Hazardous substances sensitisation

Hazardous substances according to the European legislation are those substances with at least one H(azard)-state-ment . While preparing medicines or manipulating them, exposure to hazardous substances as such or as medicinal products can occur, which may cause a health risk. The types of toxicity (acute, chronic, carcinogenicity, teratogenicity, sensitisation, etcetera) together with the extent and route of exposure, determine the health risk. This chapter focuses on exposure via inhalation and skin contact. 

The dangerous properties of acute toxicity, irritation, corrosivity, sensitisation, repeated-dose toxicity and CMR are evaluated in terms of their potential toxic effects to workers, consumers and man exposed indirectly via the environment, based on the use for each stage in the lifecycle of the substance from which exposure can occur. Risk assessment is also required if there are reasonable grounds for concern for potential hazardous properties, e.g., from positive in vitro mutagenicity tests or structural alerts. The risk assessment involves comparing the estimated occupational or consumer exposure levels with the exposure levels at which no adverse effects are anticipated. This may be a quantitative risk assessment, based on the ratio between the two values, or a qualitative evaluation. The principles of human health risk assessment are covered in detail by Illing (a.30) and more briefly in Chapter 7 of (73). 

Hydroxypropyl methacrylate (HPMA) is labelled as irritant (Xi) in EC, including Denmark, while it is classified as a skin sensitiser in Sweden. Concentration limits for sensitising substances in formulations is 1%, and for irritant substances it is 10% before appropriate hazard labelling is required. Toxicological information used for these interpretations is derived from the same source. It may be hoped that such Scandinavian issues should start to resolve themselves when these EFTA countries combine with EC to form EEA. 

The 28 Adaptation to Technical Progress in relation to the European Dangerous Substances Directive (67/548/EEC), has now classified CIT/MIT in any preparation equal to or greater than 15 parts per million to be a sensitiser. Since many formulations will require more than 15 ppm of CIT/MIT, it will make it more difficult to use this chemistry (and not put hazard labels arising from CIT/MIT use) and achieve technical success. 

Hazards of substances can be acute, for example if a strong acid is spilled on the skin, or chronic, if long term exposure results in health damage, such as sensitisation or cancer. 

In an exceptional situation the actual exposure can be determined (see Sect. 26.5.3), the hazards of the substance has been defined sufficiently (see Sect. 26.3.5) and above all, the exposure limit to the substance has been set by the competent authority. This may apply for instance to working with ethanol, see also Sect. 26.7.2. In such an ideal situation it is possible to claim completely safe working conditions or, in case of genotoxic and sensitising substances, safe with a societally accepted minor health risk (see Sect. 26.7.2). In practice for pharmacy preparation and reconstitution medicines hardly any exposure limits exist at the moment. In most situations risk mitigation means ... 

Safety. Most countries have government guidelines on safe handling and use of chemicals, such as UK Health Safety Executive COSHH (control of substances hazardous to health), which is more focused on exposure risk. This can cause problems, such as when HSE issued a chemical alert about glutaraldehyde, and its potential for causing respiratory sensitisation. Immediately, several customers asked to change from glutaraldehyde to a different chemistry. 

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