Dietary Risk Assessment of the Organophosphate Insecticide

Chapter 13

Downloaded by UNIV OF TEXAS SAN ANTONIO on October 9, 2015 | http://pubs.acs.org Publication Date: March 8, 2005 | doi: 10.1021/bk-2005-0899.ch013

Dietary Risk Assessment of the Organophosphate Insecticide/Acaricide Methamidophos Derek W. Gammon, Wesley C. Carr, Jr., and Keith F. Pfeifer Medical Toxicology Branch, Department of Pesticide Regulation, Cal/EPA, Sacramento, CA 95812

A toxicological profile of methamidophos was integrated into two computer models, (TAS and DEEM ) to calculate dietary margins-of-safety (MOSs) for cotton, potato and tomato. No Observed Effect Level(s) (NOELs) of 0.3 mg/kg/day (rat, acute) and 0.02 mg/kg/day (dog, estimated chronic), for brain AChE inhibition, were used. Crop residue data were employed to estimate exposure/MOSs for 20 population sub-groups. Deterministic (point estimate) and probabilistic (Monte Carlo) simulations compared acute exposure (95 percentile) using two consumption databases. Chronic exposures/MOSs were calculated using annualized means. Acute and chronic MOSs were >100 for all population sub-groups, which is generally considered adequate. For residues at tolerance, acute MOSs were above 100 for cotton and potato, but only 34 to 94 (DEEM /TAS ) for tomato. ®

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Note: The opinions expressed are the authors' and do not necessarily reflect the policies of Cal/EPA.

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© 2005 American Chemical Society In Environmental Fate and Safety Management of Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

139 Methamidophos was developed in the mid-1960s, controlling insects and mites in a range of vegetable crops. It was also used on non-food crops such as alfalfa, clover, Bermuda grass, cut/outdoor flowers and in greenhouses. It has high acute toxicity (USEPA Category 1), with L D values ~15 mg/kg (rat, oral) and ~100 mg/kg (rabbit, dermal). It acts by inhibiting acetylcholinesterase (AChE), in insects and mammals. In 1996, following concerns about occupational safety, all (13) registrations except cotton, potato and tomato were voluntarily canceled by Bayer, the principal registrant. In California, methamidophos usage fell from 500,000 (1995) to 47,000 lbs. (2001). In 2002, an IRED (Interim Reregistration Eligibility Document) (1) and a Risk Management Decision Document (2) were issued for methamidophos by USEPA. The main conclusions were: 1/ dietary exposure to methamidophos did not require mitigation, 21 cotton uses were to be discontinued by 2007, with three mitigation issues: a) monitoring data were to be collected to address possible surface water contamination (as calculated using PRZM-EXAMS and GENEEC models); b) engineering controls were needed to reduce worker exposure; c) ecological risks to birds and mammals were excessive but would be mitigated by removing cotton uses. Further, this IRED was "interim" pending the evaluation of acephate, an organophosphate (OP) that is toxic only after conversion to methamidophos, and other insecticides, under a "cumulative" risk assessment, as required by the Food Quality Protection Act (FQPA) (3). Because such a complete database is available for methamidophos, USEPA has chosen it as the "Index Chemical" for the relative potency factor (RPF) approach that it proposes to adopt in its cumulative OP risk assessment (4). Paradoxically, under the terms of the IRED, tolerances for cottonseed were increased from 0.1 ppm to 0.2 ppm, for tomato from 1 ppm to 2 ppm and potato, to remain at 0.1 ppm.


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Risk assessment for a chemical is a function of toxicity and exposure. As such, toxicity is determined in a series of studies and from these, no observed effect levels (NOELs) are chosen to represent acute and chronic toxic effects. The key studies are described in detail. Dietary exposure, in turn, is a function of two parameters, Le. the pesticide residue in the treated crop and the amount of treated food consumed by a person. Computer models have been developed to estimate dietary exposure to pesticides and two of these are compared, TAS (5) and DEEM (6). Both programs divide the US population into groups, based principally on age, gender and ethnicity. They make use of USDA surveys known as CSFII - Continuing Surveys of Food Intake by Individuals. The two surveys used here cover the years 1989-1992 and 1994-1996, 1998. The later CSFII was conducted around the time that FQPA was passed (1996) and is biased towards collecting more data on infants and children. The programs model dietary exposure in two ways. First, a deterministic (point estimate) model was used, which assumes that the crop contains a specific amount of pesticide contamination. This value is based on crop residue studies and is generally chosen to be at the 95 percentile of the available residue data. ®

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In Environmental Fate and Safety Management of Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

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Secondly, a probabilistic (Monte Carlo) simulation was used. This considers a complete set of crop residue data and samples data points randomly. This approach is generally considered to be more "realistic" for assessing dietary exposure to a pesticide. Tolerance assessments used TAS® and DEEM® in order to establish the safety of tolerances (MRLs or maximum residue limits) for cotton, potato and tomato and also to compare the output of the two programs.

Environmental Fate Methamidophos has low persistence in soil (t. values of < 4 days). It is highly hydrophilic (logKo = -0.66) (7), is weakly adsorbed by soil with a high potential to leach but, because of its rapid breakdown, it is unlikely to leach in practice. In California, there have been no detections of methamidophos in groundwater monitoring studies. It has a high vapor pressure, but because of its high water solubility, it has a low Henry's Law constant, thus giving it a low tendency to volatilize under field conditions. The results of crop residue studies are summarized in Table I. /a

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Table I. Summary of Methamidophos Crop Residue Data. Raw Agricultural Tolerance, Commodity (RAC) ppm Cottonseed, meal*' 0.1 (N) eJ/

Cottonseed, oil" c/

Potato

0.1 ( Ν / ' 0.1 (Ν)

%-Crop treated Residue Residue (%CT) acute, ppm** chronic, ppm 0.042(N) 15% 0.044 (n=32) 0.01 (n=4)

0.005

15%

0.0091 (n=1401)

0.0019

30%

20% (processed) 0.013 0.082 (n=849) 1" 85% (fresh) a/ Pre-harvest Interval: 7 days, tomato, 14 days potato and 50 days, cottonseed; (n=number of composite samples analyzed) b/ from Bayer, the primary registrants; LOQ = 0.01 ppm c/ from USDA - PDP program, 1994-5; Limit of detection (LOD) = 0.003 ppm d/ from USDA - PDP program, 1996-7; Limit of detection (LOD) = 0.001 ppm e/ negligible residue îl tolerance increased to 0.2 ppm in (7). g/ tolerance increased to 2 ppm in (7).

Tomato*

In Environmental Fate and Safety Management of Agrochemicals; Clark, J., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 2005.

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Toxicology Profile


Chronic Toxicity and Oncogenicity Summary: Methamidophos given in the diet for periods of one or two years, resulted in body weight loss in the rat and mouse, but not the dog. There was an increase in relative brain weight at the highest dose tested (HDT) in these rodents, in both sexes, but not in the dog. There were few clinical signs and no evidence of oncogenicity. In all three species, inhibition of AChE in plasma (which also includes butyryl cholinesterase), red blood cell (RBC) and brain was reported. The LOEL for inhibition of brain AChE was 2 ppm, equivalent to 0.1, 0.3 or 0.06 mg/kg/day in the rat, mouse and dog, respectively. An estimated NOEL of 0.02 mg/kg/day, after 11-18% inhibition of brain AChE at 0.06 mg/kg/d in a 1-yr. dog study, was the critical one selected for chronic risk characterization. The use of an uncertainty factor of 3 (rather than 10) in calculating an estimated NOEL from a LOEL was supported by Benchmark Dose (BMD) calculations. In the critical study, methamidophos was fed to beagle dogs (6/sex/level) at 0, 2, 8, or 32 ppm (0, 0.06, 0.24 or 0.90 mg/kg/day, M and 0, 0.06, 0.22 or 0.88 mg/kg/day, F) for 1-yr (8). Mean body weight was not significantly affected by treatment. There was increased lacrimation at 8 and 32 ppm, significant (p

Dietary Risk Assessment of the Organophosphate Insecticide

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