Maximum residue limits , food

The previous chapters examined the process for the development and authorisation of a drug product containing a ne v active ingredient for human use. This represents the most arduous path to market for any medicinal product. This chapter proceeds to examine the process of bringing a veterinary medicinal product to market. While the process shares most of the principles that apply to human drugs, there are some additional features that are unique to veterinary products. These include methods of use and the requirement to evaluate vithdra val periods and maximum residue limits in food-producing species. 

A unique feature of the development of veterinary medicines for food-producing species is the need to consider the establishment of Maximum Residue Limits (M RLs) for the drug or its metabolites in food produce. A MRL is defined in the European Union as ... 

TheFood Sanitary Law in Japan, which is regulated by theMinistry of Health, Labor and Welfare (MHLW), has established maximum residue limits (MRLs) and monitors the residue levels in food commodities in the market, including both domestic and... 

Today, when a pesticide with no detectable residues is registered for use, a Tolerance or maximum residue limit (MRL) is established at the lowest concentration level at which the method was validated. However, for risk assessment purposes it would be wrong to use this number in calculating the risk posed to humans by exposure to the pesticide from the consumption of the food product. This would be assuming that the amount of the pesticide present in all food products treated with the pesticide and for which no detectable residues were found is just less than the lowest level of method validation (LLMV). The assumption is wrong, but there is no better way of performing a risk assessment calculation unless the limit of detection (LOD) and limit of quantification (LOQ) of the method were clearly defined in a uniformly acceptable manner. 

Codex Guideline EMRL(1)-1997, List of Codex Extraneous Maximum Residue Limits in Food , Codex Alimentarius Commission, Washington, DC (1997). 

Pesticide residues consist of chemicals that might occur in a commodity as a result of application of a pesticide. Such chemicals typically correspond to compounds for which a regulatory agency has or will set a tolerance, i.e., a maximum residue limit, specific to the commodity. In either a field study or a market basket survey, residues to be determined will be those which result from application of the specific pesticide that the study is intended to support. A market basket survey, however, might be intended to support not just one but several different pesticides of the same or different chemical classes. In addition, a market basket survey might include pesticides not used in the USA but for which import tolerances exist. For example, some uses of the parathion family of pesticides on food products have been abandoned in the USA but remain in other countries that export the products to the USA. A market basket survey offers a means to evaluate actual dietary exposures to residues of such pesticides. In addition, tolerance expressions frequently include multiple compounds, all of which must typically be determined in residue field trials. The sponsor of the market basket survey must decide whether to analyze for all compounds in the applicable tolerance expression or to restrict the program to selected analytes, such as the active ingredient. 

Sulfonylurea herbicides are generally applied to crops as an early post-emergent herbicide. Crops that are tolerant to these herbicides quickly metabolize them to innocuous compounds. At maturity, residues of the parent compound in food and feed commodities are nondetectable. Metabolites are not considered to be of concern, and their levels are usually nondetectable also. For this reason, the residue definition only includes the parent compound. Tolerances [or maximum residue limits (MRLs)] are based on the LOQ of the method submitted for enforcement purposes and usually range from 0.01 to 0.05 mg kg (ppm) for food items and up to O.lmgkg" for feed items. There is no practical need for residue methods for animal tissues or animal-derived products such as milk, meat, and eggs. Sulfonylurea herbicides are not found in animal feed items, as mentioned above. Furthermore, sulfonylurea herbicides intentionally dosed to rats and goats are mostly excreted in the urine and feces, and the traces that are absorbed are rapidly metabolized to nontoxic compounds. For this reason, no descriptions of methods for animal-derived matrices are given here. 

In Japan, bifenox is the only registered diphenyl ether herbicide. The tolerance and/or maximum residue limits (MRLs) are established at 0.1 mg kg for cereals such as rice grain, barley and wheat, and 0.05mgkg for potatoes (Ministry of Health, Labour and Welfare, Japan). Ibe California Department of Food and Agriculture (CDFA) established the minimum detectable quantity of diphenyl ether herbicides at 0.1 mgkg for bifenox, nitrofen and oxyfluorfen. ... 

Oxime carbamates are generally applied either directly to the tilled soil or sprayed on crops. One of the advantages of oxime carbamates is their short persistence on plants. They are readily degraded into their metabolites shortly after application. However, some of these metabolites have insecticidal properties even more potent than those of the parent compound. For example, the oxidative product of aldicarb is aldicarb sulfoxide, which is observed to be 10-20 times more active as a cholinesterase inhibitor than aldicarb. Other oxime carbamates (e.g., methomyl) have degradates which show no insecticidal activity, have low to negligible ecotoxicity and mammalian toxicity relative to the parent, and are normally nondetectable in crops. Therefore, the residue definition may include the parent oxime carbamate (e.g., methomyl) or parent and metabolites (e.g., aldicarb and its sulfoxide and sulfone metabolites). The tolerance or maximum residue limit (MRL) of pesticides on any food commodity is based on the highest residue concentration detected on mature crops at harvest or the LOQ of the method submitted for enforcement purposes if no detectable residues are found. For example, the tolerances of methomyl in US food commodities range from 0.1 to 6 mg kg for food items and up to 40 mg kg for feed items. ... 

Oxytetracycline is a broad-spectrum antibiotic, which has been used worldwide in veterinary medicine and in aquaculture for the prevention and treatment of disease and as feed additives to promote growth. The maximum residue limits (MRLs) of OTC and relative substances as described by the US Food and Drug Administration [66] and European Union [67] are presented in Table 4. 

While all nations of the world possess the sovereign right to establish their own acceptable levels for pesticide residues in foods, many lack the resources to develop their own regulatory programs and instead rely upon a set of international standards developed by the Codex Alimentarius Commission, frequently referred to as Codex. The Codex international standards are termed maximum residue limits (MRLs) and, like U.S. tolerances, are established primarily as enforcement tools for determining whether pesticide applications are made according to established directions. While many countries have adopted Codex MRLs, others, such as the U.S. and several Asian countries, rely on their own standards. Thus, there is no uniformity among the world with respect to allowable levels of pesticides on foods. A pesticide-commodity... 

Examples of standard settings developed by the WHO include air quality guidelines (Section 9.2.1.1) and drinking water guidelines (Section 9.2.1.2), and (in collaboration with the FAO) maximum residue limits (MRLs) for pesticides and veterinary drugs and maximum levels for food additives (Section 9.2.1.3). 

After an ADI has been determined, it is essential that a maximum residue limit (MRL) in each particular edible animal product be specified so that its consumption by humans will not result in a residue intake exceeding the ADI. The elaboration of MRLs depends on a number of food intake factors including the likely degree of consumption of the edible animal product in question and the normal dietary habits among the population. Currently, there is much debate over these factors and their realistic evaluation for the commodities involved. 

Under the pressure of an increasing number of drugs with fixed tolerance or maximum residue limits (MRLs), demands on methods to detect antimicrobial residues in edible animal products have changed markedly during recent decades (1). To satisfy these demands and prevent contaminated products from entering the food chain, many microbiological tests with sufficient detection sensitivity of as many analytes as possible in animal tissues, milk, eggs, honey, and fish have been developed or modified. 

To safeguard human health, the European Union (EU) has established safe maximum residue limits (MRLs) for residues of veterinary drugs in animal and food samples (2,3). The Council Directive 96/23/EU has established numbers of samples to be tested for each compound group (4). 

To undertake a risk assessment on the consumption of food, the first step is to compare the levels with the maximum residue limits (MRLs). MRLs for POPs in Singapore (Government of Singapore, 1990) and the United States (USFDA, 2001) are presented in Table 16.6. Samples were lower than respective MRLs for all POPs. 

Since its inception, the CA Commission has produced a large volume of standards, codes of practice, and guidelines. It has developed more than 220 commodity standards, more than 40 codes of practice, a model food law, a code of ethics, and limits for more than 500 food additives. In addition, the commission scrutinized 2,000 pesticides and established limits on 200 of them (Mendez 1993). The work on pesticide residues has resulted in establishing maximum residue limits (MRLs) for a wide range of pesticides in many food commodities. The... 

When calculating chronic dietary exposure, the deterministic models use point values for both food consumption and residue concentration, thereby yielding a point estimate of dietary exposure. In the US, the initial chronic dietary exposure estimate is the Theoretical Maximum Residue Contribution (TMRC) and is analogous to the Theoretical Maximum Daily Intake (TMDI) used to estimate chronic dietary exposure in the EU. Both the TMRC and the TMDI are relatively conservative estimates of dietary expostire. The TMRC is calculated as the product of the mean consumption value and the US pesticide tolerance [6]. In the EU, the TMDI is calculated as the product of the mean consumption value and the Maximum Residue Limit (MRL) [7]. The objective of both calculations is essentially identical to calculate an estimate of the central tendency of the dietary exposure. Both calculated values use the central tendency dietary exposure estimate as the estimate of chronic (long-term) dietary exposure and calculate it using mean consumption data and the maximum residue permitted on the commodity. 

Specialists invited to serve as members of JECFA are independent scientists who serve in their individual capacities as experts and not as representatives of their governments or employers. They also understand that the discussions at the meetings are confidential. The goal is to establish acceptable daily intakes (ADIs) (or equivalent tolerable intakes) for food chemicals and to develop specifications for identity and purity for food additives or maximum residue limits (MRLs) when veterinary drugs are used in accordance with good practice in the use of veterinary drugs. 

Name Conditions of use (summary description of extraction) Maximum residue limits in the extracted foodstuff of food ingredient... 

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