Why doesn't Typology use 4-methylbenzylidene camphor?

Enzacamene is among the UV filters authorised in the European Union. Therefore, it is listed in Annex IV of Regulation (EC) No 1223/2009. The use of 4-MBC in European skincare products is permitted up to a maximum concentration of 4%. However, this sunscreen filter is prohibited in the United States, Japan, and Denmark.

Today, even when its concentration is less than 4%, the Scientific Committee for Consumer Safety (SCCS) cannot conclude on the safety of 4-MBC, as the information provided is insufficient to fully assess its potential genotoxicity.

Enzacamene, a genotoxic compound?

A recent study submitted in March 2022 assessed the mutagenic potential of 4-methylbenzylidene camphor in accordance with OECD TG 476 guidelines, using V79 hamster cells. The aim was to detect genetic mutations induced in mammalian cells in vitro. The cells were exposed for four hours to different concentrations of 4-MBC, with or without metabolic activation. Without metabolic activation, severe cytotoxicity was observed from 8 µg/mL, which limited the analysis to lower concentrations. With metabolic activation, cytotoxicity occurred at 100 µg/mL. At all the doses studied, no significant increase in the number of mutant colonies per million cells was observed. Only a slight rise in the mutation rate in a culture at 6 µg/mL was noted but this variation was not significant. However, this study was not deemed sufficient by the CSSC to determine the potential mutagenic effect of 4-MBC, among other reasons because it did not take into account chromosomal aberrations.

What are the risks posed by 4-MBC on reproduction and development?

Enzacamene is also associated with risks to reproduction and development. This is at least what some teratogenicity studies conducted on rats and rabbits suggest. In rats, exposure to doses of 30 and 100 mg/kg of body weight per day led to a delay in ossification in the foetuses, with a preferential location in the sternum in females and the extremities in males. These effects are associated with a decrease in the body weight of the mothers and foetuses, suggesting overall maternal toxicity.

Furthermore, a multigenerational reprotoxicity study in rats, in which only the parental generation (F0) females were exposed to 4-MBC, shows no notable effect on fertility or reproductive organs. However, a significant decrease in FSH is reported in the F1 generation males from a dose of 25 mg/kg of body weight per day. For reference, FSH is a hormone that stimulates the ovaries to produce eggs and the testes to produce sperm. The authors of the study attribute this variation to the hormonal dynamics related to puberty, rather than a direct impact on the hypothalamic-pituitary axis. Nevertheless, this interpretation should be taken with caution, as the study has several methodological limitations, such as the absence of treatment of F0 males, a small sample size, and a lack of precise quantitative data.

Is enzacamene an endocrine disruptor?

Available human data suggests that 4-MBC could potentially disrupt the hypothalamic-pituitary-thyroid axis, particularly after topical application. Several scientific studies support this concern. One such study was conducted on four volunteers who were acutely exposed to a relatively high dose of enzacamene (300 mg applied twice on a skin surface of 1,000 cm²). In women, this exposure led to a marked increase in TSH, a hormone that regulates the secretion of thyroid hormones T3 and T4 — up to 369% — as well as an increase in T3 and T4 levels. Conversely, in men, the effect was more moderate, with a slight increase in T3, while T4 and TSH remained largely stable. Although this study has several methodological uncertainties, the observed results seem consistent with those obtained in animals, reinforcing the hypothesis of an effect of 4-MBC on the functioning of the thyroid axis.

Currently, the SCCS believes there is not enough evidence to suggest that 4-MBC can act as an endocrine disruptor but recommends vigilance.