Assessment of thyroid function in pesticide formulators

Thirty male pesticide formulators exposed to the dust and liquid formulation of endosulfan, quinalphos, chlorpyriphos, monocrotophos, lindane, parathion, phorate, and fenvalerate and 20 comparable control subjects from the same area of study were examined for the evaluation of thyroid function tests. The level of TSH was elevated (about 28%) in pesticide formulators as compared to a control group, but the increase was statistically insignificant. Based on the individual TSH measurement, 3 of 30 formulators had isolated elevated levels of TSH and seem to have acquired sub-clinical hypothyroidism; five had TSH values slightly elevated to the upper boarder line (4.03 muIU/ml); and the majority of formulators (N= 22) had TSH values in the normal range varying from 1.29 to 3.9 muIU/ml. Total T3 was suppressed significantly (P< 0.01) in formulators, while marginal decrease (about 7%) was noticed in T4 level. This study indicated thyroid function impairment in few pesticide formulators.     

Biological monitoring and health surveillance of a group of greenhouse pesticide sprayers

Repeated extensive medical examinations were carried out in 11 workers spraying organophosphate (OP), carbamate and pyrethroid pesticides in greenhouses during the whole year and in 10 control persons. On a questionnaire their social, health and family status and their working conditions were recorded. Before and after a regular spraying period with pyrethroids for 3 months the following tests were carried out: urinalysis, haematology, immunoglobulin (Ig) G, IgA and IgM levels, whole blood cholinesterase (ChE) activity, serum gamma-glutamyltransferase (GGT) activity, chromosome analysis and electrocardiography (ECG). Atmospheric concentrations of pyrethroids as well as their concentration in the blood and urine of pesticide workers were determined by means of gas-liquid chromatography (GLC). No abnormalities related to the work were found in the tests.     

Immune parameters in biological monitoring of pesticide exposure: current knowledge and perspectives.

Exposure to pesticides can cause a number of effects on the immune system, varying from a slight modulation of immune functions to the development of clinical immune diseases. The aim of this study has been reviewing published data on immune effects of pesticides in humans, with particular attention for effects observed in absence of any other change, and to the possibility of identifying a dose effect relationship. Some evidence of immunotoxic effects in man involve organophosphorus compounds, some organochlorine insecticides (OC), some carbamates, some phenoxy herbicides, dithiocarbamates, and pentachlorophenol (PCP). The alterations are usually observed in absence of any other change; in some cases, data suggest the presence of a dose effect relationship. The prognostic significance of the observed changes is still unclear. The Authors propose a tier approach to assess immune effects in humans.     

Integration of biological monitoring, environmental monitoring and computational modelling into the interpretation of pesticide exposure data: introduction to a proposed approach

Open field, variability of climatic and working conditions, and the use of complex mixtures of pesticides makes biological and environmental monitoring in agriculture, and therefore risk assessment and management, very complicated. A need of pointing out alternative risk assessment approaches, not necessarily based on measures, but simple, user-friendly and reliable, feasible also in the less advanced situations and in particular in small size enterprises, arises. This aim can be reached through a combination of environmental monitoring, biological monitoring and computational modelling. We have used this combination of methods for the creation of "exposure and risk profiles" to be applied in specific exposure scenarios, and we have tested this approach on a sample of Italian rice and maize herbicide applicators. We have given specific "toxicity scores" to the different products used and we have identified, for each of the major working phases, that is mixing and loading, spraying, maintenance and cleaning of equipment, the main variables affecting exposure and inserted them into a simple algorithm, able to produce "exposure indices". Based on the combination of toxicity indices and exposure indices it is possible to obtain semiquantitative estimates of the risk levels experienced by the workers in the exposure scenarios considered. Results of operator exposure data collected under real-life conditions can be used to validate and refine the algorithms; moreover, the AOEL derived from pre-marketing studies can be combined to estimate tentative biological exposure limits for pesticides, useful to perform individual risk assessment based on technical surveys and on simple biological monitoring. A proof of principle example of this approach is the subject of this article.     

Evaluation of oxidative stress and genotoxicity in organophosphorus insecticide formulators

The aim of this study was to evaluate genotoxicity and oxidative stress in workers who formulate organophosphorus (OP) pesticides. In this survey, blood leukocytes and erythrocytes of a group of 21 pesticide formulating workers and an equal number of control subjects were examined for genotoxicity and oxidative stress parameters. The mean comet tail length and mean comet length were used to measure DNA damage. Lipid peroxidation level, catalase, superoxide dismutase (SOD) and glutathione peroxidase activities in erythrocytes were analysed as biomarkers of oxidative stress. In addition, the acetylcholinesterase activity was measured as a biomarker of toxicity. The average duration of employment of workers in the factory was 97 months. Results indicated that chronic exposure (multiple-dose, greater than or equal to 6 months duration) to OP pesticides was associated with increased activities of catalase, SOD and glutathione peroxidase in erythrocytes. The level of lipid peroxidation and acetylcholinesterase activity did not show any significant differences between the two groups. The results also indicated that chronic exposure to OP pesticides was associated with increased DNA damage. It is concluded that human chronic exposure to OP pesticides may result in stimulated antioxidant enzymes and increased DNA damage in the absence of depressed acetylcholinesterase levels. Routine genotoxicity monitoring concomitant to acetylcholinesterase activity in workers occupationally exposed to OP insecticides is suggested.     

Toxicological considerations for protein components of biological pesticide products.

The toxicity of protein components of microbial pesticide products is evaluated at EPA by requiring that pesticide manufacturers conduct a thorough taxonomic evaluation of the active microbial ingredient. The requirement for acute toxicity testing by dosing laboratory animals with the active microbial ingredient and with fermentation growth medium materials provides additional information on the toxicity of protein components of microbial pesticides. The potential for toxicity from proteins associated with contaminating organisms is addressed by use of appropriate quality control procedures to minimize or prevent growth of contaminants and by screening of fermentation batches for known human/mammalian pathogens. These considerations also would apply to any biochemical pesticide that is formed via the growth of a microorganism. If a protein itself is intended for commercial use as an active pesticide ingredient, acute exposure studies and in vitro digestibility studies could be done to answer potential concerns regarding toxicity.     

Health impact and economic burden of alcohol consumption in India

BackgroundThe health and economic consequences of alcohol consumption have been assessed mainly in developed countries. This study aims to estimate health impact and economic burden attributable to alcohol use in India.MethodsA combination of decision tree and mathematical markov model was parameterized to assess the health effects and economic cost attributable to alcohol consumption. Health effect of alcohol was modelled for a time period of 2011 to 2050 on three sets of conditions – liver disease, cancers and road traffic accidents. Estimates of illness, death, life years lost and quality adjusted life years (QALYs) gained were estimated as a result of alcohol consumption. Both direct and indirect costs were estimated to determine economic burden. Future costs and consequences were discounted at 3% for time preferences of cost and utility. Uncertainties in parameters were assessed using probabilistic sensitivity analysis.ResultsBetween 2011 and 2050, alcohol attributable deaths would lead to a loss of 258 million life years. In contrast, 552 million QALYs would be gained by eliminating alcohol consumption. Treatment of these conditions will impose an economic burden of INR 3127 billion (US$ 48.11 billion) on the health system. Societal burden of alcohol, inclusive of health system cost, out of pocket expenditure and productivity losses will be INR 121,364 billion (US$ 1867 billion). Even after adjusting for tax receipts from sale of alcohol, alcohol poses a net economic loss of INR 97,895 billion (US$ 1506 billion). This amounts to an average loss of 1.45% of the gross domestic product (GDP) per year to the Indian economy.ConclusionAlcohol causes significant negative health impact and economic burden on Indian society and evidence informed policy interventions are needed to control alcohol attributable harm.     

Neurologic symptoms in licensed pesticide applicators in the Agricultural Health Study

Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate pesticide levels. We analysed cross-sectional data from 18 782 Caucasian, male, licensed pesticide applicators, enrolled in the Agricultural Health Study from 1993 to 1997. Applicators provided information on lifetime pesticide use, and 23 neurologic symptoms typically associated with pesticide intoxication. Increased risk of experiencing >/=10 symptoms during the year before enrollment was associated with cumulative pesticide use, personally mixing or applying pesticides, pesticide-related medical care, diagnosed pesticide poisoning, and events involving high personal pesticide exposure. Greatest risk was associated with use of organophosphate and organochlorine insecticides. Results were similar after stratification by pesticide use during the year before enrollment, or exclusion of applicators with a history of pesticide poisoning, or high-exposure events. Use of pesticide application methods likely to involve high personal exposure was associated with greater risk. Groups of symptoms reflecting several neurologic domains, including affect, cognition, autonomic and motor function, and vision, were also associated with pesticide exposure. These results suggest that neurologic symptoms are associated with cumulative exposure to moderate levels of organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.     

Organochlorine and organophosphorus pesticide residues in breast milk from Bhopal,Madhya Pradesh,India

HCH isomers, endosulfan, malathion, chlorpyrifos, and methyl-parathion were monitored in human milk samples from Bhopal, Madhya Pradesh. The endosulfan concentrations were highest and exceeded the sigma-HCH, chlorpyrifos, and malathion concentrations by 3.5-, 1.5-, and 8.4-fold, respectively. Through breast milk, infants consumed 8.6 times more endosulfan and 4.1 times more malathion than the average daily intake levels recommended by the World Health Organization. A correlation analysis (r values) between mothers' age and the content of the chemicals accumulated in breast milk indicated a substantial degree of correlation for malathion (r = 0.5). The other chemicals showed low to negligible correlation with donor age.     

Therapeutic drug monitoring of atazanavir: surveillance of pharmacotherapy in the clinic

BACKGROUND: Therapeutic failure with antiretroviral therapy (ART) is a substantial issue where viral rebound, viral resistance and drug-related toxicity remain serious concerns. Drug exposure-response relationships have been described for the protease inhibitors, pharmacokinetic variability is substantial for this class of drugs and drug interactions can also alter ART exposure. Given this background we established a therapeutic drug monitoring (TDM) service to monitor atazanavir (ATV) plasma concentrations early after the therapy was made available to treatment-experienced people infected with HIV who were managed in a clinical setting. METHODS: This was a prospective observational study which evaluated plasma samples from 110 highly treatment-experienced people with HIV using TDM and applied pharmacokinetic analysis over a five month period. RESULTS: ATV trough concentrations exhibited substantial intersubject variability (<25-2108 microg l(-1)). A substantial number of subjects (50%,13/26) who received ATV400 mg daily had low exposure to ATV. Serum bilirubin concentrations correlated significantly with higher ATV trough concentrations (rho = 0.803; P < 0.001) and 55% (29/53) of subjects who received ATV300/100 mg RTV daily had plasma concentrations above a proposed target concentration associated with elevated bilirubin concentrations. This study confirmed low ATV exposure in eight subjects with HIV receiving ATV 400 mg daily. Reasons for low ATV exposure in this cohort include administration of interacting drugs, including a possible interaction with ritonavir, fluticasone and ATV, impaired ATV absorption secondary to suspected achlorhydria and potential interactions with colchicine and nandrolone. Viral load remained undetectable in most of these subjects with low ATV exposure. CONCLUSIONS: TDM and targeted pharmacokinetic studies should be viewed as fundamental tools in the development and clinical application of ART, to improve pharmacotherapy for people with HIV.     

Neurobehavioral function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study

Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning, little is known about the cognitive effects of chronic OP exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and neurobehavioral (NB) function, NB tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61 years (SD=12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning; and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, we found no consistent evidence of an association between OP pesticide use and adverse NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null results include a true absence of effect as well as possible selective participation by healthier applicators.     

Sperm motility in the fishes of pesticide exposed and from polluted rivers of Gomti and Ganga of north India

Investigation of lethal dose of γ-HCH (gamma isomer of hexachlorocyclohexane), DDT (dichlorodiphenyltrichloroethane) and chlorpyrifos on spermatozoa motility after 40 days exposure in catfish, Heteropneustes fossilis was done under laboratory conditions. The sperm motility was done in the fishes captured from unpolluted ponds of Gujartal considering as reference site and polluted rivers Gomti and Ganga of north India at pre-spermiating stage. Results indicate that 1 ppm of γ-HCH, DDT and chlorpyrifos was lethal dose on sperm motility. The motility of spermatozoa decreased in insecticide exposed fish as well as in the fishes of polluted rivers when compared with their respective controls. The sperm motility was highest at 1:2000 (testicular milt: extender) dilution and duration of sperm motility was 90 s after post-activation. The duration of motility also declined in the fishes captured from polluted rivers when compared with the same species captured from the reference site. It is concluded that the insecticides decrease the sperm motility and its duration in exposed fish as well as in the captured fishes from polluted rivers causing the decline in fish population of riverine systems due to influence of xenobiotics on the endocrine system.     

Environmental and biological monitoring in the estimation of absorbed doses of pesticides

Exposure to pesticides affects most of the population, not only persons occupationally exposed. In a context of high variability of exposure, biological monitoring is important because of the various routes by which exposure can occur and because it assesses both occupational and non-occupational exposure. The main aim of this paper was to critically compare estimates of absorbed dose measured by environmental and biological monitoring in situations in which they could both be applied. The combination of exposure measurements and biological monitoring was found to provide extremely important information on the behaviour of employees, and on the proper use and effectiveness of personal protection equipment.     

Construction of a database of benzene biological monitoring

Biological monitoring of occupational exposure to benzene has been conducted in the petroleum, steel and chemical industries. The urinary benzene-specific biomarker, S-phenylmercapturic acid (PMA), was quantified in post-shift samples using a sensitive enzyme-linked immunosorbent assay (ELISA) and expressed as a function of urinary creatinine concentration. The assay, based on a PMA-specific antiserum, is sufficiently sensitive to measure PMA levels in non-occupationally exposed control subjects. The assay delivers batch results in a timely manner which may be as short as 3 h. Samples were analysed from groups of workers engaged in coke oven combustion processes, petroleum refining and decontamination of a benzene land spill. The construction of a database of results provides an index of benzene uptake as a consequence of the respective work processes and tasks and readily enables benchmarking exercises aimed at comparing degrees of exposure across segments of industry.