Scientific Opinion on the re‐evaluation of 4‐hexylresorcinol (E 586) as a food additive

Abstract

The Panel on Additives and Nutrient Sources added to Food (ANS) delivers an opinion re-evaluating the safety of an antioxidant 4-hexylresorcinol (4-HR) (E 586). The SCF in 2003 and the JECFA in 1996 recognised that available database was not sufficient to establish an ADI but considered 4-HR toxicologically acceptable for prevention of melanosis in shrimps provided residues in crustacean meat did not exceed 2 mg/kg (SCF) or 1 mg/kg (JECFA). The Panel was not provided with a newly submitted dossier and no new toxicological or biological information was submitted for the present re-evaluation following a public call for data and based its evaluation on previous evaluations and additional literature that became available since then. The Panel agreed with the SCF that the database did not allow the establishment of an ADI. The Panel considered nephropathy in mice as the most sensitive endpoint for 4-HR toxicity. The lowest BMDL10 for nephropathy in carcinogenicity study in mice (4 mg/kg bw/day) and the highest exposure estimate (3.3 µg/kg bw/day, adults, 95th percentile of consumers only) provided the MoS considered by the Panel as sufficient given the conservative nature of exposure estimates and limited uses. The Panel concluded that 4-HR was toxicologically acceptable for prevention of melanosis in shrimps and related crustaceans provided that residues in crustacean meat do not exceed 2 mg/kg. The Panel concluded that any increase in the permitted use would require additional reproductive toxicity studies. As the information on actual residual levels in crustaceans was limited the Panel recommended monitoring of these levels in the European market.

Comprehensive interpretation of in vitro micronucleus test results for 292 chemicals: from hazard identification to risk assessment application

“…In contrast, there is evidence that 5-pentylresorcinol, another structural analog of 4-hexylresorcinol, may disrupt microtubule and spindle formation through a decrease in DNA synthesis and indirect induction of abnormal anaphase configurations (National Toxicology Program 1988 ), indicating that it is a potential aneugen. In the EFSA re-evaluation of 4-hexylresorcinol as a food additive, the panel concluded that there was no safety concern of genotoxicity or carcinogenicity for 4-hexylresorcinol based on its current use levels (European Food Safety Authority 2014 ). However, the panel noted that there were no reproductive and developmental toxicity studies, and that a one-generation study would be required before permitting an increase in usage level.…”