Challenges and Opportunities for Occupational Epidemiology in the Twenty-first Century.

PURPOSE OF REVIEW: There are many opportunities and challenges for conducting occupational epidemiologic studies today. In this paper, we summarize the discussion of a symposium held at the Epidemiology in Occupational Health (EPICOH) conference, Chicago 2014, on challenges for occupational epidemiology in the twenty-first century. RECENT FINDINGS: The increasing number of publications and attendance at our conferences suggests that worldwide interest in occupational epidemiology has been growing. There are clearly abundant opportunities for new research in occupational epidemiology. Areas ripe for further work include developing improved methods for exposure assessment, statistical analysis, studying migrant workers and other vulnerable populations, the use of biomarkers, and new hazards. Several major challenges are also discussed such as the rapidly changing nature and location of work, lack of funding, and political/legal conflicts. As long as work exists there will be occupational diseases that demand our attention, and a need for epidemiologic studies designed to characterize these risks and to support the development of preventive strategies. Despite the challenges and given the important past contribution in this field, we are optimistic about the importance and continued vitality of the research field of occupational epidemiology.

Intervention to reduce heat stress and improve efficiency among sugarcane workers in El Salvador: Phase 1.

BACKGROUND: Chronic heat stress and dehydration from strenuous work in hot environments is considered an essential component of the epidemic of chronic kidney disease in Central America. OBJECTIVE: (1) To assess feasibility of providing an intervention modelled on OSHA's Water.Rest.Shade programme (WRS) during sugarcane cutting and (2) to prevent heat stress and dehydration without decreasing productivity. METHODS: Midway through the 6-month harvest, the intervention introduced WRS practices. A 60-person cutting group was provided water supplied in individual backpacks, mobile shaded rest areas and scheduled rest periods. Ergonomically improved machetes and efficiency strategies were also implemented. Health data (anthropometric, blood, urine, questionnaires) were collected preharvest, preintervention, mid-intervention and at the end of harvest. A subsample participated in focus group discussions. Daily wet bulb globe temperatures (WBGT) were recorded. The employer provided individual production records. RESULTS: Over the harvest WBGT was >26°C from 9:00 onwards reaching average maximum of 29.3±1.7°C, around 13:00. Postintervention self-reported water consumption increased 25%. Symptoms associated with heat stress and with dehydration decreased. Individual daily production increased from 5.1 to a high of 7.3 tons/person/day postintervention. This increase was greater than in other cutting groups at the company. Focus groups reported a positive perception of components of the WRS, and the new machete and cutting programmes. CONCLUSIONS: A WRS intervention is feasible in sugarcane fields, and appears to markedly reduce the impact of the heat stress conditions for the workforce. With proper attention to work practices, production can be maintained with less impact on worker health.

Organochlorine chemicals and neurodegeneration among elderly subjects in Costa Rica.

BACKGROUND: We previously screened 400 elderly Costa Ricans for neurodegenerative disease. Those reporting occupational pesticide exposure (18%) had an increased Parkinson׳s disease (PD) risk (OR 2.57, 95% CI 0.91-7.26), and worse cognition (Mini-Mental States Exam (MMSE) 24.5 versus 25.9 points, p=0.01). We subsequently measured long-lasting organochlorine pesticides (ß-HCH, DDE, DDT, and dieldrin) in a sub-sample (n=89). Dieldrin and ß-HCH have been linked to PD, and DDE to Alzheimer׳s disease. METHODS: We ran regression models for MMSE and tremor-at-rest to assess associations with pesticides in 89 subjects. RESULTS: The percent of ß-HCH, DDE, DDT (parent compound for DDE), and dieldrin above their limit of detection (LOD) were 100%, 93%, 75%, and 57%, respectively. Tremor-at-rest was found in 21 subjects, and the mean MMSE was 25. Those who reported occupational pesticide exposure (n=36) had more detectable dieldrin samples (p=0.005), and higher mean levels of dieldrin (p=0.01), than those not reporting exposure. Other pesticides did not differ between those with and without self-reported occupational exposure. There was a positive but non-significant trend of higher risk for tremor-at-rest with higher dieldrin (p=0.10 for linear trend). Neither DDE nor DDT showed a relationship with MMSE. However, after excluding two outliers with the lowest MMSE scores, higher DDT levels showed some modest association with lower MMSE (p=0.09 for linear trend). CONCLUSIONS: Our data are limited by small sample size. However, dieldrin was high in our population, has been previously linked to PD, and could be partly responsible for the excess PD risk seen in our population.

Occupational pesticide exposure and screening tests for neurodegenerative disease among an elderly population in Costa Rica.

BACKGROUND: Pesticides have been associated with Parkinson's disease (PD) in many studies, and with Alzheimer's disease (AD) in a few. METHODS: We conducted screening tests for neurologic disease and occupational pesticide use in a population-based sample of 400 elderly subjects at two government-run clinics in Costa Rica; 361 subjects who failed the initial screen were given both the mini-mental states exam (MMSE) and a modified version of a 10-item united Parkinson's disease rating motor subscale (UPDRS). Among subjects who failed either test, 144 were then examined by a neurologist. RESULTS: Past occupational pesticide exposure was reported by 18% of subjects. Exposed subjects performed worse on the MMSE than the non-exposed (mean 24.5 versus 25.9, p=0.01, adjusted for age, sex, and education). The exposed had significantly elevated risks of abnormal scores on two UPDRS items, tremor-at-rest (OR 2.58, 1.28-5.23), and finger-tapping (OR=2.94, 95% CI 1.03-8.41). Thirty-three (23%) of those examined by the neurologist were diagnosed with possible/probable PD, 3-4 times the expected based on international data; 85% of these cases had not been previously diagnosed. Among subjects who took the UPDRS, the exposed had an increased risk of PD (OR=2.57, 95% CI 0.91-7.26). No excess risk was found for a diagnosis of AD or mild cognitive impairment. CONCLUSIONS: Elderly subjects with past occupational pesticide exposure performed significantly worse on screening tests for dementia and PD, and had an increased risk of an eventual PD diagnosis. Screening may be particularly appropriate among elderly subjects with past pesticide exposure.

Suicide and exposure to organophosphate insecticides: cause or effect?

BACKGROUND: Suicide using pesticides as agent is recognized as a major cause of pesticide poisoning. METHODS: A literature review of mortality and morbidity studies related to suicide among pesticide-exposed populations, and of human and animal studies of central nervous system toxicity related to organophosphate (OP) pesticides was performed. RESULTS: Suicide rates are high in farming populations. Animal studies link OP exposure to serotonin disturbances in the central nervous system, which are implicated in depression and suicide in humans. Epidemiological studies conclude that acute and chronic OP exposure is associated with affective disorders. Case series and ecological studies also support a causal association between OP use and suicide. CONCLUSIONS: OPs are not only agents for suicide. They may be part of the causal pathway. Emphasizing OPs solely as agents for suicide shifts responsibility for prevention to the individual, reducing corporate responsibility and limiting policy options available for control.

Muscular strength and vibration thresholds during two years after acute poisoning with organophosphate insecticides.

AIMS: To evaluate the association of acute organophosphate (OP) poisoning with chronic sensory and motor neurological impairment. METHODS: This study concerns the third of a series of three examinations of hand strength and vibration thresholds in a two year period after acute OP poisoning among 48 Nicaraguan men. The first two examinations were performed at hospital discharge and seven weeks after poisoning, and the present examination two years later. Twenty eight cattle ranchers and fishermen who had never experienced pesticide poisoning were examined as controls, also three times over the two year period. The poisonings were categorised as caused by "non-neuropathic" OPs and "neuropathic" OPs, each subdivided in moderate and severe poisonings. RESULTS: Men poisoned with OP insecticides had persistent reduced hand strength. We previously reported weakness at hospital discharge for OP poisoned in all categories that worsened seven weeks later for those severely poisoned with neuropathic OPs. Strength improved over time, but the poisoned were still weaker than controls two years after the poisoning, most noticeably among the subjects most severely poisoned with neuropathic OPs. Also, index finger and toe vibration thresholds were slightly increased at the end of the two year period, among men with OP poisonings in all categories, but patterns of onset and evolvement of impairment of vibration sensitivity were less clear than with grip and pinch strength. CONCLUSIONS: Persistent, mainly motor, impairment of the peripheral nervous system was found in men two years after OP poisoning, in particular in severe occupational and intentional poisonings with neuropathic OPs. This finding is possibly due to remaining organophosphate induced delayed polyneuropathy.

Experiences from long-term research cooperation between Costa Rican, Nicaraguan, and Swedish institutions.

This paper summarizes experiences from long-term ongoing cooperation between Swedish research institutions and institutions at the National Universities in Nicaragua and Costa Rica. 24 researchers and teachers from the Central American institutions and ten Swedish research students have been trained. In addition to three full doctoral and three licentiate (two-year PhD program) theses, the two programs have so far published 15 articles in English-language, international, refereed journals and about three times as many abstracts for conferences in more than ten countries. A "sandwich" model for training is recommended, where the southern researchers come to the wealthier partner for collaborative analyses and write-ups of the publications, while spending 50-75% of their time in their home countries for data collection. Such collaboration should be planned for a time span of at least eight years and include substantial numbers of researchers and students. Means to minimize the risk of brain drain are suggested. The collaboration has been important for the globalization of the research cultures at the participating institutions and has trained international experts.

Pesticide-related illness and injuries among banana workers in Costa Rica: a comparison between 1993 and 1996.

An intervention program considerably decreased systemic poisonings on banana plantations in Costa Rica in the early 1990s. Nevertheless, pesticide safety continues to be controversial. To examine the determinants of acute pesticide-related illness on banana plantations, the authors surveyed occupational injuries and illness among banana workers in the Atlantic Region of Costa Rica that were reported during 1993 and 1996 to the National Insurance Institute. Incidence rates were calculated for categories of pesticides and types of medical problems, for all and subgroups of banana workers. Between 1993 and 1996, an overall 35% decrease in injuries was observed, attributable to a marked decline in topical injuries (3.3 vs 1.9 per 100 workers), whereas systemic poisonings remained the same (0.7 per 100 in both years). The decrease concerned selectively milder skin conditions, indicating underreporting of less severe health effects. In both years, paraquat was the pesticide most frequently associated with injuries, mostly skin and eye lesions. Workers at highest risk per unit time of exposure were nematocide applicators, herbicide applicators, and cleaners of packing plants. Despite control measures, further reduction of systemic illness had not been achieved. The decrease of topical injuries may be partly explained by improved work conditions, but possible underreporting hinders interpretation. Pesticide-related illness on banana plantations is a persistent problem.

Chronic nervous-system effects of long-term occupational exposure to DDT.

Dichlorodiphenyltrichloroethane (DDT) is a compound with moderate toxicity that is judged to be safe for occupational use, although little is known about its long-term effects on the human nervous system. We investigated chronic nervous-system effects of long-term occupational exposure to DDT by comparing the neurobehavioural performance of retired malaria-control workers with a reference group of retired guards and drivers. DDT-exposed workers did worse on tests assessing various neurobehavioural functions than controls; performance significantly deteriorated with increasing years of DDT application. Our results could not be explained by exposure to cholinesterase-inhibiting pesticides or other potential confounding factors.

Risk of pancreatic cancer in workers exposed to chlorinated hydrocarbon solvents and related compounds: a meta-analysis.

This is a meta-analysis of occupational exposures to chlorinated hydrocarbon (CHC) solvents and pancreatic cancer, based primarily on studies that addressed exposure directly (agent studies) and secondarily on studies that reported data without verification of individual CHC exposures (job title studies), all of which were listed in databases for the period January 1969 to May 1998. Standardized extraction of data and double-checking of consistency of data extraction by five extractors were done. Simple random models estimated meta-relative risks. Suggestive weak excesses were found for trichloroethylene (meta-relative risk (MRR) = 1.24, 95% confidence interval (CI): 0.79, 1.97), polychlorinated biphenyls (MRR = 1.37, 95% CI: 0.56, 3.31), methylene chloride (MRR = 1.42, 95% CI: 0.80, 2.53), and vinyl chloride (MRR = 1.17, 95% CI: 0.71, 1.91) but not for carbon tetrachloride. One study addressed tetrachloroethylene (MRR = 3.08, 95% CI: 0.63, 8.99); another investigated chlorohydrin production (MRR = 4.92, 95% CI: 1.58, 11.4). Exposure-response meta-analyses for trichloroethylene and methylene chloride failed to reveal trends. Job title studies on metal degreasing and dry cleaning revealed significant MRRs (2.0 and 1.4, respectively). Publication bias was unlikely. Confounding may have remained insufficiently controlled. Unless the results are seriously biased by exposure or endpoint misclassification or by confounding, strong causal associations between CHC compounds and pancreatic cancer can be judged unlikely. Interactions between environmental and occupational agents, lifestyle factors, and genetic susceptibility remain a possibility, but the data for this meta-analysis did not address interactions.

Time trends of occupational pesticide-related injuries in Costa Rica, 1982-1992.

To evaluate time trends of occupational pesticide-related injuries in Costa Rica, a survey was carried out three times over a ten-year period at a national reporting system for occupational accidents and diseases among wage-earning workers. The sample comprised the accidents reported during the months of June of the years 1982, 1987, and 1992. The overall incidence rates were 1.8, 2.7, and 2.5 per 1,000 agricultural workers, respectively. Rates among female workers increased (3.1, 3.7, 5.4) and were elevated as compared with male workers (1.7, 2.6, 2.3). The trend for topical lesions was upgoing (1.2, 1.4, 2.1), consistent with an increased use of fungicides and lack of safety measures for pesticides with low acute toxicity. Systemic poisonings peaked in 1987 (0.6, 1.2, 0.5), declining in 1992 with increased use of biologic pest control and pyrethroid insecticides less toxic than cholinesterase inhibitors, and improved safety during nematocide applications on banana plantations. In 1992, despite the largest decline of systemic poisonings in the banana-producing Atlantic Region, poisonings as well as topical injuries were still four times more frequent in this region than in the rest of the country. Restriction of highly toxic pesticides together with implementation of occupational safety measures can reduce systemic poisonings in developing countries. Such policies need to be extended to other pesticides to prevent less life threatening but often disabling skin and eye injuries.

Paraquat in developing countries.

The herbicide paraquat is considered safe by industry and the bulk of regulators worldwide. However, determinants of exposure from 30 years ago persist in developing countries. Little is known about systemic absorption from occupational exposures. The relationships between exposure determinants, levels of external exposure, biomarkers of exposure, and outcomes are not clear. High rates of severe acute poisonings have been documented. In addition, topical injuries occur in as many as 50% of exposed workers. Non-worker populations are also at risk, particularly children. Long-term and delayed health effects include Parkinson's disease, lung effects, and skin cancer. Regulatory agencies have not fully recognized either the inherent toxicity of paraquat or the particular risks derived from exposures in developing countries. Independent risk assessment in the developing-country context and application of the precautionary principle are necessary to prevent adverse effects of dangerous pesticides in susceptible populations.

Pesticide-handling practices in agriculture in Tanzania: observational data from 27 coffee and cotton farms.

The practices of pesticide handling in agriculture were surveyed in 1991-1993 in Tanzania, to identify hazardous practices and farms where they occurred. The study involved 23 coffee farms with 246 persons exposed to hazardous practices, and four cotton farms with 45 exposed. An observation form addressed locations of important places with respect to pesticide spraying, storage, disposal, and equipment; personal protection; and hygiene. More pesticide formulations were used for coffee compared with cotton and by individual rather than cooperative farms. Coffee farms more often had unlabeled pesticide containers and missing mixing instructions, while cotton pesticides were stored in bedrooms, near food, and near open fires, and pesticide leftovers were often present. Hazardous practices were more pronounced at individual than cooperative farms, with significant differences in pesticide storage areas, as well as unlabeled and non-original containers. The study demonstrated the need to train farmers in pesticide safety, strengthen advisory and regulatory services, and extend protection to farm workers' families.

Hazardous pesticides in Central America.

Pesticides are an extensively documented occupational and environmental hazard in Central America. Yet, severe problems persist. Toxic pesticide use in the Region increased during 1985-1999. High exposure levels and ineffectiveness of personal protective equipment evidence the difficulties for risk reduction. Acute poisonings remain a severe problem. Delayed and/or long-lasting health effects include dermatoses, cancer, and genotoxic, neurotoxic, and respiratory effects. The use of hazardous pesticides persists through deficiencies in government-driven assessment and risk management; excessive focus on regional harmonization; short-term economic interests; strong links between industry and governments; aggressive marketing; weak trade unions; and failure of universities to reach decision makers. Regulation based on local data is lacking. An agreement of the Ministries of Health for restricting the most toxic pesticides in Central America has potential for progress. The most effective way to reduce risk is to greatly reduce pesticide use. Actions needed include development of multidisciplinary strategies for local studies on health and environmental impact of pesticides; development of sustainable nonchemical agricultural technologies; evaluation of interventions; extending and sharing of expertise within the Region; strengthening of unions and communities; and redefining the role of industry toward development of safer products, with responsible marketing and reliable information.

Occupational exposures and pancreatic cancer: a meta-analysis.

OBJECTIVES: Consolidation of epidemiological data on pancreatic cancer and worksite exposures. METHODS: Publications during 1969-98 were surveyed. Studies without verified exposures were excluded. Meta-analyses were conducted on data from 92 studies covering 161 populations, with results for 23 agents or groups of agents. With a standard format, five epidemiologists extracted risk estimates and variables of the structure and quality of each study. The extracted data were centrally checked. Random meta-models were applied. RESULTS: Based on 20 populations, exposure to chlorinated hydrocarbon (CHC) solvents and related compounds was associated with a meta-risk ratio (MRR) of 1.4 (95% confidence interval (95% CI) 1.0 to 1.8). Nickel and nickel compounds were considered in four populations (1.9; 1.2 to 3.2). Excesses were found also for chromium and chromium compounds (1.4; 0.9 to 2.3), polycyclic aromatic hydrocarbons (PAHs) (1.5; 0.9 to 2.5), organochlorine insecticides (1.5; 0.6 to 3.7), silica dust (1.4; 0.9 to 2.0), and aliphatic and alicyclic hydrocarbon solvents (1.3; 0.8 to 2.8). Evidence on pancreatic carcinogenicity was weak or non-positive for the following agents: acrylonitrile (1.1; 0.0 to 6.2); arsenic (1.0; 0.6 to 1.5); asbestos (1.1; 0.9 to 1.5); diesel engine exhaust (1.0; 0.9 to 1.3); electromagnetic fields (1.1; 0.8 to 1.4); formaldehyde (0. 8; 0.5 to 1.0); flour dust (1.1; 0.3 to 3.2); cadmium and cadmium compounds (0.7; 0.4 to 1.4); gasoline (1.0; 0.8 to 1.2); herbicides (1.0; 0.8 to 1.3); iron and iron compounds (1.3; 0.7 to 2.5); lead and lead compounds (1.1; 0.8 to 1.5); man-made vitreous fibres (1.0; 0.6 to 1.6); oil mist (0.9; 0.8 to 1.0); and wood dust (1.1; 0.9 to 2.5). The occupational aetiological fraction of pancreatic cancer was estimated at 12%. In a subpopulation exposed to CHC solvents and related compounds, it was 29%; to chromium and chromium compounds, 23%; to nickel and nickel compounds, 47%; to insecticides, 33%; and to PAHs, 33%. CONCLUSION: Occupational exposures may increase risk of pancreatic cancer. High quality studies are called for on interactions between occupational, environmental, and lifestyle factors as well as interactions between genes and the environment.

Collaboration between developing and developed countries and between developing countries in occupational health research and surveillance.

Collaborative occupational health and safety studies between counterparts in developing and developed countries and between developing countries have demonstrated their potential for improving occupational health and safety. Such collaboration in occupational health and safety is encouraged in the development of infrastructure in research empowerment and capacity building. This action includes the setting of priorities, the identification and documentation of problems, sponsorship, data bases and surveillance systems, technical support, methodology, publishing, research and training programs, controlled intervention, information exchange, and networking. Examples of priorities in occupational health and safety in the developing world include the informal sector (informally hired and independent workers), temporary work, pesticides, accidents, dusts, carcinogens, solvents, ergonomics, women and child labor, human immunodeficiency virus/acquired immunodeficiencey syndrome (HIV/AIDS), and transfer of hazardous materials and technologies. The sustainability of occupational health and safety structures and functions in the developing countries is a primary concern. Socioethical principles emphasize local, national, mutual and global gains. Examples of collaboration are given. Pervasive problems and strategies toward their solution are highlighted.

Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure.

BACKGROUND: This study describes geographical differences in cancer incidence in Costa Rica, and investigates if some of these differences may be related to pesticides. METHODS: Data were combined from the cancer registry (1981-1993), the 1984 population census, the 1984 agricultural census, and a national pesticide data set. The 81 counties of Costa Rica were the units for the ecological analyses. Adjacent counties were grouped into 14 regions (3 urban and 11 rural) with relatively similar socioeconomic characteristics. County indices for population density and agricultural variables were constructed and categorized. Differences across regions and categories were assessed by comparing observed numbers of incident cases to expected values derived from national rates. Within the tertile of most rural counties, rate ratios between categories of high and low pesticide use were calculated. RESULTS: In urban regions, excesses were observed for lung, colorectal, breast, uterus, ovary, prostate, testis, kidney, and bladder cancers; and in rural regions for gastric, cervical, penile, and skin cancers. Skin cancers (lip, melanoma, non-melanocytic skin and penile cancer) occurred in excess in coffee growing areas with extensive use of paraquat and lead arsenate. In the most rural subset, heavy pesticide use was associated with an increase of cancer incidence overall and at a considerable number of specific sites, including lung cancer (relative risk [RR] 2.0 for men and 2.6 for women) and all female hormone-related cancers (RR between 1.3 and 1.8). CONCLUSIONS: Regions and populations at high risk for specific cancers were identified. Several hypotheses for associations between pesticides and cancer emerged. The findings call for studies at the individual level.

Unintentional fatal paraquat poisonings among agricultural workers in Costa Rica: report of 15 cases.

This study analyzes the exposure circumstances of 15 fatal occupational paraquat poisonings. To evaluate the potential danger of dermal absorption and the amount needed to produce a fatal outcome in the event of oral intake, we reviewed the medical records and autopsy protocols and interviewed relatives. Five fatalities were due to ingestion of a mouthful of paraquat concentrate, and five to intake of a smaller amount; three cases were associated with dermal exposure, and in two, there was no evidence of either oral or dermal exposure. Several cases concerned diluted paraquat spray. The clinical and pathomorphological findings, including a "blinded" evaluation of lung slides, were consistent with paraquat poisoning in all cases. Difficulties in establishing the diagnosis and recognizing the exposure were identified, as well as classification of unintentional poisonings as suicides at autopsy. The findings suggest that paraquat may cause fatal poisonings by ingestion of small amounts, by dermal absorption of diluted paraquat, and possibly by inhalation. More conclusive studies are warranted.

Agricultural pesticide use in developing countries: health effects and research needs.

Large worker populations in the Third World are exposed to increasing amounts of pesticides, including pesticides severely restricted and banned in industrialized countries. Studies on knowledge, attitudes, and practices indicate that unsafe use of pesticides is the rule in Third World countries. Surveys of acute poisonings show high rates in these countries, despite underregistration. The scarce studies on chronic health outcomes demonstrate neurotoxic, reproductive, and dermatologic effects. Exposure assessment consists mainly of cholinesterase testing, and few studies have quantified dermal and respiratory exposure. The few intervention studies demonstrate the need for evaluation of the impact of preventive measures and policies. There is no evidence that widespread "safe-use" programs have greatly affected exposure and morbidity. It was concluded that research should focus on simple methods for surveillance of exposure and on surveillance of acute illness and its causes in order to develop and evaluate rapid local interventions. Studies on chronic effects should be carried out in selected countries, aiming at long-term and broader interventions. Policies that promote the use of pesticides should be critically evaluated. North-South and South-South research collaborations must be encouraged to address this global health problem.