Labeling Carcinogens

When there is generally accepted, well-established evidence that a chemical is known to cause cancer in humans, it should be labeled with the following statements of hazard or equivalent  

OVEREXPOSURE MAY CREATE CANCER RISK CANCER SUSPECT AGENT (as required by Government Regulation) 

CANCER HAZARD BASED ON TESTS WITH LABORATORY ANIMALS OVEREXPOSURE MAY CREATE CANCER RISK 

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Daniel PM, Pratt OE, Prichard MML. 1967. Metabolism of labelled carcinogenic hydrocarbons in rats. Nature 215 1142-1146. 

DETERMINATION OF SOIL ADSORPTION PARTITION COEFFICIENTS OF C-LABELED CARCINOGENIC ORGANIC CHEMICALS BY LIQUID SCINTILLATION... 

Free acrylamide content Aciylamide monomer is labeled carcinogenic (R45 risk phrase). There must be less than 100 ppm in the polymer powder. Method high pressure liquid chromatography. 

The standard shipping symbols (see Section App. 3.4) are customarily used by most chemical manufacturers to identify the hazards of their products. In the United States these symbols are not mandated by any regulations although the specific hazard(s) of each substance must be identified (see Chapter 18). There are particular requirements for labeling carcinogenic materials and for identifying laboratories where carcinogens are handled and stored. 

PROT—with the exception of the aromatic process oils, which are labeled carcinogenic (worldwide) and the three diesters, which are currently classified as potential carcinogens (North America), compounders have little to be concerned with the impact of the plasticizer products discussed in this chapter on the environment. 

Toxicity. Antimony has been found not to be a carcinogen or to present any undue risk to the environment (9). However, because antimony compounds also contain minor amounts of arsenic which is a poison and a carcinogen, warning labels are placed on all packages of antimony trioxide. 

On the basis of these differences in species response it was concluded that phthalates do not pose a significant health hazard to humans. This view is home out by the EU Commission decision of July 25, 1990 which states that DEHP shall not be classified or labeled as a carcinogenic or an irritant substance (42). This has been reaffirmed in a comprehensive review (43) which concludes that "peroxisome proliferators constitute a discrete class of nongenotoxic rodent hepatocarcinogens and that the relevance of thek hepatocarcinogenic effects for human hazard assessment is considered to be negligible."... 

The experiments with deuterium-labeled nitrosamines illustrate two important points. One is that oxidation of nitrosamines takes place at more than one position in the molecule, and the outcome of the balance of such competing reactions probably is the determinant of carcinogenic potency. The second is that the reason for the failure of carcinogenesis to be mirrored in many cases by the microsomally activated bacterial mutagenicity is that there can be several metabolic steps leading to formation of the proximate carcinogenic agent and not all of these need necessarily involve microsomal enzymes. ... 

In a study for precursor determination, we stem-fed individual Burley leaves with nicotine-2 - C or nornicotine-2 - C (29). Subsequently, the leaves were air cured, dried and analyzed for NNN and NNN- C. Recovery of the p-activity in the form of NNN- C amounted to 0.009% and 0.007%, respectively of the stem-fed label. This demonstrates that both alkaloids give rise to NNN. More importantly, it points to the fact that the tertiary amine, nicotine, which constitutes 0.5-2.6% of commercial tobaccos (26,27), is the major precursor for the carcinogenic tobacco-specific NNN, while the secondary amine, nornicotine is of lesser importance because it amounts to only 0.005-0.06% in tobacco (Figure 8). 

Drug Studies in Pediatric Patients Medical Officer s Review Statistical Review Evaluation Chemistry, Manufacturing and Controls CDER Labeling and Nomenclature Committee Clinical Pharmacology/Biopharmaceutics Microbiologist s Review Pharmacokinetics Review Carcinogenicity Assessment... 

Toxic (T) Chronic NOEC < 0.01 mg/1 for fresh or marine water organisms, Category 1 or 2 carcinogen or mutagen or Category 1, 2 or 3 toxic for reproduction or chronically toxic (i.e., labelled with T or harmful (Xn) with R48) Not applicable... 

The carcinogenic properties of aromatic oils have resulted in a search for alternative products for the tyre and rubber industries. BP offers a series of non-labelled alternatives, known as the VivaTec range, manufactured to standards laid down by BLIC, the body that represents the interests of rubber organisations in Europe. 

Preparations containing >0,5% lead chromate are required to be labelled according to EU Guideline 67/548/EEC (Annex I) as toxic (Symbol skull and crossbones) and beside others with the Risk phrases R 40 (limited evidence of carcinogenic effect), R 61 (may cause harm to the unborn child) and R 62 (possible risk of impaired fertility). 

But we are moving too quickly. Before we can begin to contemplate the contribution of all these environmental carcinogens to the total cancer problem we need to acquire a better understanding of what is meant by the terms carcinogen or cancer-causing chemical and of how certain substances get to carry these labels. 

Now, finally, the significance of all this. Because, as a practical matter, it is difficult to conduct bioassays with more than 100-150 animals per dose level (usually split evenly between males and females), it can be seen from the above table that in the best of circumstances, with a zero or very low incidence outcome in control animals, it would be necessary for a tested compound to induce something like an 8-15% tumor incidence before we could fairly label it a carcinogen. This is a fairly large risk, yet our typical cancer bioassay has what might be called a limit of detection at about this level. Like chemical assays, bioassays are limited in their ability to detect effects - in this case, the carcinogenicity of a chemical substance. 

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