Shift in FTIR spectrum patterns in methomyl-exposed rat spleen cells.

Methomyl is a highly toxic carbamate insecticide which is widely used in many agricultural countries. We have applied the Fourier-transformed infrared (FTIR) spectroscopic method to study the toxicity of methomyl on cytoskeletal protein and the nucleic acid of rat spleen cells. Rats were given methomyl by gavage at 2, 6 and 8 mg/kg in single doses. Colchicine, a microtubule-disrupting agent, was given to rats at 2, 4, and 6 mg/kg in single doses and mitomycin C, an alkylating agent which acts as a DNA-cross-linking agent, was given by an intraperitoneal route to rats at 1 mg/kg. It was shown that the wavenumber of FTIR spectra at amide I and amide II in both methomyl- and colchicine-exposed rats shifted in dose response manner when compared with the control (P < 0.05). The amide I and II shifts in these regions have been proposed to be the result of an alpha-helix protein conformational change. Toxic doses of mitomycin C, a DNA-cross-linking agent, did not result in this pattern. Moreover, all exposed rats showed an increase in the absorbance ratios that were related to the vibrational mode of the phosphodiester group in nucleic acid (P < 0.05).

Increase in tumour necrosis factor-alpha and a change in the lactate dehydrogenase isoenzyme pattern in plasma of workers exposed to aflatoxin-contaminated feeds.

Six types of animal-feed ingredients and swine mixed feeds from factories in northern Thailand were sampled for analysis of mycotoxins. Mycotoxins found in foodstuffs included aflatoxins, fumonisins, ochratoxins, T-2 toxin, vomitoxin and zearalenone. Samples of airborne dust generated while handling animal feed were collected and analysed to assess exposure of workers to aflatoxins. The average aflatoxin level in the control air samples was 0.99 ng/m3. Higher levels of aflatoxins were found in the air samples taken by samplers attached to five workers adding hydrated sodium calcium aluminosilicate to animal feed (group 1; 1.55 ng/m3) and five workers adding glucomannan to animal feed (group 2; 6.25 ng/m3). The exposed workers showed a change in lactate dehydrogenase isoenzyme activity and tumor necrosis factor-levels in plasma. These changes may be associated with inhalation of mycotoxins and other contaminants in foodstuff. Occupational exposure to mycotoxins and mycotoxin adsorbents needs further evaluation in order to set up a proper system for long term surveillance of exposed population.

Accreditation of analytical laboratories and proficiency testing: experiences from Thailand on the issues of pesticide analysis.

Thailand, the economic growth of which largely depends on agriculture-based industry, recognizes the importance of international standards for harmonization of international food trade and for protection of human health from chemicals used as food additives or those present as contaminants. Pesticides which are widely used in Thailand are the anticholinesterase pesticides, pyrethroids, coumarin derivatives, bipyridinium salts, and to some extent organochlorine compounds such as DDT in malaria control. Proficiency testing and accreditation of laboratories are recognized as effective means to ensure quality and validity of data and to enable adequate risk assessment of pesticide residues in food, work environment and environment in general. The paper is a synthesis of relevant local reviews and in-depth interviews with experts in the area of pesticide laboratory accreditation and proficiency testing. The paper refers to other schemes for quality assurance such as ISO guide 25, ISO 9000, and ISO 14000, and addresses future prospects of ongoing activities such as accreditation of inspection bodies in the area of industrial chemicals and occupational safety and health.

Toxicokinetics and safety factors in risk assessment.

For risk assessment of anticholinesterase pesticides, acetylcholinesterase inhibition is a sensitive, reversible indicator of exposure. However, use of smaller factors when data are available in human may not be justified in some specific cases. Direct action of anticholinesterase on receptor sites at various cell types in different target organs may yield to the more severe nature of toxicity. At the present time, uncertainties exist due to our limited capability to clarify many human diseases with complex etiology. The toxicokinetic models available may not accommodate some type of toxicants which their mode of action involve haemodynamic change or vascular cell injury. Anticholinesterase pesticides are still widely used in many asian countries to control a variety of pest species in agricultural practices. The physiology of the effects of these agents are complex and appropriate uncertainty or "safety factors" are needed to be acknowledged and taken into account from total exposure. Risk assessment of anticholinesterase agents is related to complex biological system and we will probably, never, at least in our lifetimes, know everything we would like to know to assess risk. We can only do our best with current information available. However, one should be extremely careful and holistic when applying these uncertainties in risk assessment of anticholine-esterase pesticides.

Increase in lactate dehydrogenase isoenzyme-4 and splenocyte toxicity in methomyl-treated rats.

The toxic effect of methomyl was studied in rats after a single or repeated oral administration. Rats treated with a single dose of methomyl (3, 5, or 7 mg/kg) showed significant increase (P < 0.05) in total lactate dehydrogenase (LDH) activity on day 1. The highest level of LDH activity was observed on day 3 in rats receiving 7 mg/kg of methomyl. The total LDH activity returned to normal on day 7 after dosing. Specific increases in LDH-3 and LDH-4 isoenzyme activities were observed. In rats treated with a single dose of 6 and 8 mg/kg of methomyl, spleen weight and splenocyte viability significantly dropped (P < 0.05) on days 1 and 3, respectively. Splenotoxicity was prevented by pretreatment with 60 mg/kg of N-acetylcysteine. The results suggest that the splenotoxic effect of methomyl is more likely directly related to oxidative cell injury than to cholinesterase inhibition. The significance of cytotoxic effects and the nature of cytotoxicity in relation to reactive oxidative damage deserve further investigation.

Exposure evaluation is a crucial step for quantitative risk assessment of methomyl.

Methomyl, methyl N-[[(methylamino)carbonyl]oxy]ethanimidothioate is a carbamate insecticide with anticholinesterase activity. As a broad spectrum insecticide, it is one of the most frequently used pesticides in tangerine orchards in Thailand. Although methomyl is said to be rapidly eliminated from experimental animals (1) high incidence of acute poisonings was reported among patients occupationally exposed to a powder formulation of methomyl (2, 3). In this passive dosimetry study of tangerine growers, during mixing and overhead spraying of a 90% powder formulation of methomyl, ocular and nasal exposure was measured. Exposure data are discussed in terms of the "potentially absorbed" or "internal dose".

Respiratory effects of hexachlorocyclopentadiene on intact rainbow trout (Salmo gairdneri) and on oxidative phosphorylation of isolated trout heart mitochondria.

Acclimated normal rainbow trout were exposed to 130 ppb hexachlorocyclopentadiene (HEX) in a flow-through well water circuit which was designed to permit measurements of oxygen consumption by the fish. Compared to preHEX values, HEX increased oxygen consumption rates by 186 +/- 24% (means +/- SEM), with maximum oxygen consumption rates being reached in approximately 84 min after HEX exposure. Oxygen consumption subsequently decreased, and all HEX-exposed fish died within 6.5 hr of exposure. Fish exposed to HEX-free vehicle (acetone) showed no changes of oxygen consumption. When added to normal isolated trout heart mitochondria, HEX appeared to uncouple oxidative phosphorylation, with calculated respiratory control ratios being decreased 50% from control values at a HEX concentration of 0.41 microM. We postulate that one important mechanism of HEX intoxication in the intact animal may be due to increased oxygen consumption and impaired oxidative ATP synthesis due to the mitochondrial uncoupling action of the toxicant.