Maximum residue limit MRL

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. 

Development and Validation of a Proposed Regulatory Method, EMEA/CVMP/573100, Vol. 8, Veterinary Medicinal Products Establishment of Maximum Residue Limits (MRLs) for Residues of Veterinary Products in Foodstuffs of Animal Origin, Committee for Veterinary Medicinal Products, London (2001). Also available on the World Wide Web http //www.emea.eu.int/pdfs/vet/swp/057300en.pdf. 

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. ... 

Quantitative immunoassays have also been used as screening devices to determine whether drug residues exceed established maximum residue limits (MRLs) or tolerances in edible tissues. " For these applications, a cut-off value is set at the tolerance or MRL samples detected above this level are positive , and samples below this level are negative. ... 

Table 3 Examples of therapeutic agent maximum residue limits (MRLs) (mg kg ) from EU and tolerance levels (TLs) (mgkg- )fromUSEDA ...

The European Community guidelines specify that the maximum residue limit (MRL) for alkylenebis(dithiocarbamates) in fruits and vegetables is 0.05 mg carbon disulfide (CS2)kg ... 

Confirmation of the identity of an analyte should be performed particularly in those cases in which it would appear that a maximum residue limit (MRL) has been exceeded or in which a compound seems to be present which is not to expected in the sample being analyzed. 

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... 

When the EMEA began operations in January 1995, maximum residue limits (MRLs) had to be established for more than 600 substances. The assessment of these products has been completed before the January 2000 deadline. 

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). 

Milk from lactating cows intramuscularly injected with radiolabeled ceftiofur was found to contain 103 and 50 ppb of total residues at 12 and 24 h, respectively, postdosing. No parent ceftiofur could be detected in milk (85). Therefore, use of ceftiofur at the approved dosage and route is not expected to result in ceftiofiir-related residues exceeding maximum residue limit (MRL) at any time postdosing, and no milk withdrawal periods need to be assigned for ceftiofur. In addition, ceftiofur residues are not hazardous to industrial cheese and yogurt starter cultures. 

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. 

Table 11.1 Maximum Residue Limits (MRLs) and Acceptable Daily Intake (ADI) for Veterinary Medicinal Products in Foodstuffs of Animal Origin According to the Codex Alimentarius... 

Some critical differences in risk assessment procedure lead to confusing situations on a worldwide basis. These differences are due to some very controversial areas of safety issues including the calculation of the acceptable daily intake (ADI), the assignment of the ADI to maximum residue limit (MRL)/tolerance, the validation of the analytical methods needed to regulate drug residues, and the fitness of legislation to toxicology. 

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). 

European Union regulation foresees a maximum residue limit (MRL) for dichlorvos in durum wheat at 2.0 pg/g [4], Dichlorvos is also classified as a probable human carcinogen on the basis of the effects observed in mice and rats. Therefore, the U.S. Environmental Protection Agency (EPA) proposed cancellation of most uses of dichlorvos and proposed... 

The withdrawal period is set at the time taken for residues to fall to a concentration below the maximum residue limit (MRL) in each tissue - where an MRL has been set for a particular tissue and animal species, and allows a reasonable margin of error to allow for individual variations. For drugs where no safe concentration can be defined, for example in the case of some carcinogens, the limit of determination of the most sensitive analytical method available is usually used. 

In 1987 the CCRVDF Committee began the process of developing maximum residue limits (MRLs) and has agreed and adopted the following definition of an MRL ... 

Rules governing medicinal products in the European Community. Volume VI. Establishment by the European Community of maximum residue limits (MRLs) for residues of veterinary medicinal products in foodstuffs of animal origin. Commission of the European Communities. Directorate-General for Internal Market and Industrial Affairs. October 1991. 

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