Primary carcinogens

For certain carcinogenic primary N-hydroxy arylamines, metabolic... 

Operations/processes carcinogen Primary body organ where encountered Affected... 

Genotoxicity/mutagenicity, carcinogenicity, primary irritation, and skin sensitization are the most well-covered toxicological endpoints as standardized assays for their assessment were established several years ago. There are various databases of such data that can be freely accessed via the internet and a selection of these is listed here (also see Chapters 5 and 6) ... 

Genotoxic carcinogens Primary, direct acting Alkylating agents Dimethylsulphate... 

Propylene oxide is a primary irritant, a mild protoplasmic poison, and a mild depressant of the central nervous system. Skin contact, even in dilute solution (1%), may cause irritation to the eyes, respiratory tract, and lungs. Propylene oxide is a suspected carcinogen in animals. The LC q (lowest lethal concentration by inhalation in tats) is 4000 mg/kg body weight. The LD q (oral) is 930 mg/kg. The LD q (dermal) is 1500 mg/kg. The TWA (8-h exposure) is 100 ppm and the STEP (15-min exposure) is 150 ppm. 

Nitrosamines. Findings that secondary amines, so common in mbber accelerators, can react with NO species to form the suspected human carcinogens, nitrosamines, have prompted active programs to develop alternative accelerators. Neither primary nor tertiary amines form stable nitrosamines and they are generally considered to be safe materials. The abiHty of each type of common mbber accelerator class to form nitrosamines has been summarized and depends on their 1°, 2°, or 3° nature (30). 

Direct dyes are defined as anionic dyes substantive to ceUulosic fibers (cotton, viscose, etc), when applied from an aqueous bath containing an electrolyte. Before the discovery of Congo Red in 1884, only mordanted cotton could be dyed. Congo Red [573-58-0] (62) (Cl Direct Red 28 Cl 22120) a primary symmetrical disazo dye, which is made readily from bisdiazotized benzidine and naphthionic acid [84-86-6] (4-arnino-l-naphthalenesulfonic acid), was the precursor of a most important line of dyes, including all shades, derived from benzidine and its homologues. Today, no benzidine dye is produced because benzidine is carcinogenic. 

Neither the mechanism by which benzene damages bone marrow nor its role in the leukemia process are well understood. It is generally beheved that the toxic factor(s) is a metaboHte of benzene (107). Benzene is oxidized in the fiver to phenol [108-95-2] as the primary metabolite with hydroquinone [123-31-9] catechol [120-80-9] muconic acid [505-70-4] and 1,2,4-trihydroxybenzene [533-73-3] as significant secondary metabolites (108). Although the identity of the actual toxic metabolite or combination of metabolites responsible for the hematological abnormalities is not known, evidence suggests that benzene oxide, hydroquinone, benzoquinone, or muconic acid derivatives are possibly the ultimate carcinogenic species (96,103,107—112). 

Cobalt compounds can be classified as relatively nontoxic (33). There have been few health problems associated with workplace exposure to cobalt. The primary workplace problems from cobalt exposure are fibrosis, also known as hard metal disease (34,35), asthma, and dermatitis (36). Finely powdered cobalt can cause siUcosis. There is Htfle evidence to suggest that cobalt is a carcinogen in animals and no epidemiological evidence of carcinogenesis in humans. The LD q (rat) for cobalt powder is 1500 mg/kg. The oral LD q (rat) for cobalt(II) acetate, chloride, nitrate, oxide, and sulfate are 194, 133, 198, 1700, 5000, and 279 mg/kg, respectively the intraperitoneal LD q (rat) for cobalt(III) oxide is 5000 mg/kg (37). 

CYP1B1 (chromosome 5) has been linked to primary congenital glaucoma. CYP1B1 is not regularly expressed in liver but is often found in various kinds of tumours. It metabolizes retinoids and many aromatic amines and PAHs to potentially carcinogenic products. 

Although ultra accelerators or sulfur donors can be used together with primary accelerator (such as sulfenamide, TBBS) to improve cure rate as well as the heat resistance [16-18], their use is restricted because of the associated nitrosamine issue [19]. Accelerators derived from secondary amines, for example, MBS, TMTD, TETD, TMTM, and OTOS fall into this category. The combination of sulfenamide, such as CBS or TBBS, and a thiuram, such as TMTD or TETD, shows high-cure rates but suffers from the adverse effects on scorch resistance and vulcanizate dynamic property [20]. Additionally as previously mentioned, the use of TMTD or Tetraethylthiuram disulhde (TETD) or A-oxidiethylene dithiocarbamyl-A -oxidiethylene sulfenamide (OTOS) or 4,4 -Dithiodimorpholine (DTDM) is undesirable [21] due to concerns over carcinogenic nature of the A-nitrosamines formed from the parent amines. The solution to this originated by introduction of nitrosamine safe ultra accelerator such as TBzTD [22,23]. 

The Ames test involves the reversion from a his— to his+ phenotype in any one of multiple bacterial strains (usually five strains are tested simultaneously). If the addition of test compound to a his— strain of bacteria allows them to grow on histidine deficient media, the obvious conclusion is compound-induced mutagenesis and a high potential hazard for the compound being carcinogenic. This test can also be conducted in the presence or absence of metabolic activation, in order to provide more information on potential risks (i.e., the parent compound may not be mutagenic, but the primary metabolite may present a safety risk). In practice, a positive Ames test almost always leads to discontinuing work on a compound of interest, and so these data are always collected prior to nomination of a compound for development. 

O Exposure to ultraviolet radiation from the sun is recognized as one of the primary triggers for skin carcinogenesis. Based on their wavelengths, UV radiation is divided into three components UVA (320 00 nm), UVB (280-320 nm), and UVC (200-280 nm).15 UVB accounts for only 5% of the solar radiation that reaches the earth, but it is the primary carcinogenic component in the UV spectrum.15 The following sequence of events describes the process in which UV radiation causes skin cancer (1) UV radiation reaches the earth, and on the skin, it reaches the cells in the epidermal layer (i.e., squamous cells, basal cells, and melanocytes),16 (2) the UV radiation (specifically... 

Other factors associated with the risk of NMSC include exposure to ionizing radiation and arsenic, which is connected with BCC. Chemical carcinogens that give rise to NMSC include industrial hydrocarbons that are found in coal tars, soot, asphalt, paraffin waxes, and tobacco.21 Exposure to the human papilloma virus (HPV-6, -11, -16, and -18) has been linked to SCC.31 Lastly, a personal history of previous melanoma is a risk factor for developing another primary melanoma. 

Pienta RJ, Poiley JA, Lebherz WB III. 1977. Morphological transformation of early-passage golden Syrian hamster embryo cells derived from cryopreserved primary cultures as a reliable in vitro bioassay for identifying diverse carcinogens. Int J Cancer 19 642-655. 

Probst GS, Hill LE. 1985. Tests for the induction of DNA repair synthesis in primary cultures of adult rat hepatocytes. In Ashby J, de Serres FJ, et al., eds. Progress in mutation research. Vol. 5. Evaluation of short-term tests for carcinogens. Amsterdam, The Netherlands. Elsevier Science Publishers, 381-386. 

Primary Arylamines, and N-Methyl Arylamines. Putative ultimate carcinogenic metabolites are designated I-XIII. Ac, acetyl Gl, glucuronyl. 

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