Non-Hodgkin's Lymphoma and Specific Pesticide Exposures in Men; Mechanism of inhibition of lysyl hydroxylase activity by the organophosphates malathion and malaoxon; Cytogenetic studies on the effect of feeding mice with stored wheat grains treated with malathion;
Subject: Sound Science is not an oxymoron..............
Date: Sat, 29 Dec 2001 10:49:43 -0500
From: Stephen Tvedten <steve@getipm.com>
Organization: Get Set Inc. (www.getipm.com)
To: Paul Helliker <phelliker@cdpr.ca.gov>
Director, State of
California, Department of Pesticide Regulation
cc: Christine Whitman whitman.christine@epa.gov
Dear Mr. Helliker, I thought you might like to read some more unbiased research on your "registered" POISONS:
1: Cancer Epidemiol Biomarkers Prev 2001 Nov;10(11):1155-63 http://www.ncbi.nlm.nih.gov:80/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11700263&dopt=Abstract</A>
Non-Hodgkin's Lymphoma and Specific Pesticide Exposures in Men: Cross-Canada Study of Pesticides and Health.
McDuffie HH, Pahwa P, McLaughlin JR, Spinelli JJ, Fincham S, Dosman JA, Robson D, Skinnider LF, Choi NW. Centre for Agricultural Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, S7N 0W8 [H. H. M., P. P., J. A. D.].
Our objective in the study was to investigate the putative associations of specific pesticides with non-Hodgkin's Lymphoma [NHL; International Classification of Diseases, version 9 (ICD-9) 200, 202]. We conducted a Canadian multicenter population-based incident, case (n = 517)-control (n = 1506) study among men in a diversity of occupations using an initial postal questionnaire followed by a telephone interview for those reporting pesticide exposure of 10 h/year or more, and a 15% random sample of the remainder. Adjusted odds ratios (ORs) were computed using conditional logistic regression stratified by the matching variables of age and province of residence, and subsequently adjusted for statistically significant medical variables (history of measles, mumps, cancer, allergy desensitization treatment, and a positive history of cancer in first-degree relatives). We found that among major chemical classes of herbicides, the risk of NHL was statistically significantly increased by exposure to phenoxyherbicides [OR, 1.38; 95% confidence interval (CI), 1.06-1.81] and to dicamba (OR, 1.88; 95% CI, 1.32-2.68). Exposure to carbamate (OR, 1.92; 95% CI, 1.22-3.04) and to organophosphorus insecticides (OR, 1.73; 95% CI, 1.27-2.36), amide fungicides, and the fumigant carbon tetrachloride (OR, 2.42; 95% CI, 1.19-5.14) statistically significantly increased risk. Among individual compounds, in multivariate analyses, the risk of NHL was statistically significantly increased by exposure to the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D; OR, 1.32; 95% CI, 1.01-1.73), mecoprop (OR, 2.33; 95% CI, 1.58-3.44), and dicamba (OR, 1.68; 95% CI, 1.00-2.81); to the insecticides malathion (OR, 1.83; 95% CI, 1.31-2.55), 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (DDT), carbaryl (OR, 2.11; 95% CI, 1.21-3.69), aldrin, and lindane; and to the fungicides captan and sulfur compounds. In additional multivariate models, which included exposure to other major chemical classes or individual pesticides, personal antecedent cancer, a history of cancer among first-degree relatives, and exposure to mixtures containing dicamba (OR, 1.96; 95% CI, 1.40-2.75) or to mecoprop (OR, 2.22; 95% CI, 1.49-3.29) and to aldrin (OR, 3.42; 95% CI, 1.18-9.95) were significant independent predictors of an increased risk for NHL, whereas a personal history of measles and of allergy desensitization treatments lowered the risk. We concluded that NHL was associated with specific pesticides after adjustment for other independent predictors.
PMID: 11700263 [PubMed - in process] 1: Toxicol Appl Pharmacol 2001 Nov 1;176(3):181-6
Mechanism of inhibition of lysyl hydroxylase activity by the organophosphates malathion and malaoxon.
Samimi A, Last JA.
Pulmonary/Critical Care Medicine, University of California, Davis, California, 95616
Direct inhibition of lysyl hydroxylase by malathion and malaoxon was observed in an in vitro enzyme assay with recombinant lysyl hydroxylase expressed via a baculoviral system. The IC50 values for malathion and malaoxon were estimated to be approximately 60 and 45 mM, respectively. Additional kinetic studies showed this inhibition to be competitive or partially competitive with respect to the synthetic (collagen) peptide, partially uncompetitive with respect to Fe(2+), and partially noncompetitive with respect to ascorbic acid. The calculated values for the K(i) were consistent with the IC50 values. Allosteric effects were not found for any of the cofactors tested, the peptide substrate, or the inhibitors. Interactions were found to be unimolecular for lysyl hydroxylase and its substrate and cofactors as well as for the inhibitors malathion and malaoxon. A computer search of a protein structure database showed an unexpected region of partial homology between the active site sequence of acetylcholinesterase and a segment of lysyl hydroxylase, suggesting a possible molecular basis for these observations. These results suggest the possibility of a novel and hitherto unexpected class of inhibitors of lysyl hydroxylase, based on the organophosphate structure, that might be of value for testing as antifibrotic drugs. Copyright 2001 Academic Press.
PMID: 11714250 [PubMed - in process] ------------------------------------------------------------------------
Cytogenetic studies on the effect of feeding mice with stored wheat grains treated with malathion.
Amer SM, Fahmy MA, Aly FA, Farghaly AA.
Department of Genetics and Cytology, National Research Center, Dokki, Cairo, Egypt
The cytogenetic effect of malathion residues in wheat grains stored for different periods of time (4, 12, 24 weeks) was evaluated in Swiss mice. The studies included: (1) chromosomal aberrations analysis in bone-marrow and spermatocyte cells; (2) chromosomal aberrations and sister chromatid exchange (SCE) analysis in spleen cell culture from mice fed with stored wheat grains. The tested doses were 8.36 (applied dose), 25.08 and 41.80mg malathionkg(-1) wheat grains. The results demonstrated that the cytogenetic effect induced in different mouse tissues by malathion residues was dose-dependent and increased with increasing of both feeding and storage periods.Feeding mice with wheat grains stored for 4 weeks had a non-significant effect with respect to the induction of chromosomal aberrations or SCEs. Significant chromosome damage and increase of SCEs were observed in mice fed with wheat grains stored for 12 weeks. The maximum effect was recorded in mice fed for 12 weeks with the grains treated with the highest tested dose and stored for 24 weeks. However, mitomycin C i.p.-injected in mice at 1mgkg(-1) body weight (b.w.) (positive control) induced a higher effect. The percentage of chromosome aberrations reached 13.60+/-0.98, 13.60+/-0.77 and 11.73+/-0.98 (P<0.01) in bone-marrow, cultured spleen cells and spermatocytes, respectively. The significant increase of abnormalities in spermatocytes was seen for univalent formation only, predominantly of the sex chromosomes. The frequency of SCEs was 10.76+/-0.62 per cell (P<0.01) in cultured spleen cells compared with 5.46+/-0.45 per cell for control and 14.66+/-0.54 per cell for the positive control.The obtained results indicate that malathion residues in stored wheat grains have potential genotoxic effect in mice under the conditions tested.
PMID: 11719084 [PubMed - in process]
Well Mr. Helliker, Helen Keller once said: "The greatest tragedy in life is people who have sight but no vision." How much more scientific proof will it take, before you will be able to envision the absolute necessity, that you should allow the use of safe, far more effective and economical (unregistered) alternatives to actually solve pest problems?
Respectfully. Stephen L. Tvedten
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