Occupational exposure to organophosphorus pesticides: exploratory case studies of factors influencing glove performance and skin penetration

Abstract

Problem statement: The widespread use of organophosphorus pesticides (OPs) in agriculture and urban pest control has seen significant morbidity and mortality. They are the most important cause of severe toxicity and death from acute poisoning worldwide, with more than 200,000 deaths each year in developing countries. OPs act to inhibit acetylcholinesterase in the nervous system, and may elicit acute and long term health effects. Some commercially available OPs are also classified as Chemicals of Security Concern by the Australian Government and are subject to special restrictions and surveillance. Occupational exposure may occur in manufacture, storage, transport, usage, disposal and in emergency situations. For example, ambulance workers may be exposed when attending accidental or intentional OP poisonings. The profiles may vary from short term high exposures for emergency personnel, to long term low exposures for farming communities. The World Health Organisation and a range of other agencies have determined that the continued use of these chemicals represents an important public and occupational health issue. A major route of exposure is skin absorption, and the use of protective chemical gloves is recommended, especially for the concentrated product. Safety data sheets (SDS) are meant to provide the user with information on appropriate glove protection. However, the concentrates are typically formulated products with solvents and additives that may influence the glove permeation behaviour of the active ingredient. Testing by glove manufacturers is rarely with the formulated product, and pertains to room temperature experiments with new gloves. Cheap or disposable gloves may not have been tested. In addition, the effects of elevated temperature, abrasion and ultraviolet (UV) exposure are poorly understood. Although these environmental factors are likely to be present in Australian workplaces, there is scant evidence of their practical significance to inform risk assessment and interventions, including glove selection and use. Apart from gloves, skin uptake may be influenced by high ambient temperatures. The limited dermal toxicological research literature suggests that skin penetration rates may be dramatically increased, with concomitant increases in health risk. Compounding the problem is the situation where chemical is occluded between glove and skin. Gap analysis: Based on a review of the occupational hygiene literature, knowledge gaps exist in three areas, relating to glove performance and skin penetration. Firstly, suppliers and formulators of agricultural OPs recommend the use of long length polyvinyl chloride (PVC) gloves. Indeed, distributors stock cheap versions of such gloves, but as they are not considered disposable, repeated use is the norm. Scientific uncertainty exists as to the protection afforded under real world conditions of solar radiation, elevated temperature and abrasion. Secondly, the chemical barrier performance of disposable gloves, as worn by ambulance workers in poisoning episodes, has not been investigated. Thirdly, it is known that skin absorption of chemicals depends on physicochemical properties such as molecular size and water solubility. However, there appear to be no skin penetration studies which have compared a range of OPs of different properties. Moreover, the studies that have been conducted have often used a finite dose model. An infinite dose model is more applicable for worst case occupational risk assessment. Purpose statement: This research aims to provide a better understanding of dermal exposure to OPs (under simulated real world conditions) and to generate data useful for predictive dermal risk assessment models and optimising control measures. It is anticipated that the improved evidence base will assist in reducing morbidity and mortality from OPs. A case study approach will be used, addressing both routine users and those in an emergency setting. Broad Research Questions: The following questions were developed from a literature review and context scoping from fieldwork observations. 1. How do the recommended PVC gloves (unused, exposed to UV and abrasion) perform against OPs in various exposure conditions? 2. What are the effects of different variable conditions on the barrier performance of different types of disposable gloves worn by ambulance workers and is the current practice suitable? 3. How is skin penetration affected by physicochemical properties of OPs, concentration of Ops and elevated temperature? Methodology: Four OPs widely used in Australia (omethoate, mevinphos, dichlorvos and diazinon) with differing physicochemical properties (e.g. octanol-water partition coefficient) were investigated. Tests were conducted at the full strength formulation (relevant for transport and mixing activities) and application strength (relevant for spraying), and at two temperatures. In the glove permeation studies, American Society for Testing and Materials (ASTM) permeation cells were used at two temperatures (room temperature and 45°C). Two case study scenarios were used, namely agricultural workers and ambulance workers. For Case Study 1 two brands of elbow length PVC gloves recommended for handling OPs were tested in new unused condition, and following UV exposure or abrasion. In Case Study 2 disposable nitrile and neoprene gloves used by South Australia Ambulance Service (SAAS) workers were tested individually and in combination (as per current practice). In the skin studies, human abdominal skin samples (heat separated epidermis) were exposed to the OPs (infinite dose) in static Franz cells according to OECD protocols for up to 8 hours, at room temperature and 37°C. Analysis for the OPs in both glove and skin experiments was undertaken using HPLC and UV detection. Main Findings: Glove performance tests – Case Study 1 Differences were noted in breakthrough time and cumulative penetration at the end of the 8-hour experiments for the two PVC glove brands. In general, PVC gloves performed well against the four tested OPs. Full strength formulations had shorter breakthrough times and greater cumulative permeations. Breakthrough of diazinon did not occur unless at full strength at 45°C (120 – 180 mins). In contrast, breakthrough of dichlorvos was observed for all exposure conditions (between 60 to 240 mins) except for application strength at room temperature. Mevinphos, which was only tested at room temperature, demonstrated breakthrough only for one brand of gloves. In the case of omethoate, breakthrough was noted from 60 minutes onwards. Permeation was uniformly higher at 45°C compared to room temperature. Gloves exposed to UV light (approximately equivalent to a week or more of extreme sunlight) or abrasion (5% thickness reduction) exhibited a small reduction in performance. Glove performance tests – Case Study 2 In glove performance tests on gloves used by SAAS workers, disposable nitrile and neoprene gloves demonstrated good protection against the four tested OPs in 4-hour experiments. In general, the thicker neoprene gloves demonstrated longer breakthrough times than nitrile gloves. At higher test concentration (full strength) of the four tested OPs, cumulative penetration at 8 hrs increased, and this was observed at both test temperatures. Elevated temperature to 45°C shortened the breakthrough time (between 5 and 20 minutes) and resulted in greater cumulative penetration of the OPs. Combining the disposable gloves (nitrile on neoprene) as practised by SAAS workers demonstrated better protection with longer breakthrough times and lower cumulative penetration of the tested OPs, compared to individual gloves. In vitro skin studies Dichlorvos was found to rapidly penetrate the skin. Elevated temperature and higher OP concentration resulted in faster penetration rate and increased cumulative penetration of the tested OPs. Comparison of the skin penetration data with Acceptable Daily Intakes (ADIs) of the respective OPs showed that ADIs may be exceeded rapidly, with the order being dichlorvos, diazinon, omethoate and mevinphos. Novelty of the research: This research uses an experimental design based on real life scenarios. Unlike most glove permeation and skin penetration studies this research used formulated OP products that are commercially available in the market. All experiments were conducted using an infinite dose model to simulate the worst exposure scenario (prolonged skin contamination from spills and splashes), and thus to establish the maximum penetration rates for risk assessment. Similarly, tests were conducted at elevated temperatures and with gloves exposed to ultraviolet (UV) and abrasion to mimic the common exposure conditions in real world scenarios. Implications: The research has highlighted the importance of elevated temperature, and the dermal risks associated with dichlorvos. The increased barrier protection afforded by double gloving (combining relatively polar and non-polar materials), for OPs of different physico-chemical properties, was shown. This is reassuring for ambulance workers who may encounter a range of OPs. Surprisingly, the influence of UV exposure and abrasion on the performance of the thick PVC gloves was found to be relatively minor, under the conditions examined. Data on the influence of physicochemical properties, concentration, and temperature are useful for refining dermal risk assessment models, and for worker education. On a broader public health level, the findings will allow a more rational use of gloves as chemical protective clothing to protect the population at risk from the danger of agricultural chemicals. Conclusions and Recommendations: The data indicate that the use of concentrated OPs in warmer conditions will greatly increase skin uptake. Dichlorvos demonstrated rapid and extensive skin penetration, but the data for all the tested OPs suggest that toxicologically important uptake can occur in relatively short time periods without skin protection. Glove permeation also increases with concentration, temperature, UV and abrasion. The practice of double gloving by ambulance workers is supported by the evidence. Following these exploratory studies, it is recommended that more glove permeation tests be conducted under realistic exposure scenarios. The findings should be compiled in a database for advisory purposes and made publicly accessible. Warnings for potential ADI exceedance should be included on labels or SDSs of the OP products to alert the users of the risks when handling OPs. Where changes may be made in the OP formulation by manufacturers, the suitability of glove recommendations should be reviewed.