Histopathological lesions, oxidative stress and genotoxic effects in liver and kidneys following long term exposure of rabbits to diazinon and propoxur.

PURPOSE: The aim of the present study was to investigate the effects of diazinon and propoxur on liver and kidneys, following long term exposure of rabbits. METHODS: Ten New Zealand white female rabbits were used. The animals were divided into 5 groups, consisting of 2 animals each. Diazinon (groups 1 and 2) and propoxur (groups 3 and 4) were administered at 2 different doses, and group 5 served as the control group. Histopathological lesions in the liver and kidneys, oxidative stress and oxidative DNA damage were evaluated. RESULTS: Both pesticides induced focal inflammation and fibrosis in the liver and kidneys. The low dose of propoxur induced a significant increase in total antioxidant capacity (TAC), with no difference in reduced glutathione (GSH), while the high dose of propoxur induced an increase in GSH with no change in TAC. For diazinon-exposed animals, the opposite findings were observed. Both diazinon and propoxur induced a statistically significant oxidative DNA damage in the liver and kidneys and a subsequent increase in telomerase activity in these tissues, possibly as a counteracting mechanism. Furthermore, systemic inflammation, as depicted by the dose-dependent increase in telomerase activity in peripheral blood mononuclear cells (PBMCs), was observed in propoxur treated animals. CONCLUSIONS: Histopathological lesions, oxidative stress and genotoxic effects were induced in liver and kidneys following long term exposure of rabbits to diazinon and propoxur.

Fetal exposure to propoxur and abnormal child neurodevelopment at 2 years of age.

OBJECTIVE: Our aim was to determine the effects of fetal exposure to propoxur and pyrethroids, on child neurodevelopment at 2 years of age. PATIENTS AND METHODS: Mothers were prospectively recruited during mid-pregnancy in Bulacan, Philippines where multiple pesticides including propoxur, cyfluthrin, chlorpyrifos, cypermethrin, pretilachlor, bioallethrin, malathion, diazinon and transfluthrin are used. To detect prenatal exposure to these pesticides, maternal hair and blood, infant's hair, cord blood, and meconium were analyzed for the pesticides by gas chromatography/mass spectrometry. Infants were examined at 2 years of age with 95.1% follow up rate and their neurodevelopment outcome was assessed by the Griffiths mental developmental scale (N=754). RESULTS: Meconium analysis was the most sensitive method to detect fetal exposure to pesticides and exposure was highest for propoxur (21.3%) and the grouped pyrethroids (2.5% - bioallethrin, transfluthrin, cyfluthrin and cypermethrin). Path analysis modeling was performed to determine the effects of fetal exposure to propoxur and pyrethroids on the child's neurodevelopment at 24 months of age while controlling for confounders. Only singletons and those with complete data for the path analysis were included (N=696). Using a path analysis model, there was a significant negative (ß=-0.14, p<0.001) relationship between prenatal pesticide exposure to propoxur and motor development at 2 years of age after controlling for confounders, e.g., infant gender, socioeconomic status, maternal intelligence, home stimulation (HOME), postnatal exposure to propoxur and blood lead level at 2 years of age. CONCLUSION: At 2 years of age, prenatal exposure to propoxur was associated with poorer motor development in children.

Effects of propoxur on the reproductive system of male rats.

The reproductive toxicity of propoxur (2-isopropoxy-phenyl-N-methylcarbamate), a carbamate pesticide, was investigated in adult male Wistar rats exposed to 0, 1.73, 2.6, and 5.2 mg/kg body weight/day for 90 successive days. Results obtained from this study showed a significant (p < 0.05) concentration-dependent increase in food consumption, relative weights of testis, epididymis and kidneys with maximum effects observed at the highest dose of propoxur (5.2 mg/kg) compared to the control. On the contrary, there was a significant (p < 0.05) decrease in the body weight gain, sperm density, serum and intratesticular total cholesterol concentrations, and intratesticular total proteins in rats treated with propoxur at the dose of 5.2 mg/kg body weight. Propoxur had no significant effect on gestation, fertility and parturition indices, average birth weight, litter size and pups sex ratio of untreated female rats mated with treated males rats. These results suggested that propoxur increased food consumption, relative weight of reproductive and detoxication organs, decreased body weight gain and sperm density per gram of cauda epididymis without affecting the reproductive performances.

Pesticide exposure of non-occupationally exposed subjects compared to some occupational exposure: a French pilot study.

Data about non-dietary exposure to different chemical classes of pesticides are scarce, especially in France. Our objective was to assess residential pesticide exposure of non-occupationally exposed adults, and to compare it with occupational exposure of subjects working indoors. Twenty unexposed persons, five gardeners, seven florists and nine veterinary workers living in Paris area were recruited. Nineteen residences, two greenhouses, three florist shops and three veterinary departments were then sampled. Thirty-eight insecticides, herbicides and fungicides were measured in indoor air with an air sampler for 24 h, and on hands by wiping them with isopropanol-wetted swabs. After extraction, samples were analysed by gas and high-performance liquid chromatography. Seventeen different pesticides were detected at least once in indoor air and twenty-one on the hands. An average of 4.2+/-1.7 different pesticides was detected per indoor air sample. The organochlorines lindane, alpha-endosulfan and alpha-HCH were the most frequently detected compounds, in 97%, 69% and 38% of the samples, respectively. The organophosphates dichlorvos and fenthion, the carbamate propoxur and the herbicides atrazine and alachlor were detected in more than 20% of the air samples. Indoor air concentrations were often low, but could reach 200-300 ng/m(3) in residences for atrazine and propoxur. Propoxur levels significantly differed between the air of veterinary places and other places (Kruskal-Wallis test, p<0.05) and dieldrin levels between residences and workplaces (p<0.05). There was a greater number of pesticides on hands than in air, with an average of 6.3+/-3.3 different pesticides detected per sample, the most frequently detected being malathion, lindane and trifluralin, in more than 60% of the subjects. Maximal levels (up to 1000-3000 ng/hands) were observed either in the general population or in workers, depending on the pesticide. However, no significant difference was observed between workers and general population handwipe pesticide levels. As expected, gardeners were exposed to pesticides sprayed in greenhouses. Florists and veterinary workers, whose pesticide exposure had not been described until now, were also indirectly exposed to pesticides used for former pest control operations. Overall, general population was exposed to more various pesticides and at levels sometimes higher than in occupational places. The most frequent pesticides in residences were not the same as in US studies but levels were similar. These preliminary results need to be confirmed in a greater number of residences from different parts of the country, in order to better assess pesticide exposure of the general population and its influencing factors.

Consideration of individual susceptibility in adverse pesticide effects.

The modern environmental awareness leads to the realisation that the human metabolism is stressed by a huge number of chemical substances. Generally, these background exposures, consisting predominantly from natural and partly from industrial as well as life style sources, are tolerated without any adverse effects. Pesticides are chemicals intentionally introduced to the environment and have become necessities in modern agriculture as well as in indoor pest control. Their residues, therefore, is attracting more and more concern. For the majority of pesticides neither occupational nor environmental medical risk evaluations are so far available. Therefore, at the moment the occupational as well as the environmental supported preventive concept may only be achieved, if binding instructions upon experience and guide values are developed for the assessment of the individual risk of handling pesticides. In the occupational and environmental pesticide prophylaxis the ubiquitous background exposure levels in consideration with individual susceptibility factors should be recommended as provisional biological tolerance guide values. The suitability of this guide values concept for pesticides is demonstrated by determining the background exposure and the biomarkers of susceptibility of 250 unexposed persons as well as of more than 1200 occupationally exposed persons. As a result, a significant dependence of their health fidelity from the background exposure profile impressed on the individual polymorphism of the key enzymes was observed. Especially, the cumulative adducts of electrophilic substances and their metabolites with macromolecules like HSA and Hb turned out to be sensitive markers for the capacity of the individual metabolic rate. For alkylating and arylating pesticides the observed interindividual susceptibility to their adverse effects depends on the variability of the individual 'toxifying' and 'detoxifying' metabolic rates. Until scientific evaluation of official biological tolerance values for pesticides is carried out, it is advisable for risk prophylaxis to orientate the assessment of any individual tolerable stress and strain from pesticides to the synergism between background exposure, life style factors and biomarkers of specific susceptibility. They may be examined by a monitoring of conjugates and polymorphism marked by the individual metabolic rate. The monitoring and surveillance of pesticide exposures is mainly introduced by the recommendation of tolerable biological values from the reference value concept. This concept is an essential contribution to an objective risk discussion with regard to individual stress and strain profiles in environmental exposure scenarios.

Use of household pesticides and the risk of aplastic anaemia in Thailand. The Aplastic Anemia Study Group.

BACKGROUND: Aplastic anaemia is a severe blood dyscrasia that is more common in Thailand than in Western countries. Its a etiology remains poorly understood. METHODS: A case-control study was conducted in Bangkok and two rural regions of Thailand. The effect of household pesticides was evaluated among 253 incident cases of aplastic anaemia and 1174 hospital controls. RESULTS: A total of 54% of the cases and 61% of the controls were exposed 1-6 months previously. For most individual household pesticides and for groups classified according to chemical type (organophosphates, pyrethrins, and organochlorines), the relative risk (RR) estimates approximated 1.0; upper 95% confidence limits were below 2.0 for many comparisons. A significant association was observed for exposure to combination products containing dichlorvos and propoxur, with an overall RR estimate of 1.7 (95% confidence interval [CI]: 1.1-2.6); the estimate for regular use was 1.6 (95% CI: 0.9-2.9). CONCLUSIONS: The absence of a higher risk for the regular use of dichlorvos/propoxur reduces the credibility of the apparent association, which could well have been an artefact of multiple comparisons. We conclude that most household pesticides used in Thailand do not appear to increase the risk of aplastic anaemia.