Diazinon toxicity tests

The effect of dietary protein on diazinon toxicity was evaluated in a study with male albino Wistar rats. The study concluded that a purified protein test diet (with 26% casein and 59% cornstarch) did not significantly alter the LD50 value (415 mg/kg) for diazinon for this species. However, a low protein purified test diet (3.5% casein, 82% cornstarch), lowered the LD50 to 215 mg/kg. In addition, this study found that diazinon samples that were time-of-manufacture stabilized (to prevent spontaneous degradation to more toxic monothiotetraethyl pyrophosphate) were less toxic (LD50 value = 466 mg/kg) than samples stabilized after manufacture (LD50 value = 271 mg/kg) (Boyd and Carsky 1969). A subsequent study... 

Two female Beagle dogs received a single intravenous dose of 0.2 mg/kg [14C]diazinon in ethanol. Radioactivity in the blood decreased in a biphasic manner. The half-life of the terminal or elimination phase was estimated to be 15 hours (Iverson et al. 1975). Diazinon was found (5 mg/kg) in omental fat of a man found unconscious and who died 11 days later (Kirkbride 1987). Pesticide exposure was suspected in his death but no confirmatory test of acetylcholinesterase activity was performed, nor were clinical signs of diazinon toxicity reported. This man worked at a horticultural supply store and was an active gardener, however no route of exposure to the diazinon could be confirmed. 

The rat (Rattus rattus) was the most sensitive mammal tested in acute oral toxicity screenings, with an LD50 of 224,000.0 tig diazinon/kg BW. Chronic oral toxicity tests with swine (Sus scrofa) indicated that death was probable if daily intakes were greater than 5000.0 xg diazinon/kg BW. Measurable adverse effects of diazinon have been recorded... 

The diazinon dose that causes death of experimental animals depends on the form of the test compound (pure, technical, or formulated preparations) as well as on the animal species, sex, and age, and other modifying factors such as diet. It is likely that earlier formulations were more toxic to experimental animals than current ones because of the formation of toxic breakdown products (e g., sulfotepp) in unstabilized diazinon (Hayes 1982). 

Genotoxicity. Chronic occupational exposure to multiple insecticides, including diazinon, has been associated with an increased incidence of chromosomal aberration and increased sister chromatid exchange in peripheral blood lymphocytes in these individuals (de Ferrari et al. 1991 Kiraly et al. 1979 See et al. 1990). The results from these studies are confounded by either concurrent or sequential (or both) exposures to other unknown toxic substances, mainly other insecticides, that may be genotoxic. No in vivo genotoxicity studies in laboratory animals were located for diazinon. The results of in vitro tests in... 

Experimental design (human study details or strain, number of animals per exposure/control group, sex, dose administration details) The purpose of this study was to determine the 13-week oral toxicity profile of diazinon in male and female beagle dogs. Diazinon was added to standard canine ration at concentrations of 0, 0.1, 0.5, 150, and 300 ppm. The test substance was the MG-8 formulation of diazinon (87.7% pure) mixed with feed and adjusted for purity. The concentrations of diazinon in the feed were determined during weeks 1, 3, 5, 9, and 13. Each dog was supplied with approximately 400 g of food daily. The corresponding doses, in mg/kg, were calculated by the authors to be 0.0034, 0.02, 5.9, and... 

The hydroxypyrimidine hydrolysis product of diazinon is more readily available in all soils tested and is mineralized by microbes (33). Our Microtox studies have demonstrated its low toxicity to bacteria. Availability, low microbial toxicity, and susceptibility to microbial metabolism of this hydrolysis product may favor enhanced degradation of its parent compound in soils with populations of degrading microorganisms, but no adaptation was noted in our laboratory studies. 

The toxicity of a chemical also varies from one animal to the next. The LD50 for the common insecticide Diazinon is 300 to 400 mg/kg in rats, while in birds it is 2.75 mg/kg. Theobromine, a chemical found in chocolate, is toxic to dogs but not to rodents. Although largely extrapolated from animal tests, a rating system for acute chemical toxicity for humans has been devised and is presented in Table 1. 

A recent study of Moser eoworkers (2005) Mo,ser et uL (2005), using a do.se-additive design with mixtures of five commonly used OP pesticides (chlorpyrifos, diazinon, dimeihoate, acephaic, and malathion), showed a more-than-additive interaction on multiple end points blood and brain cholinesterase inhibition, motor activity, and gait score (tail-pinch response did not. show a more-than-additive interaction). This study is noteworthy because (i) relatively sensitive end points were used to test the toxic interaction of the OP pesticides, such as cholinesterase inhibition or depression of motor activity (ii) more than two OP compounds were used in the mixture and (iii) comprehensive statistical analyses of the data were performed. The pharmacokinetic interaction of two of the aimpounds in the mixture, chlorpyrifos and diazinon, has been studied in rats (Timchalk et a ., 2004). The authors found that one compound did not affect the pharmacokinetics of the other unless high doses were given, concluding that a more-than-additive interaction is unlikely at environmentally relevant concentrations. 

Many plant metabolites marketed as natural pesticides are in fact more toxic than their synthesized competitors for example, rotenone (extracted from the roots of certain members of the bean plant family) has been used as a crop insecticide since the mid-19th century to control leafeating caterpillars, but is six times more toxic to mammals on a strictly comparable basis than carbaryl, a synthetic chemical also effective for caterpillar control. Nicotine sulfate is extracted from tobacco by steam distillation or solvent extraction and has been used as a pesticide since the early 20th century it is six times more toxic than diazinon, a widely available synthetic insecticide sold for control of many of the same pests. The best known work in this area (Ames 1990, 1990a, 1997) used the Ames test (Ames 1973, 1973a) to compare potencies of natural and synthetic pesticide compounds with respect to mutagenicity in special bacterial strains. While some of the conclusions of this work are controversial (Tomatis 2001), it does at least emphasize the importance of development of analytical methods for natural as well as synthetic compounds in foodstuffs. In this section an example of each is considered. 

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