Masterstudiengang "Drug Regulatory Affairs"
Assessment of nitrate, nitrite and nitrosamine exposure resulting from food, medicine intake, chemical and environmental contamination
Dr. Esther Hindricks (Abschlußjahr: 2020)
In 2018, the contamination of drugs with nitrosamines which are likely very potent human carcinogens has shown some potential shortcomings in the regulatory framework for medicinal products in spite of the respective guideline ICH M7 having come into force in 2016. The consequences of nitrosamine detection in medicinal products have pointed out the need for improvement of the regulatory framework, especially for the so called „cohort of concern”. As a consequence, fundamental conditions have been set in order to ensure a high quality of medicinal products and to protect human health. Nevertheless, the current detection of nitrosamines in medicinal products led to the question how other potentially nitrosamine-polluted sources are regulated?
Beside medicine intake the human population can be burdened with substances from daily nutrition which in combination with the human organism can lead to the development of nitrosamines, as well. Key components are nitrates and nitrites from food, drinking water, chemicals or from the environment which can be considered as precursors for nitrosamines formations under special circumstances.
The regulatory framework for medicinal products, food, drinking water and chemicals differs in essential key points. Medicinal products need to be authorized, whereas chemicals need to be at least registered. In contrast to this food neither requires an authorization nor registration by an authority to be placed on the market. The differences in the regulatory frameworks are also reflected in consumer protection limits and assessment methods (e.g. "As Low As Reasonably Achievable (ALARA)" - principle, "Benchmark dose lower confidence limit 10 % (BMDL10)" approach or "Tumour incidence of 50 % (TD50)" approach) of different authorities for nitrate, nitrite and nitrosamines.
Thus, the regulatory framework, risk evaluation methods and consumer protection limits are described and discussed in detail in this master thesis. Furthermore, proposals have been made to improve the respective regulatory frameworks for future and to keep protection of human health at high level.