Национальные регистры и перечни химических веществ : преимущества и подходы к созданию

Целью настоящей публикации является описание подходов к созданию национальных регистров химических веществ и преимуществ их наличия для улучшения рационального регулирования химических веществ. Требования международных организаций могут направлять и влиять на обсуждение регистров химических веществ, равно как на понимание их роли в выполнении задач на национальном и международном уровнях. В публикации содержатся примеры национальных регистров и перечней, включая информацию о процессе их создания, содержании и сфере их применения, которые могут быть использованы при планировании аналогичной деятельности. Настоящая публикация была подготовлена в рамках проекта “Разработка законодательной и операционной основы для сбора и обмена информацией об опасных химических веществах в Грузии”, осуществляемого Европейским региональным бюро ВОЗ (2015-2017).

The general base in the thymidylate synthase catalyzed proton abstraction.

The enzyme thymidylate synthase (TSase), an important chemotherapeutic drug target, catalyzes the formation of 2'-deoxythymidine-5'-monophosphate (dTMP), a precursor of one of the DNA building blocks. TSase catalyzes a multi-step mechanism that includes the abstraction of a proton from the C5 of the substrate 2'-deoxyuridine-5'-monophosphate (dUMP). Previous studies on ecTSase proposed that an active-site residue, Y94 serves the role of the general base abstracting this proton. However, since Y94 is neither very basic, nor connected to basic residues, nor located close enough to the pyrimidine proton to be abstracted, the actual identity of this base remains enigmatic. Based on crystal structures, an alternative hypothesis is that the nearest potential proton-acceptor of C5 of dUMP is a water molecule that is part of a hydrogen bond (H-bond) network comprised of several water molecules and several protein residues including H147, E58, N177, and Y94. Here, we examine the role of the residue Y94 in the proton abstraction step by removing its hydroxyl group (Y94F mutant). We investigated the effect of the mutation on the temperature dependence of intrinsic kinetic isotope effects (KIEs) and found that these KIEs are more temperature dependent than those of the wild-type enzyme (WT). These results suggest that the phenolic -OH of Y94 is a component of the transition state for the proton abstraction step. The findings further support the hypothesis that no single functional group is the general base, but a network of bases and hydroxyls (from water molecules and tyrosine) sharing H-bonds across the active site can serve the role of the general base to remove the pyrimidine proton.

Indicators as a tool for the evaluation of effective national implementation of the Globally Harmonized System of Classification and Labelling of Chemicals (GHS).

This paper briefly outlines the United Nations Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and what is meant by GHS implementation in terms of policy-related information for decision-makers plus a framework of actions to enable such policies to be effectively undertaken. The paper discusses the need for simple indicators to measure progress with GHS implementation. Two groups of indicators have been described that comprehensively reflect basic components of GHS implementation. The first group was presented as aggregated indicators or indices, for national capability evaluation. Indicators to evaluate management performance linked to stated objectives were presented as the second group. Information from an Organisation for Economic Co-operation and Development (OECD) published questionnaire on GHS implementation and a questionnaire by the Intergovernmental Forum on Chemical Safety (IFCS) on chemical safety that included GHS have provided the basic information for applying the management capability indicators approach. Through the use of information in these two questionnaires, country-relevant and regional progress with GHS implementation was illustrated. Despite the GHS implementation target of 2008 set by the Johannesburg Plan of Implementation, very few countries have reported they have achieved this target. The simple management indicators proposed in this paper are based on adoption of a questionnaire and a numerical scoring system that could be used to chart progress towards GHS implementation. It was concluded, therefore, that the use of indicators as described in this paper does provide a quick survey of the overall situation in a country and facilitates comparison between countries across regions in terms of GHS implementation. Furthermore such results may indicate which countries require additional assistance with GHS implementation thus strengthening policies and actions across all sectors and involving governments, business, trade, and civil society.