Gaskin, SharynThredgold, LeighTefera, Yonatal Mesfin2022-06-102022-06-102021https://hdl.handle.net/2440/135389Problem statement Exposure to pesticides in agriculture constitutes a major occupational and public health concern. Worldwide, it has been estimated that over a billion people work in agriculture, and most use pesticides to protect their crops from insects and other pests. Every year, occupational exposure to pesticides has been associated with more than 385 million poisoning cases, over 200,000 deaths, and a range of adverse health outcomes. Greenhouses are enclosed structures with unique work environment characteristics, and the implication of these factors for occupational exposure to pesticides is a major area of interest. The use of personal protective equipment (PPE) such as gloves is among the key interventions to minimise pesticide exposure in greenhouses. The selection of suitable gloves remains a challenge and the chemical protection performance of gloves may be dependent on work environment factors such as temperature, which is of increasing concern in a warming climate. Organophosphate (OP) insecticides are among the most widely used classes of pesticides and the skin is the primary route of occupational exposure in horticulture. Thus, there is a need to understand dermal exposure and the glove permeation potential of this class of pesticides. Dermal exposure assessments used for pesticide regulatory decisions have focused mostly on the active ingredients (AI), largely ignoring the fact that workers in real-life encounter commercially available formulated products and the potential role of formulation coingredients. Gap analysis The following four research gaps were identified through reviewing the literature evidence addressed in this research. 1. Greenhouses have some unique characteristics that set them apart from traditional open field farms. However, little is known about the implications of these greenhouse characteristics and the interactions therein on occupational pesticide exposure. 2. Although different chemical-resistant gloves are recommended for handling pesticides in horticulture, the comparative performance of these gloves in warm to hot conditions is understudied. 3. Apart from work environment factors, physicochemical and formulation attributes of the pesticide product itself may influence dermal exposure as well as permeation through chemical resistant gloves. However, the nature and extent of dermal exposure and the relevance of physicochemical properties and skin permeability models in predicting dermal absorption of pesticides from commercial formulations remain unclear. 4. Although pesticides are often complex mixtures of one or more AI and several coingredients, most in vitro dermal exposure assessment studies have only focused on the AI. Very little is known about the role of formulation co-ingredients on dermal absorption and glove permeation potential of the active insecticides. Purpose statement The overarching purpose of this research is to understand how work environment and chemical risk factors influence occupational exposure to pesticides in horticulture. There are two primary aims of this research: 1) A critical literature review attempts to examine how greenhouse characteristics influence occupational exposure to pesticides, and 2) A series of laboratory-based experimental studies set out to understand the nature and extent of dermal exposure and glove protection against OP insecticides as commercial formulations. General research questions 1) What is the evidence on the risk factors of occupational exposure to pesticides in greenhouse work environments? 2) What is the significance of temperature and pesticide formulation factors in determining the extent of dermal exposure and glove protection performance against OP insecticides? Methodology A combination of a critical literature review and a series of laboratory-based experimental studies were conducted to answer the above research questions. These are summarised below. Critical literature review (Study 1) The critical literature review followed the “Work”, “Worker” and “Workplace” conceptual framework. The search strategy, the screening, and appraisal processes identified 71 relevant literature sources for the review. These research articles were categorised into four groups based on what each studied. 1. Studies that described pesticide exposure scenarios in greenhouses (n=38), 2. Studies that analysed the effect of “Work”, “Worker” and “Workplace” factors on pesticide exposure (n=20) 3. Studies that investigated pesticide fate and behaviour in greenhouses (n=8) 4. Studies that compared exposure between greenhouses and open farms (n=5) Laboratory-based dermal exposure and glove permeation studies (Studies 2, 3, and 4) Permeation studies (in vitro human skin and test cell glove permeation) were performed using OP insecticides selected on the basis of their common use in Australia. For all experiments, permeation tests involved at least two concentrations of OP insecticides: Spray dilution strength and mixing concentrate strength. These experiments informed the following three discrete but related studies. Study 2: Effect of temperature on comparative protection performance of gloves - A glove permeation study - Three glove materials: polyvinylchloride (PVC), nitrile butadiene rubber (NBR), and nitrile/neoprene (NN) - Two OP insecticides formulations: dimethoate and malathion - A range of temperature conditions: 25-60°C. Study 3: Dermal absorption of OP insecticides as formulations - In vitro human skin permeation study - Four OP insecticide formulations: acephate, dimethoate, malathion, and diazinon - Three skin permeability models (Potts & Guy, Mitragotri, and IHSkinPerm) were evaluated. Study 4: The role of formulation co-ingredients in dermal exposure to OP insecticides - In vitro human skin and glove permeation study - One glove material: PVC - Two OP insecticides - Dimethoate: pure and two commercial formulations (one with xylene and the other without xylene) Omethoate: pure and two commercial formulations with the main difference being the presence of the co-ingredient propylene glycol methyl ether acetate (PGMEA). - Temperature conditions: 37°C for skin and 35°C for glove experiments Major findings This research analysed the risk factors for occupational pesticide exposure in horticulture and the main findings are broadly discussed in two parts. In part 1, the influence of Work Environment risk factors such as greenhouse characteristics and temperature on occupational exposure to pesticides and glove protection performance is discussed. Part 2 outlines how Chemical risk factors (i.e. physicochemical properties and formulation co-ingredient compositions of pesticides) influence dermal absorption and glove protection. PART 1-WORK ENVIRONMENT RISK FACTORS Greenhouse work environment and pesticide exposure The critical literature review revealed a number of exposure modifying factors in greenhouses, which are broadly discussed within the “Work”, “Worker”, and “Workplace” conceptual framework. Workplace The greenhouse work environment is characterized by its enclosed nature, tight space, dense plant arrangements, and controlled micro-climatic parameters including light, humidity, temperature, and ventilation. The critical literature review revealed two mechanisms in which these greenhouse Workplace factors influence pesticide exposure parameters. Firstly, Workplace factors directly influence pesticide exposure parameters such as the fate, distribution, and availability of pesticides in greenhouses, bodily distribution of pesticides, and penetration of pesticides through protective clothes and gloves. Secondly, Workplace factors alter how theWork is done (e.g. type of pesticides used, type of spraying techniques/equipment used, and the frequency of contact with contaminated surfaces), and how Workers behave (e.g. potentially poor safety procedures and inadequate PPE use compliance). Work The major exposure modifying Work factors in greenhouses were intense workload, quick reentry interval, and predominantly manual spraying techniques. These were shown to influence occupational exposure parameters such as the duration, frequency, and route of exposure, the body part contaminated, and PPE-use compliance. Worker The majority of the literature describes greenhouse workers as under-educated, poorly trained, and socioeconomically disadvantaged migrant workforce with precarious personal circumstances. Although these Worker characteristics may increase workers’ vulnerability for pesticide exposure and risk, a systematic understanding of how these characteristics contribute to pesticide exposure in greenhouses is still lacking. Overall, the evidence presented in the literature suggests that most of the pesticide exposure modifying greenhouse characteristics and interactions therein may not be apparent in traditional open field systems. Therefore, the two environments could have different pesticide exposure scenarios and may have different health risks as well. Glove permeation of OP insecticides and temperature The effect of temperature on permeation resistance of each chemical resistant glove was shown to be significant, particularly at high exposure concentrations. A comparison of the three gloves reveals that there was no significant difference in permeation resistance when tested against dilute forms of dimethoate (0.3 g/l and 1.6 g/l) and Malathion (1 g/l) at 25ºC. However, there was a significant difference in permeation resistance between glove materials under the “worst-case” exposure scenario of handling highly concentrated formulation products of dimethoate (400 g/l) and malathion (1150g/l), at elevated temperatures. PVC gloves afforded the highest permeation resistance, followed by NBR glove and lastly the single-use NN glove material. PART 2: CHEMICAL RISK FACTORS Pesticide formulations are often complex mixtures of active insecticides and co-ingredients. The analysis of Chemical risk factors for occupational exposure to pesticides was possible in this research because commercially available pesticide formulations were used in skin and glove permeation experiments. This part was informed by two studies. The first examined skin permeation of OP insecticides as formulations while the second investigates the role of formulation co-ingredients on permeation through the skin and PVC gloves. Skin permeation of OP insecticides as formulations The purpose of studying skin permeation of OP insecticides as formulations was to determine the relevance of physicochemical properties and selected Quantitative Structure-Permeability Relationship (QSPR) models in predicting skin permeability of OP insecticides as formulations. In terms of physicochemical properties, higher permeation flux was recorded at a higher applied concentration of OP insecticides for the hydrophilic AI (acephate and dimethoate), but not for the lipophilic ones (malathion and diazinon). The tested skin permeability models (Potts & Guy, Mitragotri, and IHSkinPerm) mostly over-predicted experimental outcomes by several orders of magnitude. Models were much less accurate in predicting permeation from highly concentrated emulsions of the lipophilic compounds. The model predictions were accurate only on two out of seven occasions, and only for the hydrophilic OP insecticides. The role of formulation co-ingredients in dermal exposure to OP insecticides The findings showed that the presence of xylene in dimethoate formulation and presence of PGMEA in omethoate formulation plays a critical role in the permeation of the respective OP insecticides through PVC gloves at high mixing concentration. The omethoate formulation without PGMEA content, showed 184-fold greater cumulative permeation and more than 16 fold shorter breakthrough (BT) time. The presence of xylene in dimethoate formulation increased the cumulative permeation (by 1.5 fold) and decreased BT time (by an hour) of dimethoate. The influence of these co-ingredients on skin uptake within the exposure timeframe was not statistically significant at both high and low OP insecticide concentrations which may be due to the high degree of variability with skin experiments. Novelty and strength In all glove and skin permeation experimental studies included in this thesis, commercially available pesticide formulations of OP insecticides were employed in the context of their use in horticulture. Thus, this research is the first to report empirical skin/glove permeation data for most of the OP insecticides studied. The two major strengths of this research are 1) framing of experimental studies around real-world exposure scenarios within the context of Australian horticulture, and 2) the use of fresh human donated skin, which is considered a gold standard for in vitro dermal absorption studies. Limitations This research is largely informed by laboratory-based experiments, hence it may not capture all the factors that would influence exposure in the field. Despite its limitation, it was supplemented by a critical review that captured the exposure modifying factors in greenhouses. Conclusions and recommendations This thesis combines multiple pieces of evidence from a critical literature review and a series of laboratory-based experimental studies to extend our knowledge of pesticide exposure risk in horticulture. Based on the findings the following conclusions can be made: Firstly, the exposure-modifying effect of the greenhouse work environment may set it apart from traditional open field farming in terms of pesticide exposure and its risks. This necessitates the need for the development of tailored guidelines for pesticide exposure control in greenhouses. Secondly, it was demonstrated that not all recommended gloves are equally protective. The findings underpin the importance of considering temperature-induced glove performance reduction in testing, selecting, using, storing, and replacing glove materials if used under hot working conditions. Thirdly, the findings from the skin permeation study support the notion that skin permeability models derived from experimental data on aqueous solutions have limited applicability in accurately predicting dermal absorption of OP insecticides from commercial formulations. Fourthly, the findings suggest that the presence and proportions of co-ingredients play a critical role in glove permeation potential of undiluted OP insecticides, which confirms the relevance of considering permeation data of co-ingredients in glove selection and recommendation. Based on the evidence from this research, the following recommendations have been made for various stakeholders: - Glove manufacturers should extend standard glove permeation test conditions to incorporate commercial pesticide formulations, in-use temperatures, and pesticide concentration conditions. - Pesticide manufacturers and suppliers should consider the role of formulation coingredients for dermal exposure when specifying glove materials and when developing pesticide formulations. Pesticide regulatory agencies should consider the implications of formulation coingredients in the process of reviewing exposure data as well as making product approval and registration decisions. - Horticulture growers and workers handling concentrated products at elevated temperature conditions, such as in greenhouses, should be aware of the increased exposure risk, the temperature-induced glove performance reduction, and the need for more frequent replacement. - Occupational hygienists and other risk assessors should take caution when using skin permeability models, developed for aqueous solutions, to predict dermal absorption of chemicals as formulations, particularly for highly concentrated lipophilic chemicals. Further research could assess the comparative health risk between greenhouses and open field horticulture, and the effects of glove reuse and pesticide concentrations on dermal exposure. Research into the feasibility of co-ingredient modifications to minimise dermal exposure would also be a fruitful area for further work.enPesticides, Greenhouse Workers, Dermal Exposure, Glove Performance, Formulation ingredientsThesis