Use of cotinine biomarker in workers to detect green tobacco sickness. / Uso de biomarcador cotinina em trabalhadores para detecção da doença da folha verde do tabaco.

OBJECTIVE: using the urinary cotinine biomarker to verify the occurrence of green tobacco sickness in workers who cultivate Burley tobacco. METHOD: paired case-control study, based on smoking status and on the 1:4 ratio, with participation of 20 case workers and 91 controls. Data collection included household surveys and urine collection for cotinine examination. Student's T-Test, the Mann-Whitney test, Pearson's chi-square or Fisher's exact tests were used. RESULTS: of the 23 suspected cases, 20 showed elevated levels of cotinine, signs and symptoms of headache, skin irritation, nausea, sickness and general malaise, especially in the morning. Most had worked with tobacco that was wet from the morning dew and when the weather was warm. CONCLUSION: there are signs suggestive of green tobacco sickness in Burley tobacco workers. The action of health professionals is necessary for the development of health promotion and preventive actions addressing work-related illness.

Urinary cotinine in tobacco farmers in Southern Brazil.

OBJECTIVE: To describe urinary cotinine levels in tobacco farmers. METHODS: A cross-sectional study was conducted in 2,570 tobacco farmers. All participants that reported green tobacco sickness in the week prior to the interview plus a subsample of 492 pesticide applicators were included. We collected urinary samples and information about sociodemographic, behavioral, dietary, occupational characteristics, and pesticide poisoning during their lifetime. Stratification by sex and smoking was performed and the Wilcoxon and Kruskal-Wallis non-parametrical tests were used to analyze cotinine means. RESULTS: This study included 582 individuals. There was no difference in urinary cotinine means between green tobacco sickness symptomatic and asymptomatic individuals. Among non-smokers, having picked tobacco in the previous week was associated with higher cotinine means in both genders. Cotinine levels were higher on the first day of symptoms and reduced exponentially with each day in female non-smokers. Male non-smokers had higher levels on the second day and a more gradual reduction. The cotinine level rose up to 15 cigarettes/day of consumption. CONCLUSIONS: The urinary cotinine measures exposure to nicotine up to its saturation point; while green tobacco sickness, affected by tolerance, indicates nicotine poisoning. Strategies to reduce nicotine exposure in tobacco production are needed. Mechanization could be an alternative, as long as it overcame the challenge of irregular terrain and did not affect the quality of the leaf. More studies are needed to evaluate the chronic effect of nicotine exposure.

Urinary cotinine in tobacco farmers in Southern Brazil

ABSTRACT OBJECTIVE To describe urinary cotinine levels in tobacco farmers. METHODS A cross-sectional study was conducted in 2,570 tobacco farmers. All participants that reported green tobacco sickness in the week prior to the interview plus a subsample of 492 pesticide applicators were included. We collected urinary samples and information about sociodemographic, behavioral, dietary, occupational characteristics, and pesticide poisoning during their lifetime. Stratification by sex and smoking was performed and the Wilcoxon and Kruskal-Wallis non-parametrical tests were used to analyze cotinine means. RESULTS This study included 582 individuals. There was no difference in urinary cotinine means between green tobacco sickness symptomatic and asymptomatic individuals. Among non-smokers, having picked tobacco in the previous week was associated with higher cotinine means in both genders. Cotinine levels were higher on the first day of symptoms and reduced exponentially with each day in female non-smokers. Male non-smokers had higher levels on the second day and a more gradual reduction. The cotinine level rose up to 15 cigarettes/day of consumption. CONCLUSIONS The urinary cotinine measures exposure to nicotine up to its saturation point; while green tobacco sickness, affected by tolerance, indicates nicotine poisoning. Strategies to reduce nicotine exposure in tobacco production are needed. Mechanization could be an alternative, as long as it overcame the challenge of irregular terrain and did not affect the quality of the leaf. More studies are needed to evaluate the chronic effect of nicotine exposure.

Simultaneous exposure to multiple heavy metals and glyphosate may contribute to Sri Lankan agricultural nephropathy.

BACKGROUND: Sri Lankan Agricultural Nephropathy (SAN), a new form of chronic kidney disease among paddy farmers was first reported in 1994. It has now become the most debilitating public health issue in the dry zone of Sri Lanka. Previous studies showed SAN is a tubulo-interstitial type nephropathy and exposure to arsenic and cadmium may play a role in pathogenesis of the disease. METHODS: Urine samples of patients with SAN (N = 10) from Padavi-Sripura, a disease endemic area, and from two sets of controls, one from healthy participants (N = 10) from the same endemic area and the other from a non-endemic area (N = 10; Colombo district) were analyzed for 19 heavy metals and for the presence of the pesticide- glyphosate. RESULTS: In both cases and the controls who live in the endemic region, median concentrations of urinary Sb, As, Cd, Co, Pb, Mn, Ni, Ti and V exceed the reference range. With the exception of Mo in patients and Al, Cu, Mo, Se, Ti and Zn in endemic controls, creatinine adjusted values of urinary heavy metals and glyphosate were significantly higher when compared to non-endemic controls. Creatinine unadjusted values were significant higher for 14 of the 20 chemicals studied in endemic controls and 7 in patients, compared to non-endemic controls. The highest urinary glyphosate concentration was recorded in SAN patients (range 61.0-195.1 µg/g creatinine). CONCLUSIONS: People in disease endemic area exposed to multiple heavy metals and glyphosate. Results are supportive of toxicological origin of SAN that is confined to specific geographical areas. Although we could not localize a single nephrotoxin as the culprit for SAN, multiple heavy metals and glyphosates may play a role in the pathogenesis. Heavy metals excessively present in the urine samples of patients with SAN are capable of causing damage to kidneys. Synergistic effects of multiple heavy metals and agrochemicals may be nephrotoxic.

Oregon indigenous farmworkers: results of promotor intervention on pesticide knowledge and organophosphate metabolite levels.

OBJECTIVES: To examine changes in health beliefs, pesticide safety knowledge, and biomarkers of pesticide exposure in indigenous farmworkers who received enhanced pesticide safety training compared with those receiving the standard training. METHODS: Farmworkers in Oregon were randomly assigned to either a promotors pesticide safety training program or a standard video-based training. Spot urine samples were analyzed for dialkyl phosphate urinary metabolites. Pre-/postintervention questionnaires were used to measure pesticide safety knowledge, health beliefs, and work practices. RESULTS: Baseline to follow-up improvements in total pesticide knowledge scores were higher in the promotor group than in the standard video group. Pairwise differences in mean concentrations of dialkyl phosphate metabolite levels showed declines from baseline to follow-up for both intervention groups. CONCLUSIONS: Results showed reductions in pesticide exposure in indigenous-language speaking farmworkers who received enhanced pesticide safety training.

Epidemiologic investigation of an occupational illness of tobacco harvesters in southern Brazil, a worldwide leader in tobacco production.

OBJECTIVES: As part of smoking surveillance, the authors conducted an epidemiologic investigation in southern Brazil to identify the occurrence of Green Tobacco Sickness and risk factors for illness and to recommend control and prevention measures. METHODS: A 1:2 case-control study matched by subjects' smoking habits. The study population was residents of Candelária, Rio Grande do Sul state, who farm tobacco and provided a urine sample for cotinine measurement by high-performance liquid chromatography. Confirmed cases were persons with compatible clinical presentation (headache, nausea, vomit, dizziness or weakness) and cotinine level >10 ng/ml. Controls were persons without compatible signs or symptoms. The association measure was the matched OR with 95% CIs and p<0.05. RESULTS: Of 33 confirmed cases, 64% were men, average age was 33 years (SD ± 11.8 years) and 57% were landowners. Cases have had similar illness in the past and were likelier to be workers hired by farmers-landowners than controls. Multivariate analysis yielded independent association between these variables and illness, controlled for age and sex. Contact with pesticides and working with wet tobacco leaves were not associated with illness. CONCLUSIONS: The authors confirmed Green Tobacco Sickness in southern Brazil; the authors recommend investigation of its prevalence in tobacco-growing regions and monitoring of and education about the disease and its prevention by occupational health authorities.

[Occupational exposure to pesticides among farmers of the Lódz' voivodeship agricultural area]. / Zawodowa ekspozycja na wybrane pestycydy rolników z terenów rolniczych województwa Lódzkiego.

BACKGROUND: Pesticides are widely used in agriculture for the crop protection. Despite advanced mechanization of the agricultural production, the population's exposure to these chemicals is still significant. The objective of the study was to evaluate farmers' occupational exposure to two most frequently used pesticides: MCPA and 2,4-D. MATERIAL AND METHODS: Pesticide exposure was assessed in 24 farmers, living in the Lódz voivodeship agriculture area, for 71 sprayings performed on their arable areas. The exposure assessment methods were used to estimate workers' exposure to selected pesticides (MCPA and 2,4-D). The analysis covered the biological material (urine) collected on the day of pesticides spraying: in the morning before spraying (Sample A), in the evening after spraying (Sample B) and on the next day (Sample C). RESULTS: The level of pesticides found in farmers' urine was growing from sample A to sample C. The highest level of pesticides was found in sample C and the lowest in sample A. The predictors of the pesticide level were: sample collection time (urine concentration of pesticides in sample C compared with sample B) (p = 0.002), concentration of pesticides in sample A (p = 0.012) and the amount of products used during spraying (p = 0.021). 'The use of protective equipment was at the border of statistical significance (p = 0.059). The differences in exposure between farmers can be only partly explained by the analyzed exposure predictors. CONCLUSIONS: The study not only confirmed the presence of occupational exposure but also showed the level of exposure among farmers under study. This is very important because in Poland the level of exposure among farmers is unknown and studies using the biological monitoring are very rare.

Urinary dialkyl phosphate levels before and after first season chlorpyrifos spraying amongst farm workers in the Western Cape, South Africa.

The study investigated urinary levels of dialkyl phosphates resulting from pesticide exposure amongst 40 farm workers. Workers were tested (urinary dialkyl phosphate levels, anthropometry, short exposure questionnaire) before and after the first day of seasonal chlorpyrifos spraying. Median baseline urinary dialkyl phosphates was high amongst both non-applicators (1587.5 µg/g creatinine, n = 8) and applicators (365.6 µg/g creatinine, n = 9). There was not much evidence of an increase in post-spray dialkyl phosphates levels from pre-spray levels amongst both applicators and non-applicators. Hours mixing, spraying, driving a tractor and hours worked by non-applicators were not significantly associated with an increase in post-spray dialkyl phosphate levels, adjusting for age, height, weight, gender, use of empty pesticide containers and self-reported kidney problems. Past applicator status was weakly positively associated with pre-spray dialkyl phosphate levels adjusting for age, height, weight, and gender, self-reported kidney problems, smoking and alcohol (ß= 1019.5, p = 0.307, R² = 0.28). The high dialkyl phosphate levels call for an epidemiological investigation into the health effects of organophosphorous pesticides.

Chlorpyrifos exposures in Egyptian cotton field workers.

Neurobehavioral deficits have been reported in Egyptian pesticide application teams using organophosphorus (OP) pesticides, but whether these effects are related to OP pesticide exposures has yet to be established. In preparation for a comprehensive study of the relationship between OP pesticide dose and neurobehavioral deficits, we assessed exposure within this population. We conducted occupational surveys and workplace observations, and collected air, dermal patch and biological samples from applicators, technicians and engineers involved in chlorpyrifos applications during cotton production to test the hypotheses that: (1) dermal exposure was an important contributor to internal dose and varied across body regions; and (2) substantial differences would be seen across the three job categories. Applicators were substantially younger and had shorter exposure histories than did technicians and engineers. Applicators and technicians were observed to have relatively high levels of skin or clothing contact with pesticide-treated foliage as they walked through the fields. Both dermal patch loadings of chlorpyrifos and measurements of a chlorpyrifos-specific metabolite (TCPy) in urine confirmed substantial exposure to and skin absorption of chlorpyrifos that varied according to job category; and dermal patch loading was significantly higher on the thighs than on the forearms. These findings support our hypotheses and support the need for research to examine neurobehavioral performance and exposures in this population. More importantly, the exposures reported here are sufficiently high to recommend urgent changes in work practices amongst these workers.

DNA damage in horticultural farmers: a pilot study showing an association with organophosphate pesticide exposure.

A study of horticultural farmers exposed to organophosphate pesticides (OPs) and controls investigated the relationships between OP exposure, DNA damage and oxidative stress. Blood acetylcholinesterase (AChE) and urinary dialkylphosphate (DAP) levels determined exposure and 8-hydroxy-29- deoxyguanosine (8OHdG) indicated oxidative stress status. The farmers had approximately 30% lower AChE activity and increased DAP levels compared with the controls, reflecting moderate OP exposure. They had higher DNA damage than the controls and there was a significant positive relationship between DAP and DNA damage with greater than 95% power. The farmers also had a significant positive relationship between urinary DAP and 8OHdG levels.

Organophosphorus pesticide exposure decreases sperm quality: association between sperm parameters and urinary pesticide levels.

Several studies have suggested that human semen quality has declined over the past decades and some of them have associated it with occupational exposure to pesticides. However, most of these studies have not been associated with a reliable exposure level and have been designed mostly as cross-sectional studies. The present work evaluates, in a longitudinal follow-up study, the effect of organophosphate pesticides (OP) at three occupational exposure levels on semen quality. In addition, the study examined the association between OP urinary levels and sperm parameters in exposed and unexposed workers. A total of 139 semen samples from 52 volunteers were assessed. Urinary OP levels were measured by gas-liquid chromatography. The results revealed that the poorest semen quality was found among the subjects with the highest OP exposure and the highest urinary OP levels. Seasonal variations in sperm concentration and sperm count were registered. The results showed a significant decrease in total sperm count among subjects with the highest exposure to OP. Further studies assessing the effects of OP on male reproductive health should be controlled by the variability in human sperm parameters, sperm seasonality, spermatogenesis time and the changing OP exposure level in men highly exposed to OP.

Changes in serum markers indicative of health effects in vineyard workers following exposure to the fungicide mancozeb: an Italian study.

The aim of this study was to investigate the health effects induced by exposure to the fungicide mancozeb in Italian vineyard workers. Ninety-three Italian subjects entered the study - 48 vine-growers intermittently exposed to mancozeb and 45 healthy controls. The subjects were investigated three times: before the seasonal application of pesticides (T0), 30 days after the beginning of the application period (T30), and 45 days after T0 (T45). At T0 the comparison between agricultural workers and controls showed a higher prevalence of cold or flu symptoms, a statistically significant lower percentage of monocytes, higher absolute count of T lymphocytes, CD4 and natural killer cells, and lower plasma levels of IgA and IgM in workers. Such differences were not confirmed at T30 and T45. In fact at T30 in exposed workers, besides a significant increase of urinary ethylenethiourea, confirming mancozeb exposure, T lymphocytes, CD4 and natural killer cells, IgA and IgM returned to values comparable to those observed in controls. Moreover, no other differences in clinical signs, haematological, and immune parameters, such as the immune functional capability evaluated as a response to hepatitis B vaccination, was observed. Altogether the differences between exposed and controls were not consistently correlated to any clinical impairment and suggest that the seasonal application of mancozeb does not pose a significant health risk to exposed subjects.

Gas chromatographic-tandem mass spectrometric method for the quantitation of carbofuran, carbaryl and their main metabolites in applicators' urine.

A new gas chromatographic-tandem mass spectrometric method has been developed and validated for the determination of two N-methylcarbamates, carbofuran and carbaryl and their metabolites in applicators' urine specimens. Mild conditions were used for sample preparation based on enzymic hydrolysis and solid-phase extraction using Oasis HLB sorbent cartridges. Amides, phenols and ketones were first converted to volatile derivatives of trifluoroacetic acid anhydride (TFAA) and afterwards were quantitated using tandem mass spectrometry. Linear calibration equations (1-200 ng mL(-1) urine) were obtained from fortified urine samples for all eight compounds, carbaryl, 1-naphthol, 2-naphthol, and carbofuran, 3-hydroxycarbofuran, 7-phenol, carbofuran-3-keto, 3- hydroxycarbofuranphenol. For all compounds, the limit of detection was lower than 0.1 ng mL(-1). Precision for all compounds, at the concentrations of 1, 10 and 100 ng mL(-1) (n = 5) in-fortified urine samples ranged from 0.7% to 18%. Accuracy was calculated at two concentrations 8 and 80 ng mL(-1) (n = 5) and ranged from -8.4% to 8.2%. Relative recoveries at concentrations of 1, 10 and 100 ng mL(-1), ranged from 71% to 116%. The method was successfully applied to five male applicators and 10 non-applicators (including both smokers and non-smokers).

Farmworker exposure to organophosphorus pesticide residues during apple thinning in central Washington State.

The purpose of this study was to characterize worker exposure to azinphos-methyl (Guthion) over an entire 4-6 week apple-thinning season. Twenty workers from three work sites in the Chelan-Douglas County region of Washington state were recruited for the study. Exposure potential was estimated by dislodgeable foliar residue measurements, and individual exposures were estimated by biological monitoring through urinary metabolites. Measureable azinphos-methyl residues were found on apple foliage at all sites throughout the six-week sampling period, indicating continuous exposure potential (median residue level of 0.5 microgram/cm2). Measurable levels of the urinary dialkylphosphate metabolite, DMTP, were found in virtually all urine samples (limit of detection = 0.04 microgram/mL). Mean DMTP concentrations differed significantly across sites (0.53, 0.29, and 0.90 microgram/mL for Sites 1-3, respectively; analysis of variance, p < .002), and intraindividual variability was much greater than interindividual differences. Group mean DMTP concentrations at each site fluctuated according to foliar residue levels. Measurable DMTP concentrations were found in 9% of reference workers, ranging from 0.04-0.18 microgram/mL. Cholinesterase activity levels monitored with a field test kit were not considered reliable due to temperature changes of the instrument.

[Evaluation of urinary excretion of ethylenethiourea in subjects occupationally and non-occupationally exposed to ethylenebis(dithiocarbamates)]. / Valutazione dell'escrezione urinaria di etilentiourea in soggetti professionalmente e non professionalmente esposti ad etilenbisditiocarbammati.

Ethylenebisdithiorcabamate (EBDC) fungicides are broken down metabolically and in the environment to ethylenethiourea (ETU), a suspected carcinogen. Urinary ETU was assayed in control groups and subjects occupationaly exposed to EBDC and was found to be an excellent indicator of exposure both to ETU and EBDC. Correct use of protective clothing greatly reduced exposure and urinary excretion of ETU. ETU was excreted, albeit in low concentrations, in a high percentage (91% and 30%) of subjects in both control groups, demonstrating its utility as an indicator of widespread EBDC contamination.

Biological monitoring of deltamethrin in sprayers by HPLC method.

Using HPLC, the authors had investigated the three metabolites of deltamethrin (DM) in the urine of spraymen and one suicide, namely: dibromovinyl-dimethylcyclopropane carboxylic acid (Br2A), 3-phenoxybenzyl-hydroxy-ethyl acetate (PHE) and 3-phenoxyl-benzoic acid (BA). Br2A was chosen as the biological monitoring parameter for DM exposed people, and the urine samples of one suicide and 11 farmers sprayed DM or DM plus methamidophos were examined for Br2A quantitatively which was detected in 8 of 11 sprayers and in the suicide case.

Intervention studies against "green symptoms" among Indian tobacco harvesters.

The use of rubber gloves reduced nicotine and cotinine absorption among 29 tobacco harvesters, as evidenced by the urinary excretion rate of nicotine and cotinine. Approximately 20% (n = 6) of the subjects reported that symptoms disappeared when they used gloves, but the remaining 23 workers complained of an occasional headache even when using gloves. Wearing of boots and socks as well as gloves prevented the symptoms and significantly decreased nicotine and cotinine excretion. This suggests that nicotine is absorbed through the feet.

An epidemiological study on occupational acute pyrethroid poisoning in cotton farmers.

A cross sectional survey on the prevalence of acute pyrethroid poisoning in cotton farmers was conducted in 1987 and 1988. A total of 3113 pyrethroid spraymen (2230 men (71.6%) and 883 women (28.4%] were interviewed after spraying and followed up for 72 hours. Adverse effects of pyrethroid exposure were found in 834 of them (26.8%) manifested as abnormal facial sensations, dizziness, headache, fatigue, nausea, or loss of appetite. Only 10 subjects, who developed significant systemic symptoms and had signs of listlessness or muscular fasciculation, were diagnosed as having mild occupational acute pyrethroid poisoning with a prevalence of 0.31% in subjects exposed to pure pyrethroids and 0.38% in subjects exposed to pyrethroid organophosphate mixtures. Measurements of pyrethroid concentrations in the air of the breathing zone, in skin pads, and in urine samples showed that dermal contamination is the main route of exposure to pyrethroids in cotton growers. Preventive measures are recommended.

Levels of exposure and biological monitoring of pyrethroids in spraymen.

To assess the exposure response relation of pyrethroids in spraymen, 50 adult male cotton growers were selected and divided into three groups, one group to spray pyrethroids for one day, two groups to spray for three days. Deltamethrin, fenvalerate, and a deltamethrin methamidophos mixture were sprayed by appropriate subgroups for five hours a day. Exposure levels were evaluated by measuring the air concentration, dermal exposure concentration, and urinary content of pyrethroids by gas chromatography. Air concentrations of deltamethrin at the breathing zone were 0.01-0.89 microgram/m3 in the deltamethrin exposed group. For fenvalerate, air concentrations were 0.06-1.98 micrograms/m3. Dermal exposure, particularly on the legs, feet, and hands was appreciable and indicated that this was the main route of absorption. In those spraying for one day, urinary deltamethrin was not detectable by 12 hours after the beginning of exposure whereas fenvalerate was still detectable up to 24 hours after first exposure. Both pyrethroids could be detected two days after the end of three day spraying. Health effects were investigated by interview and physical examination. Twenty nine spraymen complained of abnormal facial sensations that developed mostly two to three hours from the start of pyrethroid spraying and that disappeared by 24 hours after exposure ceased. Some had dizziness, headache, and nausea, but no subject was diagnosed as having acute pyrethroid poisoning. The symptoms showed no significant correlation with urinary pyrethroid excretion. Blood cholinesterase activity of spraymen using the pyrethroid methamidophos mixture did not change.

Biological monitoring of human exposure to acephate.

Acephate is a water-soluble organophosphate insecticide whose action on insects has been related to its conversion to methamidophos, a very potent anticholinesterase agent which has caused delayed neuropathy in man. Inhalation and skin exposure to acephate was evaluated in four workers engaged in 8-day campaigns with the formulation of the 97%-pure technical product. Before, during, and after exposure, the workers were monitored for the urine content of acephate and methamidophos, and for erythrocyte (AChE) and plasma (PChE) cholinesterase levels. Median air concentrations (8-hr TWA) ranged from 0.278 to 2.170 mg/m3; median total-body skin deposition ranged from 26.1 to 41.9 mg/day. Based on these values, daily workers' absorption of acephate was estimated to be in the order of 10-20 mg. Urinary excretion of unchanged acephate followed a pattern consistent with exposure, showing peak values of excretion during the workshift or in the eight hr after the end of the workshift. The urine levels of unchanged acephate were found to vary from 1 to 10 mg/L. Methamidophos was not detected in any urine sample (detection limit: 30 micrograms/L). High correlation (r = 0.78) was found between skin exposure level and urine acephate elimination. No changes in AChE or PChE were observed for the workers whose urinary concentrations of acephate were 1 or 2 mg/L. One subject who had urinary acephate excretion between 3 and 8 mg/L, showed slightly decreased values of PChE during exposure and of AChE after exposure.