Carcinogenic, activity substances

For pharmacy practice this distinction between genotoxic and non-genotoxic carcinogenic substances is at the moment of little practical value, because only very few carcinogenic active substances have been defined as non-genotoxic. 

Health and Safety Factors. MSA is a strong toxic acid and is corrosive to skin. The acute oral toxicity of the sodium salt in mice LD q is 6.2 g/kg. The 1976 edition of the NIOSH Registry of Toxic Effects of Chemical Substances Hsts certain reaction products of MSA as having suspected mutagenic, teratogenic, and carcinogenic activity (410). 

The carcinogenic activity of chemical substances is important as well. They are present in pesticides of different classes OCPs (DDT, aldrine, heptachlor, methoxychlor), thiocarbamates (thiram, zineb, ziram), carbamides (monuron) [3], etc. Even if the official description of a given pesticide does not denote its carcinogenic (mutagenic, teratogenic, embryotoxic, etc.) activity, this merely means that this particular pesticide was not studied sufficiently. 

All known human carcinogens - the substances ranked by lARC as having been causally linked to human cancers - have been shown to be capable of inducing cancers in some (but not all) species of experimental animals, with the possible exception of arsenic. Arsenic is a human carcinogen, however it has not been adequately tested in animals - so it is perhaps not a real exception to the rule. A few examples of carcinogens that are known to be active in both humans and animals are presented in Table 6.4. 

Substitution in 98/8/EC is maintained indirectly though the application of comparative risk assessment, which is mandated in Article 10 of the directive. In order to include active substances in Annex I, lA or IB, several requirements have to be fulfilled. For example, active substances cannot be incorporated in the list if they are carcinogenic, mutagenic, toxic for reproduction, sensitising or bioaccumulative. 

Several short-term bioassay procedures (3-14) have been developed recently which are applicable to detecting mutagenic and potential carcinogenic activity of organic substances. The SaimoneJla/mammalian mlcrosome assay or Ames Test (13-13] has been the most frequently applied and its efficacy has been well documented. This assay has also been applied to complex mixtures (19-22) to reduce greatly the time... 

The identification of the carcinogenic potential of substances often requires the consideration of a large set of data. An important part of the assessment of the available data concerns the evaluation of the mode of action underlying the carcinogenic activity, as this information also allows an evaluation of possible human relevance, existence of thresholds, and comparability with stmcturaUy... 

It generally is agreed that cumene has no damaging effect on the hematopoietic system, despite its chemical similarity to benzene. Furthermore, cumene is not anticipated to be a significant carcinogenic hazard because it is metabolically similar to toluene, a substance that showed no carcinogenic activity in 2-year inhalation studies. ... 

Dickens F, Jones HEH Carcinogenic activity of a series of reactive lactones and related substances. Br J Cancer 15 85-100, 1961... 

The basic idea of the CLH process is the transfer of responsibility for classification and labeling from industrial companies to authorities on a European Community level. In case of active substances in biocidal or plant protection products, all intrinsic properties including physicochemical properties, human health hazards, and environmental hazards are subject to the harmonization. By contrast, in the case of chemicals which are used in other application fields only some specific hazard classes are considered in the CLH procedure. According to Article 36 of the CLP Regulation, these are respiratory sensitization, carcinogenicity, germ cell mutagenicity, and reproductive toxicity. Consequently, these provisions have... 

It is not possible on the basis of present knowledge of the relationship of chemical structure to the carcinogenic activity of a chemical to predict how many of the millions of compounds in nature, or the tens of thousands of compounds in commerce, are carcinogenic. Although relatively few chemicals have been observed to cause cancer in human populations, those that have (Thble 5.1), and the himdreds of other substances for which there is some evidence of carcinogenicity in laboratory animals (Thble 5.2), include compounds of widely diverse structures. 

The K-region of a polycyclic aromatic hydrocarbon is typified by the 9,10-bond of phenanthrene. According to the Schmidt-Pullman electronic theory, an unsubstituted K-region is a requirement for carcinogenic activity see A. Pullman and B. Pullman, La Cancerisation par les Substances Chimiques et la Structure Moleculaire, Masson, Paris, 1955. 

Examination of reproductive function, of embryo-fetal and perinatal toxicity of mutagenic potential and of carcinogenic potential must be considered. However, constituents other than the active substance(s) are incriminated, validation of their removal may replace the study. 

The second concept is that repeated doses of any substance will produce its toxic effects (with the exception of carcinogenicity) in 90 days or not at all. Thus, the lifetime "no effect" dose can be derived from the 90-day "no effect" dose. There are indications that even carcinogenic "activity" may be detected in short-term studies. 

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