In this dissertation, based on the conducted comprehensive theoretical and experimental studies, the methodological aspects of regulating harmful effects of chemical substances in the workplace air of the pharmaceutical enterprises and the procedure for developing analytical methods for controlling the levels of air pollution with active pharmaceutical ingredients have been improved and harmonized with the European legislation. In addition, the ways of implementing contractual obligations and practical introduction of the European expertise in the field of occupational health protection have been identified.
It has been shown that the basic principles of the European and domestic legislative frameworks in the field of labor protection measures against exposure to hazardous chemicals are identical and oblige employers to assess the safety risks for employees. The scope of regulatory procedures, i.e. maximum permissible concentrations of chemical substances, is almost identical in both EU and Ukraine, but the baseline procedure in EU countries is identified as the average concentration of a substance per work shift, while in Ukraine maximum one-time concentration is applied.
The key hazardous chemical factor of pharmaceutical production is the inhalation exposure to active pharmaceutical ingredients, i.e. substances with high biological activity. 16 hygiene regulations and methods for measuring the concentration of 19 active pharmaceutical ingredients in the workplace air have been developed. It has been demonstrated that specific and long-term effects of active pharmaceutical ingredients in the case of pharmaceutical production differ from the nature of their pharmacological actions and side effects. According to the acute oral toxicity parameters, bismuth citrate, cyanocobalamin, mebhydrolin, acyclovir, hydrocortisone acetate, meldonium, inosine pranobex belong to low-risk substances; L-lysine aescinate, procaine hydrochloride, ethyl 2-bromo-3-methyl-butanoate, antral, loratadine, desloratadine, nitroxoline are moderately dangerous substances; diphenhydramine hydrochloride and naphazoline nitrate belong to Hazard Class II and are highly hazardous substances. Bismuth citrate, antral, loratadine, mebhydroline, hydrocortisone acetate are prone to excess cumulative effect or have strong cumulated activity.
Recommendations for improving the methodological support to the development of regulations for the permissible concentrations of active pharmaceutical ingredients in the workplace air include the increase of the evidence for the threshold chronic effect of substances and indicate the need for further development of exclusively maximum permissible concentrations. The latter, in turn, must necessarily include the average concentrations of a substance per work shift and, if necessary and taking into account the specifics of exposure, maximum one-time concentrations.
The list of priority hazardous chemical factors of pharmaceutical production includes 122 active pharmaceutical ingredients, five of which are implemented from the lists approved by EU directives.
In the course of regular medical examinations aimed at timely identification of early signs of acute and chronic occupational diseases (poisoning) in employees of pharmaceutical enterprises, it is necessary to take into account pharmacological and toxic effects of active pharmaceutical ingredients that are used as raw materials in such production. In this regard, the medical professional of the relevant field should be involved and appropriate laboratory and functional studies should be conducted.
