Substance genotoxic

Recently, 202 and 203 were found to significantly reduce the mutation frequency induced by BaP in vivo as well (00UP3). Previously, flie same group had pointed out that some genotoxic effects could result from UV irradiation of tryptophan, but this had not been attributed to lipophilic substances like 202 and 203 (94MI5). 

The carcinogenic potential of the profiled substance is qualitatively evaluated, when appropriate, using existing toxicokinetic, genotoxic, and carcinogenic data. ATSDR does not currently assess cancer potency or perform cancer risk assessments. Minimal risk levels (MRLs) for noncancer end points (if derived) and the end points from which they were derived are indicated and discussed. 

Ethylene oxide is used in the manufacture of raw materials and can be used to sterilize the surface of finished products and containers. Unfortunately, ethylene oxide is a genotoxic carcinogen and its use is not accepted without justification. In any event, tight controls are required on residues of ethylene oxide and its halohydrin-related substances. For raw materials the amount of these residues is limited to 1 and 50 pig/g, respectively for finished products 1 and 50 pg/g, respectively (with any affected ingredients subject to the control limits for raw materials) and for containers, based on simulated use, 1 and 50 pg/mL container volume, respectively. 

De Marco A, De Simone C, D Ambrosio C, Owczarek M (1999) Buthionine sul-foximine prevents the reduction of the genotoxic activity of maleic hydrazide by soil humic substances in Vicia faba seedlings. Mutat Res 438 89-95... 

Pyrethrins (I) Pyrethrins induce the formation of liver and thyroid tumors by mechanisms that appear to be similar to those of other non-genotoxic, mitogenic substances, e.g., phenobarbital, which produce tumors in rodents, and these tumors are not predictive of hazard in humans at relevant exposures [99]... 

Mutagenicity and carcinogenicity are generally considered to be non-threshold effects, unless a non-genotoxic mechanism can be established with a NOEL (or NOAEL or LOAEL). Risk assessment is based on establishing whether exposure is prevented. A similar process of preventing exposure also applies for skin and respiratory sensitisers, since there is no means of identifying a dose or concentration below which adverse effects will not occur in someone already sensitised to a particular substance. 

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. 

A full set of studies normally includes short-term and long-term animal studies on chronic effects and potential carcinogenicity, studies on reproductive and developmental toxicity, genotoxicity, kinetics and metabolism, pharmacological properties and special studies depending on the characteristics of the substance and observation in the standard set of studies. Human clinical studies may be necessary for substances which are metabolised and may interfere with functions of the human body. 

Absence of carcinogenity, genotoxicity, developmental and reproductive toxicity and of chronic toxicity effects at low exposure levels are indispensable prerequisites for food additive approvals. All substances approved in the European Union or the USA or deemed generally recognised as safe (GRAS) in the USA fulfil this requirement. 

Cancer. No studies have been conducted in human populations to determine whether mirex or chlordecone causes cancer. However, studies in mice and rats have demonstrated the ability of mirex to cause liver tumors (Innes et al. 1969 NTP 1990 Ulland et al. 1977a), pheochromocytomas (NTP 1990), and rare renal tumors (NTP 1990). A study in mice and rats also showed the ability of chlordecone to increase liver tumors (NC11976). As indicated above, available data on the genotoxicity of mirex and chlordecone indicate that these chemicals do not cause cancer by a mutagenic mechanism but rather by tumor promotion. Both mirex and chlordecone are considered by the DHHS to be substances that may reasonably be anticipated to be carcinogens and by IARC to be possible human carcinogens. EPA has not classified mirex or chlordecone as to their carcinogenicity. 

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