欧盟拟批准间苯二酚作为食品添加剂

    我们导读：2010年1月18日，欧盟食品安全局报道，欧盟拟批准间苯二酚作为食品添加剂，在甲壳类产品中用作抗氧化剂，用以抑制其酶促褐变问题。

    原文报道：

Following a request from the European Commission to the European Food Safety Authority (EFSA), the Scientific Panel on Food Additives and Nutrient Sources added to Food (ANS) was asked to provide a scientific opinion on the safety of resorcinol when used as an antioxidant in crustaceans.

Resorcinol is a specific inhibitor of polyphenol oxidase and therefore it can act as an anti-browning agent in fresh, frozen and deep-frozen crustaceans. Specifications for resorcinol indicated by the petitioner are: the minimum purity of resorcinol is 99 % (stated range of 99.0-100.5 % by iodometry assay), insoluble matter is set at 0.005 % and the residue after ignition 0.01 % maximum. The anti-browning agent intended to be authorised contains resorcinol as a main ingredient (more than 99.5 %) and citric or ascorbic acid at less than 0.3 %.

The petitioner proposes to use resorcinol at a concentration of 5 to 7 g/L in the dipping solution for a dipping time of 4-5 minutes. Under these treatment conditions, the residual resorcinol measured in raw shrimps (whole product) was 120 mg/kg, in edible parts of raw shrimps was 30 mg/kg, and in edible parts of boiled shrimps was 15 mg/kg bw.

Resorcinol is rapidly absorbed from the gastrointestinal tract, metabolised extensively to sulphate and/or glucuronic acid conjugates and excreted primarily in the urine. Studies with 14C-radiolabelled resorcinol administered by gavage indicated no accumulation.

Resorcinol is of moderate acute toxicity. The reported LD50 values in rats ranged from 200 mg/kg bw to 980 mg/kg bw depending on the study.

The subchronic toxicity studies in rats and mice indicate a steep dose-response curve for lethality, with lethal effects observed at 520 mg/kg bw/day in rats and at 420 mg/kg bw/day or above in mice. At doses that are not lethal, clinical signs of toxicity manifested by hyperexcitability, tachypnoea, ataxia, prostration, and tremors were observed in mice and rats in subacute, subchronic and chronic toxicity studies.

Other effects reported in subchronic studies at doses that were not lethal were, increased absolute and relative liver weights in rats of both sexes, and increased absolute and relative adrenal weights in male rats, and decreased absolute and relative adrenal weights in male mice. The Panel noted that these changes in organ weights were slight, with no marked dose-response relationship, and were not accompanied by any changes in clinical chemistry parameters indicative of impairment of the liver function, or by any histopathological changes in the liver or adrenals and therefore the Panel did not consider these findings to be biologically significant,
Carcinogenicity studies in rats and mice demonstrated the lack of carcinogenic activity of resorcinol. However, clinical signs of toxicity in treated rats (ataxia, prostration, salivation and tremors) and mice (recumbency and tremors) of both sexes were seen at about 100 mg resorcinol/kg bw/day (5 days per week) and above. These acute signs occurred shortly after dosing and disappeared after approximately 30 to 60 minutes. The no-observed-adverse-effect-level (NOAEL) for these acute neurological effects was 50 mg/kg bw/day, which corresponds to 36 mg/kg bw/day when adjusted from the 5-day dosing week to a 7-day dosing week. The Panel considered these acute neurological effects as critical endpoints in the evaluation of resorcinol toxicity.

Resorcinol was tested in genotoxicity tests covering the three types of genotoxic endpoints, i.e. gene mutations in bacteria and gene mutations and chromosomal aberrations in mammalian cell in vitro. Four in vitro and one in vivo study were conducted according to GLP and in compliance with the relevant OECD test guidelines and additional  non-GLP genotoxicity studies were also available. Overall, resorcinol did not induce mutations in bacteria in tests which were performed according to current guidelines; however, resorcinol induced reverse mutations in one study in Salmonella typhimurium strain TA100 without metabolic activation and in strain TA1535 with metabolic activation when tested with a certain bacterial minimal medium. Resorcinol was clastogenic in vitro in peripheral human lymphocytes in the absence of metabolic activation. The results from an in vitro mouse lymphoma assay indicated that resorcinol could induce gene mutations and/or chromosomal aberrations; however, resorcinol did not induce mutation at the hprt locus of L5178Y mouse lymphoma cells when tested in concentrations up to 1101 µg/mL (10 mM) in two independent experiments in the absence or presence of a rat liver metabolic activation system (S9). A valid in vivo mouse micronucleus assay was negative. Thus, the clastogenic effects observed in some in vitro assays were not confirmed in vivo. Therefore, the Panel considered that there was no concern with respect to genotoxicity.

Resorcinol had no adverse effects on the developing fetus when administered to pregnant rats by gavage in doses up to 500 mg/kg bw/day from gestation days 6 to 15, or as a single dose of 1000 mg/kg bw on gestation day 11, or in rabbits in doses up to 100 mg/kg bw/day given by gavage from gestation days 6 to 18. No maternal toxicity was recorded at these dose levels.

Intake of resorcinol in drinking water in a one-generation dose-range finding reproductive toxicity study in rats and in a two-generation reproductive toxicity study in rats in doses amounting up to 233 and 304 mg/kg bw/day for males and females respectively was not associated with reproductive toxicity. In these studies no adverse effects were seen on function and morphology of the thyroid.

The Panel considers the acute clinical signs of toxicity to be the pivotal adverse effect of resorcinol and subsequently derived an ADI from the NOAEL of 50 mg/kg bw/day for these effects in the carcinogenicity study in rats (which corresponds to 36 mg resorcinol/kg bw/day when adjusting the 5-day dosing week to a 7-day dosing week). Because of the steep dose-response curve for resorcinol-induced lethality in acute and chronic animal experiments and the observed species and strain differences the Panel found it appropriate to apply an additional safety factor of 3 to a safety factor of 100 and established an ADI of 0.12 mg/kg bw/day for resorcinol.

The Panel assessed the acute and chronic exposure to resorcinol based on two scenarios resulting in different resorcinol concentrations.

The first scenario corresponds to the use proposed by the petitioner: resorcinol concentration of 5-7 g/L in the dipping solution with a dipping time of 4-5 minutes. The reported residual resorcinol concentrations using these treatment conditions were 120 mg/kg in raw shrimps (whole product), 30 mg/kg in the edible parts of raw shrimps, and 15 mg/kg in the edible parts of boiled shrimps.

In the second scenario, a dipping time of 30 minutes in a solution containing 5-7 g/L resorcinol was considered. The reported residual resorcinol concentrations using these treatment conditions were 470 mg/kg in raw shrimps (whole product), 40 mg/kg in the edible parts of raw shrimps, and 78 mg/kg in the edible parts of boiled shrimps.

For the acute exposure to resorcinol for adults and children, the Panel estimated consumption per eating occasion of 250 g of peeled cooked shrimps or 100 g of whole cooked shrimps as an ingredient of mixed dishes. In the absence of data on resorcinol concentration in cooked dishes prepared with raw shrimps (e.g. paella), it was assumed that the amount of resorcinol originally present in the whole raw shrimps would be present in the whole dish. For the chronic exposure to resorcinol, an estimated level of daily consumption of 50 g of shrimps on a regular basis was considered by the Panel to be sufficiently conservative to cover the food habits of the European population including high consumers. The acute daily exposure ranged from 0.06 to 0.8 mg/kg bw for adults and from 0.12 to 1.6 mg/kg bw for children, depending on the residual concentration of resorcinol. The chronic daily exposure ranged from 0.1 to 0.4 mg/kg bw for adults and from 0.2 to 0.8 mg/kg bw for children consumption, again depending on the residual concentration of resorcinol.

The highest calculated daily exposure to resorcinol corresponds to the consumption of cooked dishes prepared with 100 g of whole raw shrimps as an ingredient. The corresponding figures amount to 0.2-0.8 mg resorcinol/kg bw for adults and 0.4-1.6 for children. The Panel noted that the exposure would always exceed the ADI for adults and children with the residual resorcinol concentrations considered for whole raw shrimps (120 mg/kg or 470 mg/kg according to dipping time).

In view of exceeding the ADI in these scenarios, the Panel calculated the maximum residual concentration of resorcinol in whole raw shrimps that would not lead to an exposure exceeding the ADI of 0.12 mg/kg bw in the most vulnerable population (children) in any of the exposure scenarios considered. This residual concentration of resorcinol amounts to 35 mg/kg. This defined value is only applicable if other usages of resorcinol are excluded.

The Panel noted that the proposed uses are for all crustaceans but that only experimental data on shrimps have been reported. The current evaluation is therefore related only to the use of resorcinol on raw shrimps and dietary exposure should be re-estimated if new usages are introduced.

    详情见：http://www.efsa.europa.eu/en/scdocs/scdoc/1411.htm?WT.mc_id=EFSAHL01&emt=1