Pesticides, acceptable daily intake

Several aspects of the problem of herbicides being contaminated with nitrosamines, and the resulting inadvertent introduction of nitrosamines into the environment, will be discussed in other papers in this symposium. Unrecognized until less than five years ago, the situation has inspired intense debate and prompted several of the environmental chemistry studies mentioned in this paper. Like the presumed threat from the in vivo nitros-ation of pesticide residues, discussions sometimes lack the type of anticipated dose and effect calculations just mentioned. Unlike the active ingredients, whose benefits can justify residue tolerances and acceptable daily intakes, nitrosamine contaminents afford no known benefits, and the desirability of minimizing their levels is undisputed. 

In September 1999, the United Nations World Health Organization (WHO) and the Food and Agriculture Organization (FAO) Joint Meeting on Pesticide Residues (JMPR) established an acute reference dose (RfD) of 0.1 mg/kg bw and a chronic RfD, or acceptable daily intake (ADI), of 0.01 mg/kg bw/day. (See FAO/WHO Report 153, Pesticide Residues in Pood, Section 4.7, Chlorpyrifos, 1999.)... 

An added ten-fold safety factor shall be added in setting pesticide reference doses (RfDs) (i.e. acceptable daily intakes) to account for the unique risks faced by infants and children, unless the EPA administrator has solid data supporting a determination that existing RfDs are fully health protective, even for infants and that exposures are fully and accurately characterized and... 

Pesticide residues were analyzed in 183 milk samples from 165 Finnish women. Heptachlor was found in 12% of the samples heptachlor epoxide was found in 6.6%. Five percent of the samples contained levels of heptachlor epoxide in excess of 0.0005 mg/kg body weight, an acceptable daily intake (Mussalo-Rauhamaa et al. 1988). Fifteen milk and fat specimens from residents of Grand Forks, British Columbia, and 16 milk and 17 fat specimens from residents of Prince George, British Columbia, were analyzed for pesticide residues. Heptachlor epoxide was found in one milk sample and nine fat samples in the Grand Forks group (>0.004 ppm) and in no milk samples and two fat samples in the Prince George group (>0.004 ppm) (Larsen et al. 1971). The residue was not detectable at levels lower than 0.004 ppm because of limitations of the analytical methods and faulty techniques. It is possible that the potential exposure of the residents to heptachlor may also have occurred via food contaminated with heptachlor. 

In 1961, the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and the Joint Meeting of Experts on Pesticides Residues (JMPR) adopted this approach in a slightly modified form The safe level was called the Acceptable Daily Intake (ADI) and expressed in mg/kg body weight per day (Vermeire et al. 1999, ECETOC 2003). Usually, a safety factor of 100 is used by JECFA and JMPR for establishing ADIs by this ADI approach however, the procedures adopted by JECFA and JMPR do not generate a clear justification for deviation from the factor of 100, but in some individual cases, an expert explanation is given for the use of factors other than 100 (Vermeire et al. 1999). 

Ito, N., R. Hasegawa. K. Imaida, Y. Kurata, A. Hagiwara, and T. Shirai. 1995. Effect of ingestion of 20 pesticides in combination at acceptable daily intake levels on rat liver carcinogenesis. Food Chem. Toxicol. 33 159-163. 

ADI Acceptable daily intake - "The daily intake of chemical, which during an entire lifetime appears to be without appreciable risk on the basis of all known facts at that time" Food additives, pesticides... 

When considering the establishment of the initial tolerance for a specific pesticide on a food item—and also when considering the establishment of each succeeding tolerance for that pesticide on subsequent food items—the Agency compares the TMRC with the Acceptable Daily Intake, the ADI, to determine whether granting the proposed tolerance(s) would result in an unsafe of residue in food. 

The estimation of the Actual Daily Exposure assuming a person consumes a large portion of food. If this one-day exposure exceeds the Acceptable Daily Intake, then this use of the pesticide could be denied. 

Toxic chemical intake must be quantified in order that comparisons between different chemicals (e.g. pesticides), diets and countries can be made. Most countries in the developed world conduct surveys which involve analysing food for pesticide residues. These values are then put in context by comparing them to benchmarks of toxicity (Acceptable Daily Intake - ADI) or with trading standards (Maximum Residue Level -MRL) which are set to ensure that countries exporting food do not export excessive pesticide residues with that food. 

When proposing an MRL, the Rapporteur Member State (RMS) identifies the Acceptable Daily Intake (ADI) and Acute Reference Dose (ARfD) for man that is valid for the pesticide in question. The ADI thus identified is often the same as that recommended by the Joint FAO/WHO Meetings on Pesticide Residues (JMPR), whose recommendations on ADIs and MRLs are used within the Codex Alimentarius system. If the ADI proposed by the RMS is not that recommended by JMPR, the RMS has to provide an explanation for the difference. The other Member States comment on the RMS proposal at meetings of the Working Group on Pesticide Residues. If the Member States cannot reach agreement on the evaluation, the matter is referred to one or more of the Commission s scientific advisory committees. Prior to autumn 1997, such questions were referred to the Scientific Committee for Pesticides, but since then they have been referred to the Scientific Committee on Plants. 

This maximum legal exposure, often referred to as the Theoretical Maximum Residue Contribution, or TMRC, is compared with established toxicological criteria such as the reference dose (RfD) or Acceptable Daily Intake (ADI) which represent, after analysis of animal toxicology data and extrapolations to humans, the daily exposure that is not considered to present any appreciable level of risk. When it is determined that the TMRC exposure is below the RfD or ADI, the EPA usually considers the risks from the pesticide in question to be negligible and approves the manufacturer s petition to establish a tolerance at or slightly greater than the maximum levels identified from the manufacturer s controlled field trials (Winter, 1992a). 

Table 17.5. Acceptable daily intakes for organochlorine pesticides...

ADI Acceptable Daily Intake the amount of a specific food additive or contaminant (e.g., pesticide) thought to be the maximum level that should be consumed on a daily basis. ADI values are normally determined by experts of WHO and FAO Codex Alimentarius Committee. 

The tolerance on each food is set sufficiently low that daily consumption of the particular food or of all foods treated with the particular pesticide will not result in an exposure that exceeds the acceptable daily intake (ADI) for the pesticide. The tolerance is set still lower if the effective use of the pesticide results in lower residues. 

Lu FC (1995) A review of the acceptable daily intakes of pesticides assessed by the World Health Organization. Regulatory Toxicology and Pharmacology 21 351-364. 

The accepted daily intake for azamethiphos is 0.025 mg kg day As this pesticide is not used... 

Maximum residue limits have been recommended by the Joint FAO/WHO Meeting on Pesticide Residues. An acceptable daily intake of 0-0.02 mg kg body weight was established for fenvalerate by JMPR in 1986. 

The prototypical safety assessment for food-borne compounds is the acceptable daily intake (ADI) methodology, which was first documented in 1954, and has come to be employed throughout the world. This paradigm has also been codified in the consideration of food (e.g., aspartame) and color additives (e.g.. Red Dye No. 2), and pesticides (e.g., atrazine). It is also routinely used in the consideration of incidental food-borne chemical contaminants (e.g., lead), particularly as a tool for screening out trivial incidents of exposure. This procedure specifies that an acceptable dose of a chemical may be calculated with the following equation ... 

See also Acceptable Daily Intake (ADI) Food Additives Food and Agriculture Organization of the United Nations Food and Drug Administration, US Pesticides. 

The acceptable daily intakes set by the Joint Meeting on Pesticide Residues (JMPR) for cypermethrin, deltamethrin, and permethrin are 0-0.01 mg kg body weight, with acute oral reference doses for deltamethrin or permethrin of 0.05 mg kg bw. The National Institute for Occupational Safety and Health maximum allowable concentration (MAC) for pyrethrins at an 8 h time-weighted average is 5 mg m ... 

Field residues, if below the toxicological limit (acceptable daily intake), are used to set the legal limit. The residues of pesticides in the field experiment are affected by the environmental conditions such as temperature, wind, rain, solar irradiance etc. For this reason, residues limits (MRLs) can vary between countries because of the different climatic conditions, leading to EU trade difficulties. 

For pesticides not included in the Pharmacopoeial list, a formula based on the Acceptable Daily Intake (ADI) for the particular chemicals, as published by the Food and Agriculture Organisation (FAO-WHO), is used to determine the permitted level. The Pharmacopoeia recognises that many pesticides are poorly soluble and that an extraction method used to produce extracts, tinctures etc. can modify the content of pesticides in the finished product. In such cases the calculation of the limit includes an extraction factor. 

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