Hazardous substances mutagenicity

Detection of toxicity, mutagenicity, or pathogenicity by conventional methods or by fast biotechnological tests. Production, trade, or use of specific products containing nonbiodegradable hazardous substances may be banned based on biotechnological tests of biodegradability and toxicity. 

Ideally, a full data set should be available for the hazard assessment of a chemical substance, including animal tests to evaluate the toxicokinetics and the following toxicological properties acute toxicity, irritation, sensitization, toxicity following repeated exposure to the substance, mutagenicity and genotoxicify, carcinogenicity, and effects on fertility and fetal development. 

The conventional approach to controlling releases of hazardous substances involves establishing safe levels for specific substances that allow environmental quality objectives and associated standards to be set and licence conditions or fixed emission limits to be determined. Environmental safe levels take account of the toxicity of the substance, its persistence and ability to bioaccumulate, and in some cases can include mutagenicity, carcinogenicity and reproductive impairment. Whitehouse and Cartwright (1998) discuss the need for environmental standards and identify the following purposes ... 

European Chemicals Bureau (http //ecb.jrc.it/) and the Hazardous Substance DataBank (http //toxnet.nlm.nih.gov/). When insufficient data were available for human chronic toxicity, a prediction of the carcinogenic and mutagenic effects was performed with the OSIRIS tool, available at the Organic Chemistry Portal (http // www.organic-chemistry.org/prog/peo/). 

The Safety Officer, after receiving the R D process description, immediately consults the appropriate literature to determine if any hazard exists relative to the toxicity or irritability of a particular product or intermediate. Material Safety Data Sheets, when available, are his prime source of information. In their absence, he consults the supplier of either the material or process for further information. If no information is available, he submits samples for toxicity screening, if it appears warranted. He may arrange testing for irritation, mutagenicity (Ames Test) or other hazards. Once all chemical toxicity information is available, he is responsible for judging its relative severity. He also recommends suitable protective equipment to be used by manufacturing personnel to avoid contact with a potentially hazardous substance. 

Mutagens alter DNA to produce inheritable trails. Although mutation is a natural process that occurs even in the absence of xenobiotic substances, most mutations are harmful (Manahan, 2000). The mechanisms of mutagenicity are similar to those of carcinogenicity and mutagens often cause birth defects as well. Therefore, mutagenic hazardous substances are of major toxicological concern. 

Precautions Deadly poison by swallowing or skin contact. Human mutagen (changes inherited characteristics). In 1985 over 150 people in California exhibited toxic effects from eating watermelons contaminated with aldicarb. FDA permits limited use. On EPA Extremely Hazardous Substances list. 

Furthermore, the employer has to reduce the use of carcinogens and mutagens as far as technically possible. The preferred method is substitution, which means replacement of hazardous substances, preparations, or processes with alternatives... 

Toxicology LD50 (oral, rat) 730 mg/kg extremely hazardous substance poison by ingestion, intravenous routes severe eye irritant can cause liver and kidney damage mod. allergen mutagenic data Hazardous Decomp. Prods. Heated to decomp., emits very toxic fumes of NOx, NH3, Cl"... 

Synonyms 3- [4-(4-Chlorophenoxy) phenyl]-1,1-dimethylurea 3-(p-(p-Chlorophenoxy) phenyl)-1,1-dimethylurea Empirical C15H16CIN2O2 Properties Cryst m.w. 290.77 Toxicology LD50 (oral, rat) 3700 mg/kg, (skin, rat) > 3 g/kg LC50 (inh., rat, 6 h) > 1350 mg/m mod. toxic by ing. mutagen TSCA listed Environmental Nontoxic to fish Precaution EPA extremely hazardous substances list... 

Safety/Toxicity Cytotoxicity, carcinogenicity,22 chronic toxicity,25 environmental toxicity,2 genotoxicity,25 hazardous substance,2 hematological effects,22 immunotoxicity,2 marine toxicity, 2 mutagenicity,5o neurotoxicity, phytotoxicity, soil toxicity, testicular effects ... 

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. 

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. 

Vanadium in addition causes corrosion problems, e.g. in the combustion chamber of power plants, and inhalable dusts or aerosols of nickel that might be generated during combustion of oil are classified as hazardous substances owing to their carcinogenic and mutagenic effects. 

Toxic air pollutants are pollutants which are hazardous to human health or the environment but which are not specifically regulated by the CAA. These pollutants are typically carcinogens, mutagens, and teratogens. The CAAA of 1977 failed to result in substantial reductions in the emissions of these harmful substances. 

Meanwhile the first tranche of the registration is done for all chemicals with a market volume of more than 1,000 Mg/a and for chemicals which have a high concern out of hazardous reasons (e.g., carcinogenic, mutagenic, or toxic to reproduction (CMR)). By the REACH deadline of 30 November 2010 for the first tranche, 24,675 registration dossiers were submitted for 4,300 substances including nearly... 

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). 

A survey is made of European Union directives regulating the use of hazardous chemicals and other industrial materials. A list is presented of carcinogenic, mutagenic and genotoxic substances covered by Directive 97/10/ CE. 

Human exposure to migrating substances (e.g., di(2-ethylhexyl)phthalate) may result in reproductive disorders. There is a hazard that vinyl chloride monomers or bisphenol A migrating into food may induce carcinogenic, mutagenic, and teratogenic episodes. 

It helps them to reduce systematically their use of hazardous chemicals and develop new products. Some companies have agreed on substances that need to be avoided. As documented In the case studies In Annex I of this report, they are Instructing their suppliers to phase out a range of carcinogenic, mutagenic and reproductive toxins, as well as some persistent, bloaccumulative, and endocrine disrupting chemicals. 

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