Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to para hydroxybenzoates (E 214-219)

No abstract available

The Scientific Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food has been asked to provide an opinion on the safety of paraben (E 214-219) usage in foods by 1 July 2004.

The EC Scientific Committee for Food (SCF) evaluated the parabens in 1994 and established a temporary Acceptable Daily Intake (ADI) of 0-10 mg/kg bw, as the sum of methyl, ethyl and propyl p-hydroxybenzoic acid esters and their sodium salts. The temporary ADI was based on long-term studies in rats with methyl, ethyl and propyl paraben. The ADI was made temporary because the SCF considered that the toxicological information available showed some inadequacies and uncertainties. The SCF therefore requested a new oral teratogenicity study in the rat using either free p-hydroxybenzoic acid or its methyl, ethyl or propyl ester and a cell proliferation study in the rat on the propyl ester of p-hydroxybenzoic acid given as a solution. In 2000, the SCF reiterated its wish to review the safety of parabens and at its last meeting in April 2003 the SCF noted that no data had been submitted by the food industry in support of the parabens and drew attention to its statement of October 2000, that the temporary ADI should be withdrawn if no further data were submitted.

The SCF had previously requested an oral teratogenicity study in the rat. The Panel evaluated newly available studies on the developmental toxicity of methyl paraben in rats, mice, hamsters, and rabbits which were not available to the SCF when it made its request for a teratogenicity study. No evidence of developmental toxicity up to and including the highest tested doses of 300 (rabbits) or 550 mg/kg body weight/day (rodents) were observed. The Panel concluded that no further data on developmental toxicity were needed.

The Panel also re-evaluated the proliferative effects of parabens on forestomach cells in rats, and concluded that the proliferative effect of parabens will only occur above a certain threshold and that the human exposure resulting from the use of parabens as preservatives in food will be much below such doses.

Consequently the Panel considered that the study previously requested by the SCF on cell proliferation in the rat on the propyl ester of p-hydroxybenzoic acid given as a solution were no longer needed.

Several parabens have shown oestrogenic activity in vitro. However, no oestrogenic activity could be detected in vivo for methyl, ethyl, and propyl parabens in classical uterotrophic assays using peroral or subcutaneous administrations of high doses to mice and rats. An in vivo uterotrophic effect was observed after subcutaneous injection of either butyl paraben or isobutyl paraben, which are not used as food additives. The common metabolite of parabens, p-hydroxybenzoic acid, was considered to be non-oestrogenic.

Dietary administration of propyl paraben to juvenile male rat for four weeks was reported to reduce the daily sperm production in the testis in all dose groups, including the lowest dose levels of 10 mg /kg body weight/day. At higher dose levels, reduced numbers of sperm cells, impaired spermatogenesis, and reduced testosterone levels were also observed. Thus, 10 mg/kg body weight/day was considered a Lowest Observed Adverse Effect Level (LOAEL) for propyl paraben. In contrast, methyl and ethyl paraben showed no effects on sex hormones and the male reproductive organs in juvenile rats at dose levels up to 1000 mg/kg body weight/day. Therefore 1000 mg/kg body weight/day was considered a No Observed Adverse Effect Level (NOAEL) for both methyl paraben and ethyl paraben.

The Panel established a full group ADI of 0-10 mg/kg bw for the sum of methyl and ethyl p-hydroxybenzoic acid esters and their sodium salts on the basis of the NOAELs of 1000 mg/kg bw/day for each compound in long-term toxicity studies and studies on sex hormones and the male reproductive organs in juvenile rats. The Panel considered that propyl paraben should not be included in this group ADI because propyl paraben, contrary to methyl and ethyl paraben, had effects on sex hormones and the male reproductive organs in juvenile rats.

The Panel is unable to recommend an ADI for propyl paraben because of the lack of a clear NOAEL.

para-Hydroxybenzoic acid alkyl esters, parabens, food additive, preservative