Carcinogens Directive

Compliance with the Carcinogens Directive requires the employer to assess the risk of exposure, and the nature and degree of that risk. The hierarchy of control mechanisms, in descending order of preference, is ... 

EEC. Council Directive on the protection of workers from the risks related to exposure to carcinogens at work (Carcinogens Directive), Off. J. Eur. Commiss., L.196, 26-07-90. 

The principles set out in the Directive (also found in the Carcinogens Directive -see below) are based on substitution, prevention, protection and control. 

In Annex II an overview on the transposition in each country of the main pieces of European legislation dealing with hazardous chemicals and workers protection is p ovided. In Aimex m, are found the names and the source of llie basic legtslation, trani sing the Framework Directive (89/391/EEC), the Chemical Agents Directive (98/24/EC), and the Carcinogen Directive (2004/37/EC) into national law in each country. A link to a web page where the most recent OEL list can be found is also provided (if existent). 

Directives dealing with the issues of occupational safety and health are based on article 137 of the Treaty and define, in contrast to the first mentioned Directives, only the minimum standard. National legislation is allowed to require additional obligations. Representative examples are the agent directive 98/24/EC [1-8] and the carcinogen directive 2004/37/EC [1-9]. 

Within the legislation of the dangerous materials, the chemical carcinogens are of special interest, and therefore the carcinogen Directive [2-4] has to be considered. In general, the following can be distinguished ... 

The European Framework Directive on Safety and Health at Work (Directive 89/391/EEC [72]) provides the fundamentals of European safety and health legislation. On the basis of the Framework Directive nearly twenty individual directives have been developed, covering a range of risk factors and different categories of workers [73], for example the Carcinogens Directive (see Sect. 26.6.4) and the Pregnant Workers Directive (see Sect. 26.6.5). The OSH Framework Directive continues to apply in full to all the areas covered by the individual directives, but where individual directives contain more stringent and/or specific provisions, these special provisions of individual directives prevail. 

The Carcinogens Directive is the origin of two notions in pharmaceutical practice the ALARA (as low as reasonably achievable) principle at the processing of carcinogenic substances and the registration of working with carcinogenic substances. 

Halogenated compounds, found in high concentrations in seaweeds consumed in Japan and Hawaii, have been suspected of being carcinogenic, largely based on epidemiological extrapolation (high incidences of hepatic carcinoma). However, direct human causation has not been estabUshed (107). 

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

Nitration. Naphthalene is easily nitrated with mixed acids, eg, nitric and sulfuric, at moderate temperatures to give mostly 1-nitronaphthalene and small quantities, 3—5%, of 2-nitronaphthalene. 2-Nitronaphthalene [581-89-5] is not made in substantial amounts by direct nitration and must be produced by indirect methods, eg, the Bucherer reaction starting with 2-naphthalenol (2-naphthol [135-19-3]). However, the 2-naphthylamine [91-59-8] made using this route is a carcinogen thus the Bucherer method is seldom used in the United States. 

It is not appropriate to generali2e the carcinogenicity of this class of compounds. Nitrofura2one appears to increase the incidence of benign mammary tumors in rats. The tumorigenic activity of fura2ohdone is expressed by an increase in the incidence of spontaneous tumors in both mice and rats. Bioassays of nitrofurantoin in several species of mice and rats failed to reveal any evidence of direct tumorigenic activity. Ovarian tumors have been reported in B C F mice, but these are beheved due to an indirect expression of toxicity (14,15). 

In the European Union, coal-derived complex chemical substances, ie, those contained in the European Inventory of Existing Commercial Chemical Substances, have been classified for carcinogenicity in the twenty-first adaptation to technical progress of the European Commission (EC) Dangerous Substances Directive 1994 67/548/EEC (57). The EC Regulation 793/93 requires data sets to be submitted by producers or importers to the... 

Direct dyes are defined as anionic dyes substantive to ceUulosic fibers (cotton, viscose, etc), when applied from an aqueous bath containing an electrolyte. Before the discovery of Congo Red in 1884, only mordanted cotton could be dyed. Congo Red [573-58-0] (62) (Cl Direct Red 28 Cl 22120) a primary symmetrical disazo dye, which is made readily from bisdiazotized benzidine and naphthionic acid [84-86-6] (4-arnino-l-naphthalenesulfonic acid), was the precursor of a most important line of dyes, including all shades, derived from benzidine and its homologues. Today, no benzidine dye is produced because benzidine is carcinogenic. 

EEC Directive on the protection of workers from the exposure from carcinogens at work... 

For carcinogens, risks are estimated as the incremental probability of an indii idual developing ameer o er a lifetime as a result of exposure to the potential carcinogen. The slope factor (SF) converts estimated daily intakes averaged over a lifetime of exposure directly to incremental risk of an individual developing cancer. 

Considerable studies are required to establish the toxicological profile of the drug substance. These must assess its direct toxic effects, together with its potential as a reproductive toxin, mutagen, or carcinogen. 

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