Regulating Pesticides in Food The Delaney Paradox (1987) / Chapter Skim
Currently Skimming:
Appendix C: Case Studies of the EPA's Application of the Delaney Clause in the Tolerance-Setting Process
Appendix C: Case Studies of the EPA's Application of the Delaney Clause in the Tolerance-Setting Process
Pages 196-225
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 196... ...
Descriptions of each chemical are included along with regulatory status, special review criteria that have been triggered, oncogenic findings and risk estimation, alternative pesticides, and a discussion of issues relevant to tolerances and the Delaney Clause (section 409~. FOSETYL AL Description of the Chemical Common name: Aluminum tris (ethyl phosphonate)
|
From page 197... ...
The only oncogenic effect observed was that mentioned above. The oncogenic risk from dietary exposure to fosetyl A1 is calculated by the EPA at about 1 x 10-8, or 1 in 100 million.
|
From page 198... ...
New sections 408 and 409 feed additive tolerances were issued for Benomyl in wheat, barley, and other small grains on November 7, 1984. Regulatory Status A notice of Rebuttable Presumption Against Registration (RPAR, now known as a special review)
|
From page 199... ...
Special Review Criteria Triggered Reduction in nontarget species Mutagenicity Teratogenicity Reproductive effects Hazard to wildlife Summary of Oncogenic Findings and Risk Estimation In tests with benomyl, hepatocellular carcinomas or combined hepatocellular neoplasms in both male and female mice were observed at all doses (the low dose was 500 ppm)
|
From page 200... ...
These uses account for around 1.1 million pounds of benomyl applications, or approximately one-third of all benomyl sales. Reduction in estimated dietary oncogenic risk from revocation of these tolerances would largely be a function of the oncogenic risk associated with benomyl's replacements.
|
From page 201... ...
At that time the EPA sought information on the oncogenic, mutagenic, teratogenic, and other reproductive effects of captan. PD 2/3 was issued June 21, 1985, in which the EPA proposed to cancel all uses of captan on food crops unless "data are submitted that demonstrate that actual residues are sufficiently lower than current tolerances or that modification to application practices will sufficiently reduce dietary risk." Special Review Criteria Triggered Oncogenicity Mutagenicity
|
From page 202... ...
Estimate of Dietary Oncogenic Risk Using the multistage model for risk assessment, the EPA has calculated two estimates of dietary oncogenic risk. One is based on residues of captan at tolerance levels; the other is based on data from market basket surveys conducted by Chevron, Stauffer, the FDA, and the Canadian government.4 Using Food Factor consumption estimates assuming that 100 percent of all crops with tolerances for captan are treated and that residues are at the tolerance level, the agency estimates a dietary upper-bound oncogenic risk of 10-3 to 10-4 When market basket survey residue figures are used, the risk is calculated at 10-6 to 10-7.
|
From page 203... ...
Although the residue data cited above6 indicate that captan residues generally decline with the processing of foods, it is possible that residues could concentrate in animal feed portions of many crops, thus necessitating section 409 feed additive tolerances for these crops. If tolerances were denied or revoked because of the concentration of residues in animal feeds, significant adjustments would be required of growers highly dependent on captan.
|
From page 204... ...
Special Review Criteria Triggered Oncogenicity Summary of Oncogenic Findings and Risk Estimation Evidence of oncogenicity was found in an 18-month feeding study in which male mice exhibited a statistically significant increase in liver tumors when fed chlorobenzilate. An NCI study also found statistically significant increases in total tumors and hepatocellular carcinomas in mice.
|
From page 205... ...
The principal alternative pesticides are ethion, carbophenthion, sulfur, and dicofol. Dicofol is currently under special review and the remaining are in the registration standard process with no evidence of oncogenic effects.
|
From page 206... ...
Oncogencity data are due in October 1987. Special Review Criteria Triggered None Oncogenic Contaminants and the Delaney Clause Animal studies submitted to the EPA do not show dicamba to be oncogenic.
|
From page 207... ...
, and because there is presently no known safe level of exposure to an oncogen, then section 409 tolerances for dicamba cannot legally be issued under the general safety clause. On the other hand, the FDA argues that, using a set of conservative assumptions, exposures that create an additional oncogenic risk of less than 1 in 1 million (1 x 10-6)
|
From page 208... ...
Although the comparative risks of these two compounds were not discussed in the Federal Register notice establishing this tolerance, the EPA's fact sheet and the registration standard document both note that "The performance of dicamba containing herbicides is such that they are viable alternatives to the suspended uses of silvex and 2,4,5-T." One result of this use of the constituents policy was to provide an alternative to 2,4,5-T and silvex which, although not risk free, clearly presented less risk. In this way the constituents policy provided a mechanism to move toward the use of safer pesticides.
|
From page 209... ...
No feed additive tolerances have been established for the many EBDC-treated vegetable and fruit by products that are used as animal feed. No tolerances have been established for ETU—a contaminant con version product and metabolite of the EBDCs.
|
From page 210... ...
These studies found · Increased lung adenomas in three short-term (6- to 11-week) single-dose EBDC feeding studies with mice; · Increased liver and lung tumors and lymphomas in mice fed a single dose of ETU for 80 weeks; · Thyroid carcinomas in both doses of an 18-month ETU feeding study of rats; and · Dose-related thyroid carcinomas, thyroid adenomas, and thyroid hyperplasia during a 2-year ETU feeding study of rats.
|
From page 211... ...
When exposure to ETU residues through metabolism of EBDC residues calculated at survey levels or the level of detection were added to the lowest-case estimate, the dietary exposure level was calculated as 3.4 x 10-4, or an additional 0.00010 mg/kg body weight/day. Risk Assessment Using the one-hit model, oncogenic risks from dietary exposure were calculated for both a worst-case and a lowest-case estimate.
|
From page 212... ...
The agency has stated that it may have underestimated the upper limit on risk because of inadequate data on animal metabolism, ETU in processed foods, residues on raw agricultural commodities, and residue in drinking water, meat, milk, eggs, and animal feeds. Tolerance and Delaney Clause Issues Specific issues include · Prior sanctioned tolerances; · Readjustment of section 408 tolerances in 1972; · Conversion of EBDCs to ETU, and thus ETU concentration during cooking, canning, and other processing; · Absence of sections 408 and 409 tolerances for ETU; · Absence of section 409 feed additive tolerances for many vegetable and fruit by-products; and · Absence of tolerances for milk, meat, and eggs, even though EBDCs are applied to numerous commodities used as animal feed, and ETU has been detected in those foods.
|
From page 213... ...
However, where conversion takes place, the ETU residues in processed foods will be greater than the ETU levels in the raw agricultural commodity. In other words, ETU is an oncogenic by-product of an oncogenic pesticide, concentrating to levels in processed foods that are not likely to exceed the relatively high section 408 tolerances for the EBDCs that for enforcement purposes are applied to ETU; but ETU residues are potentially higher in processed foods than they are in raw agricultural commodities.
|
From page 214... ...
It is noteworthy, however, that many of these crops have no processed form, and thus remain beyond the scope of the tolerancesetting limitations of the Delaney Clause. METALAXYL Description of the Chemical Common name: Metalaxyl Trade name: Ridomil Pesticide type: Systemic fungicide Chemical family: Benzenoid Year registered: 1979, conditional registration Major producer: Ciba-Geigy, under patent Volume of use: Approximately 400,000 pounds were used on tobacco in 1982.
|
From page 215... ...
Special Review Criteria Triggered Issues of oncogenicity were dealt with in the registration process. Summary of Oncogenic Findings Chronic rat feeding studies to support the registration of metalaxyl were initially accepted, and the determination was made that the fungicide was not an oncogen.
|
From page 216... ...
Using a risk estimation derived from this statistical analysis, the EPA staff have calculated eight upper limits of oncogenic risk from dietary exposure ranging from 2.41 per 10,000 (2.41 x 10-4)
|
From page 217... ...
No section 409 tolerances have been issued because of oncogenicity and the Delaney Clause. Regulatory Status General-use pesticide Special Review Criteria Triggered Positive findings of oncogenicity in mice were dealt with in the registration process.
|
From page 218... ...
For enforcement purposes, it was deemed impossible to determine whether any portion of the treated raw agricultural commodity would be present in any processed food or animal feed. Permethrin was granted a section 408 tolerance, however, for use only on "Tomatoes Grown in Florida for Final Marketing as Fresh Tomatoes." By prohibiting the use of permethrin on tomatoes for processing, the Delaney Clause was not invoked.
|
From page 219... ...
Because no waste will be fed to animals, no section 408 tolerances for meat, milk, or eggs were deemed necessary. CORN Tolerances were initially proposed for residues of permethrin and its metabolites in or on the following raw agricultural commodities: corn fodder at 5 ppm, corn forage at 12 ppm, and corn grain at 0.05 ppm.
|
From page 220... ...
THIODICARB Description of the Chemical Common name: Thiodicarb Trade name: Larvin Pesticide type: Insecticide Chemical family: Carbamate Year registered: 1979 Major producer: Union Carbide, under patent Volume of use: Not available Tolerances: A section 408 tolerance of 2.0 ppm for thiodicarb residues in sweet corn was established in 1984. Sections 408 and 409 tolerances for thiodicarb and its metabolite methomyl in or on cotton, cotton seed, soybeans, and soybean hulls were initially denied under the Delaney Clause.
|
From page 221... ...
On the basis of this body of evidence and these presumptions, the EPA calculated an upper-bound estimate of total dietary oncogenic risk from acetamide in the diet as a result of thiodicarb residues on cotton and soybeans, of approximately 1 x 10-6. Yet, it is clear that the agency does not believe that the dietary risks are this high.
|
From page 222... ...
Until concentrating oncogenic residues of methomyl and/or its metabolites are detected, the Delaney Clause will not apply to methomyl, regardless of its chemical similarity to thiodicarb. Tolerance and Delaney Clause Issues Because thiodicarb is known to concentrate in cotton seed and soybean hulls, its use on soybeans and cotton requires section 409 feed additive tolerances.
|
From page 223... ...
Sensitivity-of-the-Method Procedure Because acetamide is an animal metabolite of thiodicarb, and not present in foods derived from soybeans and cotton treated with thiodicarb, the setting of animal feed additive tolerances under section 409 of the FDC Act is the focal point of this exercise. Within section 409(c)
|
From page 224... ...
In contrast, the maximum expected acetamide levels in milk and eggs resulting from thiodicarb residues on cottonseed and soybean hulls are 0.3 and 0.07 ppb, respectively. Union Carbide requested a waiver from the requirement for an analytical method of detection because milk and egg samples purchased at grocery stores in 11 states contained levels of 275-500 ppb acetamide for milk, and 75-350 ppb acetamide for eggs far above anticipated maximum residues from use of thiodicarb as well as those equivalent to a risk of 1 x 10-6 (30 and 90 ppb)
|
From page 225... ...
Chaisson, U.S. Environmental Protection Agency, regarding correction of worst-case dietary exposure to benomyl in the United States for percent crop tracked and direct sampling of selected crops in a Du Pont market booklet survey.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.