CARCINOGENIC REPROTOXIC

So the term hazardous substances may have different notions. In this chapter the CLP definition is followed meaning that all substances are considered potentially hazardous. Carcinogenic, reprotoxic and mutagenic substances are either noted as such or as a group as CMR. Occupational safety and health care investigates all processes and all substances, to prevent health damage of workers. 

The National Institute for Occupational Safety and Health (NIOSH) of the United States describes in the section Determining whether a drug is hazardous how human and animal data on carcinogenicity, reprotoxicity and genotoxicity are interpreted for their list of hazardous substances [8]. 

Results of CMR (Carcinogenic, Mutagenic, Reprotoxic) tests and statement on endocrine disrupting potential. 

More qualitative indicators are also useful absorption through healthy skin, irritation to skin, eyes, and respiratory system, together with sensitization with the following indicators carcinogenic, mutagenic, teratogenic, reprotoxic, and so on. These properties can be summarized by indication of a toxicity class. 

For instance, as reported by two interviewees, current Health and Safety Executive (HSEO priorities are based on statistics for carcinogenicity, respiratory illnesses and skin disease to the exclusion of mutagenic or reprotoxic effects. 

Nevertheless, the statistics presented in Table 4.5 must be interpreted with caution. As the evidence in Section 4.4.1 suggests, the comparatively low frequency of fatalities and low lost injury time in the UK and Sweden may be attributable to regulators in these two countries prioritising more readily identifiable effects of exposure to certain hazards (e.g., carcinogenicity or sensitisation) over less apparent effects (in terms of existing epidemiological studies or occupational health incident reports) that result from exposure to other hazards (e.g., reprotoxicity). 

Social mobilisation appears to be initiated by (i) the potential hazardous properties of a substance, regardless of exposure or (ii) the exposure of vulnerable groups (e.g., children or elderly) to a chemical, regardless of hazard. Reporting commonly used household products as containing potentially carcinogenic or potentially reprotoxic ... 

Automatic bans for carcinogenic, mutagenic or reprotoxic (CMR) substances following the restrictions procedure under Directive 76/769 have been excluded (step 2) because these will continue to apply under REACH. The result of the risk criteria evaluation for each substance according to the decision-making matrix is shown in Table 6.1 (step 3). Based on the selection procedure detailed in Section 5.3.2, the most suitable regulatory outcome... 

Authorisation. The use of chemicals considered to be of very high concern would be subject to authorisation. The aim is for such chemicals to be phased out and substituted, unless industry can show that the use presents negligible risk or that it is acceptable, taking into account its socioeconomic benefits, the lack of safer chemicals and measures to minimise exposure. Chemicals of very high concern are likely to include carcinogens, mutagens or reprotoxic substances (CMRs), particularly persistent, bioaccumulative and toxic substances. 

Fatty Acid Salts (Soaps [82]) Negative, in vitro Considered safe as is part of the human diet Not carcinogenic Not reprotoxic... 

A result of the risk assessments was that DEHP, DBP and BBP are toxic for reproduction. Accordingly, they were classified as CMR (carcinogen, mutagen, reprotoxic) substances, category 2 which is reflected in the classification and labelling with R-phrases 60-62 (Tables 12, 13). 

Amide waxes like stearamide, oleamide, erucamide are subject to extensive risk assessments under the existing chemicals HPV programme in the USA [169]. The available data indicate that there is no mutagenic or reprotoxic potential identified. Repeated dose feeding studies up to 2 years did not reveal a carcinogenic effect. The NOFL was determined to be >7,500 mg kg body weight/day. 

Preparations share the classifications used for substances, but the allocation is dependent either on the results of tests (except for those aimed at carcinogenic, mutagenic, and reprotoxic endpoints) or upon calculations using concentration limits. Unless specific concentration limits are given when the EU agrees the environmental classification for a substance, default concentration limits apply. Those which will apply when the Directive is amended are summarised in Table 6.8. 

The definition of hazardous in combination with substances follows the European Occupational Safety and Health legislation i.e. every substance that has been assigned a so-called H(azard)-statement. Carcinogenicity, Mutagenicity or Reprotoxicity (CMR) are reflected in specific H-statements, but many other types of toxicity exist. This approach should diminish the confusion that arises when hazardous is considered synonym with CMR or, in other situations, even with CMR plus some specific types of toxicity. Let alone if hazardous substances is considered synonym with the therapeutic class of antineoplastics. 

However, the use of the term hazardous substances with regard to pharmacy preparation and recraistitution, is often restricted to carcinogenic, mutagenic and reprotoxic substances. Radiopharmaceuticals and gene therapeutics may be counted under this term as well. The National Institute of Occupational Safety and Health of the US (NIOSH) however also counts substances with a high chronic toxic potential to hazardous substances , see further Sect. 26.3.3. 

Hazard type EU listed as carcinogenic and reprotoxic. Many public OELs exist, for instance 260 mg/m (TWA-8 h) and 1,900 mg/m (TWA-15 min) in the Netherlands. 

A relevant therapeutic group of active substances, handled aseptically, are parenteral antineoplastics. Many are classified as very toxic for the operator, mainly because of carcinogenicity and reprotoxicity [17], see also Sect. 26.3.3. Therefore, if antineoplastics are involved in aseptic handling, requirements are not only to protect the product against contamination of micro-organisms, but also to protect the operator and the environment from the product. The first measure however is a working procedure to minimise exposure to antineoplastics. This involves... 

Conventionally, a safety factor of 100 is used which incorporates a 10-fold factor for interspecies differences and a further 10-fold factor for inter-individual differences. This safety factor would be appropriate for endpoints relating to e.g. reduced growth rate in a sub-chronic study. However, for endpoints relating to teratogenicity anA/ or reprotoxicity, the safety factor, depending on the severity of the endpoint could be approximately 200 500 of the NO(A)EL. For carcinogenic substances the safety factor increases yet further to 1000. 

Solvent guides can also be used to flag legislative issues, such as category lA and IB carcinogenic, mutogenic or reprotoxic (CMR) solvents, or substances that deplete the ozone layer. ... 

According to European council directive 1999/38/EC, any solvent with the H350 (carcinogenic) or H360 (reprotoxic) hazard phrase in the Globally Harmonized System (GHS) of Classification and Labelling of Chemicals must be substituted, or have their use justified. 

Worker safety (acute and chronic exposure effects, toxicity, carcinogenicity, mutagenicity, reprotoxicity, skin absorption, sensitization, etc.)-... 

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