Work with pesticides and organophosphate sheep dips

Pesticides are an important hazard in agriculture. In developed countries their use is strictly regulated. Risk assessment for new pesticides includes comparison of the potential exposures of spray operators and other farm workers with a reference value. Usually, this is derived from toxicological studies in animals with allowance for the uncertainties in extrapolating between and within species. Older pesticides undergo periodic reviews, for which epidemiological data may also be available. Unintentional fatal poisoning by pesticides is extremely rare in Britain. Documented reports of non-fatal acute poisoning are also uncommon, but there may be substantial under-ascertainment of minor incidents. Pesticides have been linked with various chronic diseases, but few associations have been clearly established. A particular concern recently in Britain has been the possibility that organophosphate insecticides can cause chronic neuropsychiatric illness.     

PON1 and neurodevelopment in children from the CHAMACOS study exposed to organophosphate pesticides in utero

Background

Paraoxonase 1 (PON1) detoxifies oxon derivatives of some organophosphate (OP) pesticides, and its genetic polymorphisms influence enzyme activity and quantity. We previously reported that maternal urinary concentrations of dialkyl phosphate (DAP) metabolites, a marker of OP pesticide exposure, were related to poorer mental development and maternally reported symptoms consistent with pervasive developmental disorder (PDD) in 2-year-olds participating in the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) study.

Objective

We determined whether PON1 genotypes and enzyme measurements were associated with child neurobehavioral development and whether PON1 modified the association of in utero exposure to OPs (as assessed by maternal DAPs) and neurobehavior.

Methods

We measured DAP concentrations in maternal urine during pregnancy, PON1₁₉₂ and PON1₋₁₀₈ genotypes in mothers and children, and arylesterase (ARYase) and paraoxonase (POase) in maternal, cord, and 2-year-olds’ blood. We assessed 353 2-year-olds on the Mental Development Index (MDI) and Psychomotor Development Index (PDI) of the Bayley Scales of Infant Development and queried their mothers on the Child Behavior Checklist to obtain a score for PDD.

Results

Children with the PON1_−108T allele had poorer MDI scores and somewhat poorer PDI scores. Children were less likely to display PDD when they or their mothers had higher ARYase activity and when their mothers had higher POase activity. The association between DAPs and MDI scores was strongest in children with PON1_−108T allele, but this and other interactions between DAPs and PON1 polymorphisms or enzymes were not significant.

Conclusion

PON1 was associated with child neurobehavioral development, but additional research is needed to confirm whether it modifies the relation with in utero OP exposure.     

Altered distribution of lipid-soluble antioxidant vitamins in juvenile sturgeon exposed to waterborne ethynylestradiol

Studies in mammals have shown that exposure to estrogenic compounds can affect lipid metabolism and plasma concentrations of lipid-soluble vitamins. However, the potential for estrogenic contaminants to induce these effects in fish has not yet been examined. The ability of the estrogen analog ethynylestradiol (EE2) to alter concentrations of the lipid-soluble vitamins A and E in plasma, liver, and kidney was investigated in juvenile lake sturgeon (430 +/- 20 g). The EE2 was delivered to the sturgeon in the tank water at nominal concentrations of 0 (control), 15, 60, or 125 ng EE2/L for a period of 25 d. Concentrations of the egg yolk precursor, vitellogenin, increased dose dependently in plasma. Plasma vitamin E (tocopherol), A1 (retinol), and A2 (dehydroretinol) were elevated by the two highest EE2 treatments compared with the controls. Esterified storage forms of vitamin A were marginally lower in the livers of fish from the highest EE2 dose group, but vitamin E levels in the liver were not significantly affected. Concentrations of vitamin E and vitamin A were significantly depleted in the kidney of fish from the two highest EE2 dose groups. Total lipid content was elevated in the gonad of fish treated with the highest dose of EE2 compared with the controls. Altered lipid and vitamin distribution may be induced by estrogen to facilitate gonadal maturation in sturgeon. Results from these studies indicate that an examination of the implications for vitamin depletion by estrogenic contaminants in juvenile fish is warranted.     

Problems in monitoring overexposure among spray workers in fruit orchards chronically exposed to diluted organophosphate pesticides

Objectives: Farmworkers applying diluted pesticides are chronically exposed to low levels of toxic substances such as organophosphates (OPs). Monitoring of serum and red cell cholinesterase (ChE) levels are often used to determine whether these workers are overexposed to OPs. There are major problems with the interpretation of ChE levels: differing definitions of `overexposed'; measurement variation and biological variation over time; and confounding factors such as alcohol misuse and certain liver conditions. The purpose of this study was to conduct a survey under field conditions to determine the extent of possible overexposure and the problems with biological monitoring using ChE levels in a spray worker population chronically exposed to OPs. Methods: A survey of 134 spray workers from 44 deciduous fruit farms in the Western Cape, South Africa, was conducted three times during the production season. Both ChE levels were determined at the end of 6 months lay-off (no spraying); during peak spraying; and at the end of the spray season. A group of 51 packshed workers with no exposure to OPs was used for comparison. Results: Despite exhaustive statistical analyses, the proportions of lowered ChE levels could not be shown to differ between the exposed and unexposed groups. The variation in ChE levels observed could be explained statistically by the high levels of alcohol misuse among the participants (76% in the exposed group, 59% in the unexposed group). Unhealthy lifestyle habits were highly prevalent amongst these workers (e.g. 83% smoked), which have long-term implications for their health and, importantly, hamper the diagnosis of overexposure. Alcohol intake was statistically associated with lowered ChE levels. Conclusions: According to different definitions of `lowered', different conclusions could be reached, which hamper reliable application in the field. The interpretation of ChE levels as an indicator of overexposure to OPs is complex, and the risk of misinterpretation in such a worker population is considerable.     

A clinical neurological,neurophysiological, and neuropsychological study of sheep farmers and dippers exposed to organophosphate pesticides

Objectives: To classify clinical diseases of the subjects with abnormal indices of peripheral neuropathy identified in field studies of sheep farmers and dippers exposed to organophosphate pesticides. To explore what neuropsychological profiles, if any, may be associated with neurophysiological damage in these subjects. Methods: A case-control study (79 subjects) nested within the cross sectional study (685 subjects) of sheep farmers from the field study. Three groups with no, possible, and probable or definite neuropathy according to field studies were recruited. Investigations comprised symptoms of neuropathy, neurologial signs, motor and sensory nerve conduction, electromyography, quantitative sensory testing, and neuropsychological tests. Results: The incidence of clinical neuropathy increased from 7% in the no neuropathy group to 52% in the probable or definite neuropathy group based on nerve conduction measurements or presence of neurological signs. Sensory abnormalities were found more often than motor deficits. Small diameter nerve fibres were also affected more than large fibres. Conclusions: The neuropathy is predominantly sensory and is characteristic of distal, chronic neuropathy with no acute features. Small fibre populations are affected more than large fibre populations. Increasing severity of neuropathy was associated with anxiety and depression as measured in the neuropsychological tests.     

Interaction of organophosphate pesticides and related compounds with the androgen receptor

Identification of several environmental chemicals capable of binding to the androgen receptor (AR) and interfering with its normal function has heightened concern about adverse effects across a broad spectrum of environmental chemicals. We previously demonstrated AR antagonist activity of the organophosphate (OP) pesticide fenitrothion. In this study, we characterized AR activity of analogues of fenitrothion to probe the structural requirements for AR activity among related chemicals. AR activity was measured using HepG2 human hepatoma cells transfected with human AR plus an androgen-responsive luciferase reporter gene, MMTV-luc. AR antagonist activity decreased as alkyl chain length of the phosphoester increased, whereas electron-donating properties of phenyl substituents of the tested compounds did not influence AR activity. Oxon derivatives of fenitrothion, which are more likely to undergo hydrolytic degradation, had no detectable AR antagonist activity. Molecular modeling results suggest that hydrogen-bond energies and the maximum achievable interatomic distance between two terminal H-bond capable sites may influence both the potential to interact with the AR and the nature of the interaction (agonist vs. antagonist) within this series of chemicals. This hypothesis is supported by the results of recent AR homology modeling and crystallographic studies relative to agonist- and antagonist-bound AR complexes. The present results are placed in the context of structure-activity knowledge derived from previous modeling studies as well as studies aimed toward designing nonsteroidal antiandrogen pharmaceuticals. Present results extend understanding of the structural requirements for AR activity to a new class of nonsteroidal, environmental, OP-related chemicals.     

Health symptoms and exposure to organophosphate pesticides in farmworkers

BACKGROUND: Few studies have examined the relationship between reported health symptoms and exposure to organophosphate (OP) pesticides. METHODS: Fisher's exact test was used to assess the relationship between self-reported health symptoms and indicators of exposure to OP pesticides in 211 farmworkers in Eastern Washington. RESULTS: The health symptoms most commonly reported included headaches (50%), burning eyes (39%), pain in muscles, joints, or bones (35%), a rash or itchy skin (25%), and blurred vision (23%). Exposure to pesticides was prevalent. The proportion of detectable samples of various pesticide residues in house and vehicle dust was weakly associated with reporting certain health symptoms, particularly burning eyes and shortness of breath. No significant associations were found between reporting health symptoms and the proportion of detectable urinary pesticide metabolites. CONCLUSIONS: Certain self-reported health symptoms in farmworkers may be associated with indicators of exposure to pesticides. Longitudinal studies with more precise health symptom data are needed to explore this relationship further.     

Effect of pesticides on cell survival in liver and brain rat tissues

Pesticides are the main environmental factor associated with the etiology of human neurodegenerative disorders such as Parkinson's disease. Our laboratory has previously demonstrated that the treatment of rats with low doses of dimethoate, zineb or glyphosate alone or in combination induces oxidative stress (OS) in liver and brain. The aim of the present work was to investigate if the pesticide-induced OS was able to affect brain and liver cell survival. The treatment of Wistar rats with the pesticides (i.p. 1/250 LD50, three times a week for 5 weeks) caused loss of mitochondrial transmembrane potential and cardiolipin content, especially in substantia nigra (SN), with a concomitant increase of fatty acid peroxidation. The activation of calpain apoptotic cascade (instead of the caspase-dependent pathway) would be responsible for the DNA fragmentation pattern observed. Thus, these results may contribute to understand the effect(s) of chronic and simultaneous exposure to pesticides on cell survival.     

苯海索在重症急性有机磷农药中毒患者救治中的应用

目的 探讨苯海索对重症有机磷农药中毒并发肌张力增高患者的影响。
方法 选择重症有机磷农药中毒并发肌张力增高患者70例, 随机分为治疗组(36例)和对照组(34例)。对照组常规给予洗胃、特殊解毒药、对症及支持治疗。治疗组患者在对照组治疗的基础上, 同时给予苯海索3次/d, 每次2 mg, 疗程3~31 d。
结果 治疗组患者呼吸衰竭发生率为19.5%, 迟发性神经病发生率为5.6%, 各低于对照组的70.6%、50.0%, 差异均有统计学意义(P < 0.01);治疗组死亡率为2.7%, 低于对照组的14.7%, 但差异无统计学意义(P>0.05)。治疗组存活患者平均住院时间为(15.9 ±3.0) d, 短于对照组存活患者的(27.3 ±3.6) d, 差异有统计学意义(P < 0.01)。
结论 苯海索对重症有机磷农药中毒并发肌张力增高患者疗效较好, 值得推广。
     

Electroencephalogram, cognitive state, psychological disorders, clinical symptom, and oxidative stress in horticulture farmers exposed to organophosphate pesticides

The aim of this paper was to study the toxicity of organophosphate (OP) pesticides in exposed farmers for electroencephalography, cognitive state, psychological disorders, clinical symptom, oxidative stress, acetylcholinesterase, and DNA damage. A comparative cross-sectional analysis was carried out in 40 horticulture farmers who were exposed to OPs in comparison to a control group containing 40 healthy subjects with the same age and sex and education level. Lipid peroxidation (LPO), superoxide dismutase (SOD), catalase, glutathione peroxidase, DNA damage, total antioxidant capacity (TAC), total thiol molecules, and acetylcholinesterase (AChE) activity were measured in the blood of subjects. Clinical examination and complete blood test were undertaken in order to record any abnormal sign or symptoms. Cognitive function, psychological symptoms, and psychological distress were examined and recorded. Comparing with controls, the farmers showed higher blood levels of SOD and LPO while their TAC decreased. Farmers showed clinical symptoms such as eczema, breathing muscle weakness, nausea, and saliva secretion. Regarding cognitive function, the orientation, registration, attention and calculation, recall, and language were not significantly different in farmers and controls. Among examinations for psychological distress, only labeled somatization was significantly higher in farmers. The present findings indicate that oxidative stress and inhibition of AChE can be seen in chronically OP-exposed people but incidence of neuropsychological disorders seems a complex multivariate phenomenon that might be seen in long-term high-dose exposure situations. Use of supplementary antioxidants would be useful in the treatment of farmers.     

Prenatal exposure to organophosphate pesticides and IQ in 7-year-old children

Context: Organophosphate (OP) pesticides are neurotoxic at high doses. Few studies have examined whether chronic exposure at lower levels could adversely affect children’s cognitive development.Objective: We examined associations between prenatal and postnatal exposure to OP pesticides and cognitive abilities in school-age children.Methods: We conducted a birth cohort study (Center for the Health Assessment of Mothers and Children of Salinas study) among predominantly Latino farmworker families from an agricultural community in California. We assessed exposure to OP pesticides by measuring dialkyl phosphate (DAP) metabolites in urine collected during pregnancy and from children at 6 months and 1, 2, 3.5, and 5 years of age. We administered the Wechsler Intelligence Scale for Children, 4th edition, to 329 children 7 years of age. Analyses were adjusted for maternal education and intelligence, Home Observation for Measurement of the Environment score, and language of cognitive assessment.Results: Urinary DAP concentrations measured during the first and second half of pregnancy had similar relations to cognitive scores, so we used the average of concentrations measured during pregnancy in further analyses. Averaged maternal DAP concentrations were associated with poorer scores for Working Memory, Processing Speed, Verbal Comprehension, Perceptual Reasoning, and Full-Scale intelligence quotient (IQ). Children in the highest quintile of maternal DAP concentrations had an average deficit of 7.0 IQ points compared with those in the lowest quintile. However, children’s urinary DAP concentrations were not consistently associated with cognitive scores.Conclusions: Prenatal but not postnatal urinary DAP concentrations were associated with poorer intellectual development in 7-year-old children. Maternal urinary DAP concentrations in the present study were higher but nonetheless within the range of levels measured in the general U.S. population.     

Pesticide loadings of select organophosphate and pyrethroid pesticides in urban public housing

We investigated the magnitude and distribution of pyrethroid and organophosphate pesticide loadings within public housing dwellings in Boston, Massachusetts and compared the results using various sampling methods. We collected dust matrices from living room and kitchen in 42 apartments and analyzed for eleven pyrethoids (e.g., permethrin and cyfluthrin) and two organophosphates (chlorpyrifos and diazinon) in house dust using GC/MS. Agreement between sampling methods were evaluated using Spearman correlations and Kappa statistics. Permethrin and chlorpyrifos were detected in kitchen floor wipes in all homes, followed in frequency of detects by diazinon (98%), cypermethrin (90%) and cyfluthrin (71%). At least six pesticides were detected in kitchen floor wipes in the majority of the homes (range 3-8). Positive and statistically significant correlations among dust matrices were observed between kitchen floor wipes and living room vacuum dust, including for diazinon (r=0.62) and cyfluthrin (r=0.69). Detection of several pesticides including banned or restricted use products in some public housing units, underscore the need for alternative pest management strategies that embrace the safe and judicious use of pest control products.     

Distribution of organophosphate pesticides in two artificial plasmas: FSB-FSP]

Here is an attempt to establish that a close relation exists between the chemical formulae of organophosphates and their affinities for lipids, proteins and water. We carried out this study on two systems similar to human plasma. First, each component was sorted, then the organophosphates were detected and titrated by gas chromatography with flame photometry detector. Thiophosphates had a greater affinity for lipids than phosphates. Fixation of proteins was only observed on three hydrophilous organophosphates: phosphamidon, dichlorvos, ciodrin.     

Elevated quantitative vibrotactile threshold among workers previously poisoned with methamidophos and other organophosphate pesticides

To evaluate chronic effects of acute organophosphate pesticide poisoning, quantitatively determined vibrotactile thresholds were measured as an index of peripheral neuropathy among agricultural workers in Nicaragua. Thirty-six male workers were evaluated between 10 and 34 months after hospitalization for acute organophosphate poisoning and compared to an age- and sex-matched community reference group. Vibrotactile thresholds were measured quantitatively in right and left index fingers and right and left great toes. Study subjects were stratified into three groups: 1) never poisoned; 2) poisoned with organophosphates other than methamidophos, agents which have not been reported to cause peripheral neuropathy; and 3) poisoned with methamidophos, a peripheral neurotoxin. For all digits, there was a statistically significant trend of increasing age-and height-adjusted thresholds across these three exposure categories. Over one fourth of patients previously poisoned with methamidophos we studied had abnormal vibrotactile thresholds. These results suggest that previously reported cases of organophosphate-induced delayed polyneuropathy may represent only the worst disease in a spectrum of impairment, a sequela of exposure that may be much more common than previously thought. © 1994 Wiley-Liss, Inc.     

Long-term neurobehavioral effects of mild poisonings with organophosphate and n-methyl carbamate pesticides among banana workers

Organophosphate poisoning has been associated with chronic neurobehavioral dysfunction, but no epidemiologic data exist with regard to long-term consequences from carbamate poisoning. This cross-sectional study evaluated the neurobehavioral performances of 81 banana workers who, on average 27 months earlier, had received medical attention not requiring hospitalization for mild occupational poisoning by either an organophosphate or a carbamate pesticide. These performances were compared with those of 130 banana workers who had never sought medical attention for pesticide poisoning. Poisoned subjects did less well than controls on tests measuring psychomotor and visuomotor skills, language function, and affect, the differences being significant for coding skills on the Digit-Symbol test and two tests of neuropsychiatric symptoms. These deficits, in particular a marked increase of neuropsychiatric symptoms, occurred among the organophosphate-poisoned subjects, but small deficits in performance were also seen in the carbamate-poisoned subjects. The performances of the previously poisoned subjects who had had contact with cholinesterase inhibitors within three months before testing were particularly poor. These findings in workers with mild poisoning are consistent with previous findings of persistent damage to the central nervous system from organophosphate poisoning. The possibility of persistent neurobehavioral effects associated with poisonings by nmethyl carbamate insecticides cannot be excluded. Workers with histories of poisoning may be more susceptible to neurobehavioral effects with subsequent exposures.