Food additives quantitative risk assessment

In certain cases, the FDA has applied a negligible risk concept for food additives. This is demonstrated in the case of dimethyl dicarbamate, a yeast inhibitor for use in beverages (FDA 2000). The additive evenmaUy decomposes to methanol and carbon dioxide, but in the presence of ammonium ions (not uncommon in certain beverages) a carcinogenic chemical may also be formed in small amounts. The FDA used formal quantitative risk assessment procedures to estimate the upper-bound limit of carcinogenic risk to humans posed by urethane generated by decomposition of the additive. It was concluded that the potential risk was sufficiently low that the additive would be safe for the requested use, and the FDA s final rule approved its use (56 FR 40502 1988). 

EPA released the first case study of cumulative risks from 24 OPs in food for scientific review in mid-2000. Public comments were solicited and several scientific panel (SAP) meetings were held on various aspects of EPA s quantitative methods. In December 2001 a preliminary OP-CRA (cumulative risk assessment) was released, this time encompassing 30 OPs, additional foods, more residue data and all major routes of exposure. Public comments were solicited again and another series of SAP meetings were held. The revised final OP-CRA was issued in June 2002 after more than 20 SAP meetings and four rounds of public comment (US Environmental Protection Agency, 2002). It is the most sophisticated and data-rich pesticide risk assessment ever carried out. 

The 1996 Food Quality Protection Act (FQPA) now requires that an additional safety factor of 10 be used in the risk assessment of pesticides to ensure the safety of infants and children, unless the EPA can show that an adequate margin of safety is assured with out it (Scheuplein, 2000). The rational behind this additional safety factor is that infants and children have different dietary consumption patterns than adults and infants, and children are more susceptible to toxicants than adults. We do know from pharmacokinetics studies with various human pharmaceuticals that drug elimination is slower in infants up to 6 months of age than in adults, and therefore the potential exists for greater tissue concentrations and vulnerability for neonatal and postnatal effects. Based on these observations, the US EPA supports a default safety factor greater or less than 10, which may be used on the basis of reliable data. However, there are few scientific data from humans or animals that permit comparisons of sensitivities of children and adults, but there are some examples, such as lead, where children are the more sensitive population. It some cases qualitative differences in age-related susceptibility are small beyond 6 months of age, and quantitative differences in toxicity between children and adults can sometimes be less than a factor of 2 or 3. 

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