicle controls at the beginning and end of the study. Urinary hippuric acid served as a good biomarker for trans-cinnamaldehyde exposure in rats. In most cases, the hippuric acid to creatinine ratio was proportional to dose, indicating that absorption, metabolism, and excretion processes were not saturated. In the study, the ratio tended to decrease with time and was well correlated with the calculated trans-cinnamaldehyde doses at similar times

 

There were no neoplasms or non-neoplastic lesions that were attributed to exposure to trans-cinnamaldehyde.

 

Based on the results observed, the NOAEL for carcinogenicity was determined to be 4100 ppm (equivalent to 200 mg/Kg bw/day).

In a supporting read across peer reviewed published report (Stoner et al., 1973), a 24 week screening study to assess the carcinogenicity of cinnalmaldehyde on mice achieved a NOEL of 800 mg/Kg bw/day.

Justification for classification or non-classification

Based on read across data available from trans-cinnamaldehyde, alpha methylcinnamaldehyde does not meet the criteria to be classified for carcinogenicity under EU CLP.