Carcinogenicity, Genotoxicity, and Teratogenicity

Renwick considered that in relation to carcinogenicity for non-genotoxic chemicals and teratogenicity, the application of an extra factor for nature of toxicity is difficult to justify scientifically. He concluded that if a safety factor for nature of toxicity is to be used then logically it should be apphed to the NOAEL for the toxicity, which resulted in its use. For example, in relation to teratogenicity, a factor for nature of toxicity should be applied to the NOAEL for teratogenicity and not for maternal toxicity or some other endpoint. For carcinogenicity, the extra factor should be applied only to the NOAEL for the detection of tumors in those studies where this effect was the rationale for the use of an extra factor. In relation to a steep dose-response, it was concluded that this, in reality, concerns the precision of the NOAEL and therefore relates to the adequacy of the database rather than nature of toxicity. 

The mycotoxin ochratoxin A (AAA) (7), which is a possible human carcinogen, continues to receive extensive attention due to its presence in a myriad of foods and beverages (1520, 1521) and its well-established toxicity (teratogenicity, mutagenicity, immunotoxicity, genotoxicity, and carcinogenicity) (1522-1524). Major sources of ochratoxin A are grapes, must, and wine (1525-1533), cereals (1534), beer (1535,1536), dried fruit (1537), roasted coffee (1538), and cocoa products and chocolate (1539). 

The details of several other toxicological tests (namely, repeated-dose toxicity, subchronic toxicity, chronic toxicity, genotoxicity, mutagenicity, teratogenicity, carcinogenicity, neurotoxicity, and ecotoxicology) and the methods, purposes, and importance of safety evaluation studies to achieve human health have been discussed... 

No data are available to assess the mutagenic or genotoxic, carcinogenic, and teratogenic potential of this agent. 

PAs are ester alkaloids derived mainly from the necines retronecine and otonecine. They are carcinogenic, mutagenic, genotoxic, fetotoxic, and teratogenic. 

An additional assessment factor, of up to 10, has been apphed in some cases where the NOAEL has been derived for a critical effect, which is considered as a severe and irreversible effect, such as teratogenicity or non-genotoxic carcinogenicity, especially if associated with a shallow dose-response relationship. The principal rationale for an additional factor for nature of toxicity has been to provide a greater margin between the exposure of any particularly susceptible humans and the dose-response curve for such toxicity in experimental animals. 

Because of their diversity of chemical structures and differing physical properties, mycotoxins exhibit a wide array of biological effects on mammalian systems and individual mycotoxins can be genotoxic, mutagenic, carcinogenic, embryotoxic, teratogenic or oestrogenic (Smith and Henderson, 1991). Some... 

Class 2 solvents Solvents to be limited. These include non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity, such as neurotoxicity or teratogenicity and solvents suspected of other significant but reversible toxicities. 

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