Scientific Opinion on the use of Basic Methacrylate Copolymer as a food additive

The Panel on Food Additives and Nutrient Sources added to Food provides a scientific opinion on the use of basic methacrylate copolymer (BMC) as a glazing agent in solid food supplements and in solid foods for special medical purposes. The NOAELs derived from the main studies are 1000 mg/kg bw/day (developmental study in rat, the only dose level tested) and 2000 mg/kg bw/day (26-week feeding study in rat, highest dose tested). BMC does not raise concern with respect to genotoxicity. No studies on reproductive toxicity were available and the database on developmental toxicity was limited. Therefore no ADI was derived. The estimated combined exposure for heavy users to BMC from both its use in food supplements and in pharmaceuticals is equal to 23.4 mg/kg bw/day for a 60 kg adult and 16 mg/kg bw/day for children (4-18 years). The calculated worst case exposure to the monomers (MMA, BMA, and DMAEMA) is < 50 µg/kg bw/day for adults and < 32 µg/kg bw/day for children, being significantly below the group TDI of 0.1 mg/kg bw/day (as methacrylic acid) set by the SCF. Using the above NOAELs, given a coating level of 100 mg/tablet and a combined exposure from food supplements and pharmaceuticals, the calculated margin of safety (MOS) for heavy users varies from at least 43 to 85 for adults and from 63 to 125 for children. The MOS from the exposure only from food supplements ranges from 85 to 171 for adults and from 125 to 250 for children. In the light of the high molecular weight of the substance, its lack of absorption and its low toxicity profile, the Panel considers these margins of safety adequate. In conclusion the use of BMC as a glazing agent/coating agent in solid food supplements is not of safety concern at the proposed use levels.

© European Food Safety Authority, 2010

Following a request from the European Commission to the European Food Safety Authority (EFSA), the Scientific Panel on Additives and Nutrient Sources added to Food (ANS) was asked to provide a scientific opinion on the use of basic methacrylate copolymer as a glazing agent in solid food supplements as defined by European Parliament and Council Directive 2002/46/EC, and in solid foods for special medical purposes as defined by Commission Directive 1999/21/EC.

The technological function of the substance is to provide moisture protection and to mask the taste of various nutrients present in the treated products.

The Panel considered the identity of the test substances used in the toxicological studies submitted by the petitioner as compared to the commercial substance. From the information provided by the petitioner it is deduced that the proportion of monomers in the copolymer are either identical or very similar to the substance used in the ADME study and in the six month oral toxicity study.

The petitioner provided studies on absorption, distribution, metabolim and excretion, acute and sub chronic oral toxicity, genotoxicity, and developmental toxicity of basic methacrylate copolymer.

Basic methacrylate copolymer is virtually not absorbed from the gastrointestinal tract after oral administration. This is in line with it being a stable high-molecular compound.

Based on negative results derived from a gene mutation assay in Salmonella typhimurium, an in vitro mammalian cell gene mutation assay in L5178Y mouse lymphoma cells and an in vivo micronucleus assay, each performed according to current OECD guidelines and in compliance with GLP, the Panel concludes that basic methacrylate copolymer does not raise concern with respect to genotoxicity.

In a 26-week rat study, no treatment-related effects were noted on body weight, body weight gain, and food or water consumption. No clinical signs were apparent to indicate a treatment-related effect. No macroscopic or microscopic abnormalities were noted that were deemed to be a result of treatment. A NOAEL of 2000 mg/kg bw/day, the highest dose tested, was identified.

In the 28-day dog study, the NOAEL was regarded as being 750 mg/kg bw/day, the highest dose tested. The Panel however, considers that this study is less relevant for risk assessment due to its duration.

From the developmental toxicity study no evidence was found of an effect of treatment on maternal animals. There were also no effects on fetal survival, and fetal weights and placental weights were unaffected by the treatment. A NOAEL for both dams and fetuses of 1000 mg/kg bw/day (the only dose level tested) can be derived.

No data were provided on chronic toxicity, however, given the high-molecular-weight of the substance and its lack of absorption, the Panel considers that such data are not required.

The Panel based its exposure estimate on the worst case combined exposure for heavy users (assuming a coating level of 100 mg/tablet) to basic methacrylate copolymer from both its proposed use in food supplements and from its approved use in pharmaceuticals to be equal to 23.4 mg/kg bw/day for a 60 kg adult and to 16 mg/kg bw/day for children (4-18 years), whereas the petitioner estimated this exposure to be 20 mg/kg bw/day and 16 mg/kg bw/day respectively.

The Panel estimated the combined exposure for heavy users to basic methacrylate copolymer with a normal maximum coating level of 30 mg/tablet, from both its proposed use in food supplements and from its approved use in pharmaceuticals to 7 mg/kg bw/day for a 60 kg adult and to 4.8 mg/kg bw/day for a child. The respective estimates by the petitioner for these user groups are 6 mg/kg bw/day and 4.8 mg/kg bw/day.

If basic methacrylate copolymer was only used in food supplements, at the normal coating level of 30 mg/tablet, the estimated exposure for heavy users would be 3.5 mg/kg bw/day for adult heavy users and 2.4 mg/kg bw/day for children.

Using the worst case exposure, the calculated exposure to the residual monomers (MMA, BMA, and DMAEMA) present in the substance would be less than 50 µg/kg bw/day for adults and less than 32 µg/kg bw/day for children. The Panel noted that these figures were significantly below the group TDI established by the SCF of 0.1 mg/kg bw/day for MMA and BMA expressed as methacrylic acid. For DMAEMA, the SCF noted that residues of this substance could not be detected (at LOD: 10 µg/kg), suggesting that DMAEMA is not labile from the polymer matrix. Therefore, this substance was not taken into account for calculating exposure.

The Panel noted that no data on reproductive toxicity were provided and that the database on developmental toxicity was limited. The Panel therefore considered that it could not derive an ADI for basic methacrylate copolymer.

The NOAELs derived from the available studies are: 1000 mg/kg bw/day from a developmental study in the rat (the only dose level tested) and 2000 mg/kg bw/day from a 26-week feeding study in the rat (highest dose tested).

Using this range of NOAELs and assuming a coating level of 100 mg/tablet and a combined exposure from food supplements and pharmaceuticals, the Panel calculates a margin of safety (MOS) for heavy users varying from at least 43 to 85 for adults and from 63 to 125 for children. If only the exposure from food supplements is considered the MOS ranges from 85 to 171 for adults and from 125 to 250 for children. In the light of the high molecular weight of the substance, its lack of absorption and its low toxicity profile, the Panel considers these margins of safety adequate.

The Panel notes that the petitioner did not provide use levels for basic methacrylate copolymer for uses in solid foods for special medical purposes (FSMPs). Therefore, the safety of this usage could not be evaluated.

The Panel concludes that the use of basic methacrylate copolymer used as a glazing agent/coating agent in solid food supplements is not of safety concern at the proposed use levels.

basic methacrylate copolymer; Poly(butyl methacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate) 1:2:1. CAS 24938-16-7; Amino methacrylate copolymer; Aminoalkyl methacrylate copolymer E