Class I carcinogen

Cumulative distributions of the logarithms of NOELs were plotted separately for each of the stmcmral classes. The 5th percentile NOEL was estimated for each stmctural class and this was in mrn converted to a human exposure threshold by applying the conventional default safety factor of 100 (Section 5.2.1). The stmcmre-based, tiered TTC values established were 1800 p,g/person/ day (Class I), 540 pg/person/day (Class II), and 90 pg/person/day (Class III). Endpoints covered include systemic toxicity except mutagenicity and carcinogenicity. Later work increased the number of chemicals in the database from 613 to 900 without altering the cumulative distributions of NOELs (Barlow 2005). 

Specified class I designated chemical substances 12 substances (carcinogenic substances among the class I designated chemical substances)... 

In general, four types of cabinets are used for work with research quantities of chemical carcinogens. These are the conventional fume hood a Class I biological safety cabinet a Class II (Type B) biological safety cabinet and a Class III closed glove box system (8). 

The facility must be designed to control access. Signs should designate restricted areas. Clothing requirements for entry should be identified. There should be directional air control with adequate ventilation rates. Primary containment equipment such as chemical fume hoods, a Class I or Class II (Type B) biological safety cabinet, or a glove box system should be available for use with known or suspect chemical carcinogens or other toxic substances. 

Class I solvents with proven or potential carcinogenic properties, and solvents hazardous to the environment, such as benzene, 1,2-dichloroethane, 1,1-dichloroethane, and carbon tetrachloride. These solvents should not be used in the pharmaceutical industry. If they have to be used, then their levels in pharmaceutical products must be monitored, and they cannot exceed ICH guidelines (Table 8.2) [9]. 

Class I solvents Solvents to be avoided. These include known human carcinogens, strongly suspected human carcinogens and environmental hazards, e.g., benzene, carbon tetrachloride and 1,2 dichloroethane. 

Short-term genotoxicity tests, including bacterial and mammalian cell assays, are widely used to assess potential carcinogenicity of chemical and physical agents, owing to the prominent role of genetic effects in the initiation and promotion of cancer however, the predictive value of such tests is far from absolute (114). Of the carcinogens listed as class I substances, Cr(Vl)... 

With regard to carcinogenicity, benzene has long been recognized as carcinogen in man. It is the reason why its use is strictly limited and not recommended (ICH class I/speci-fications 2 ppm). Carbon tetrachloride and 1,2-dichloroethane have been demonstrated to be carcinogenic in animals and potentially carcinogenic in man. 

Figure 6. Analytical plots for non-carcinogenic Class I molecules studied Acridine orange = 5.0 x lOr mol/L, DNA = 6.4 pg. = Naphthalene, JF = Anthracene, o = Phenanthrene, A = 1,2,3,4,5,6,7,8-octahydronaphthalene, + = Benzo[kjfluoran hene.

Benzo[j]fluoranthene, which only differs from benzo[k]fluoranthene by having one benzene ring in a slightly different position, has a better LOD of approximately one order of magnitude, but is a class IV carcinogen, whereas benzo[k]fluoranthene is a noncarcinogenic Class I molecule. It would also appear that benzo[j]fluoranthene is a more compact molecule, which should enhance intercalation. ... 

Permissible emissions of carcinogenic substances are divided within this guideline, into three classes of concentration in waste gas. Substances with the highest carcinogenic potential, such as benzo[a]pyrene, dibenz[a,h]anthracene and 2-naph-thylamine are listed in Class I and must not exceed a mass concentration of 0.1 mg/m in the waste gas, at a mass flow of 0.5 g/h or above. 

A slope factor is generated in the second part of the evaluation. Based on the evaluation that the chemical is a known or probable human carcinogen, a toxicity value that defines quantitatively the relationship between dose and response (i.e., the slope factor) is calculated. Slope factors are typically calculated for potential carcinogens in classes A, Bl, and B2. Quantitative estimation of slope factors for the chemicals in class C proceeds on a case-bycase basis. 

I U.S. DHHS/PHS/NTP (1998). Class S is sufficient evidence of carcinogenicity in animals. All PAHs in this table that have been evaluated are classified reasonably anticipated to be human carcinogens (RAHC). ... 

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