Due to the carcinogenic effect of methyl eugenol, SCCNFP has established a limit for content of methyl eugenol in leave-on cosmetic products of 0.0002 weight% (5, 36). For 2 of the 3 products analysed for Methyl eugenol, the content was above the detection limit of 0.0012 and 0.0036 weight%, respectively. This means that both products (no. 80 and 93) are above the legislative maximum limit for methyl eugenol in leave-on products. Therefore, the content of methyl eugenol may pose a potential health risk when using the products in question.
Table 9.2 gives an overview of the results of the worst case calculations of the oral and dermal exposure using EUSES. EUSES is a data base programme used for exposure calculations. Summaries of the exposure data can be seen in table 8.1. The modelling results are supplemented by manual calculations for all 26 fragrances + Methyl eugenol, cf. table 9.2.
No data has been found on inhalation of methyl eugenol.
In order to minimize the availability of products to consumers at concentrations of concern, the notification threshold for the manufacturing of consumer products containing these substances is proposed to be aligned with the safety data sheet (SDS) disclosure concentration threshold. For most substances, these concentration thresholds are set at either ≥0.1% or ≥1.0%, depending on the hazard class. In the case of methyl eugenol, the proposed concentration threshold is ≥0.0002% to align with the limit set by the Pest Management Regulatory Agency for methyl eugenol in pest control products applied to the skin and with Health Canada’s Cosmetic Ingredient Hotlist entry that describes a limit of 0.0002% for methyl eugenol in other leave-on and oral hygiene products.
Methyl eugenol is not mutagenic in Ames test at the highest test concentration of 0.33 mg/plate. The substance has shown that it may introduce sister chromatide exchange in Chinese hamster ovary cells with activation, but it did not introduce chromosome changes in Chinese hamster ovary cells with and without activation. 14-week in vivo micronucleus tests with blood cells in mice were negative.
Benzoic acid, 4-hydroxy-, phenylmethyl ester
Tests have been carried out with oral exposure of rats in doses of 0, 10, 30, 100, 300 and 1000 mg/kg bw, 5 days/week for 14 weeks. At an exposure of 100 mg/kg bw/d, effects such as increased liver weight in male animals and enzyme changes and liver cell damage in both sexes were observed. Furthermore, at a dose of 300 mg/kg bw/d, reduced body weight, increased bile amount, inflammation of the mucous membrane of the stomach was seen in both sexes along with an increased liver weight in females. Exposure to 1000 mg/kg bw/d furthermore lead to an increased testicular weight (35). The same tests on mice showed the same type of effects (35). NOEL for methyl eugenol has been set at 10 mg/kg bw/d for both species with effects on the liver and not cancer as the critical effect (37).
Benzoic acid, 4-hydroxy-, butyl ester
Methyl eugenol has been tested by NTP (National Toxicology Programme) for toxicity and carcinogenicity based on the structural similarity with safrol (CAS No. 94-59-7) which is a known carcinogen (35). These tests have been reported below: