This contribution deals with the understanding of pesticide exposure situations encountered by farmers during the use of vineyard sprayers. In order to better understand these situations, this work aims at identifying and understanding a specific chain of determinants based on analysis conducted at different levels: the treatment activities, the activities of sprayer design, the regulation that applies to this design and the activities of regulation development. The ergonomic analysis of treatment activities highlights the fact that farmers encounter many issues during the use of their equipment, which leads, in most cases, to situations of pesticides exposure. To that extent, the design of sprayers turns out to determining in the emergence of these situations. Indeed, the analysis of the design activities show that design choices reflect a lack of understanding of the winegrowers’ activity and the associated risks of pesticide contamination. Although regulation requirements could serve as a resource to include health and safety matters in the design, the analysis of their content reveals the same deficiencies. The analysis of the activities of rules development shows that the economic criterion holds a predominant position, sometimes at the expense of other criteria such as health and safety. The results of these analyses highlight the role played by design and regulation, as macrodeterminants, in the emergence of pesticide exposure situations during the use of sprayers. By considering a wider environment than that of the work situation, the chain of determinants investigated makes it possible to consider changes at different levels in order to aim at a sustainable prevention.