considers reproductive toxins, and additional information can be found through the NLM TOXNET system. The study of reproductive toxins is an active area of research, and laboratory personnel should consult resources that are updated regularly for information.
4.C.3.5 Toxins Affecting Other Target Organs
Target organs outside the reproductive and neurological systems are also affected by toxic substances in the laboratory. Most of the chlorinated hydrocarbons, benzene, other aromatic hydrocarbons, some metals, carbon monoxide, and cyanides, among others, produce one or more effects in target organs. Such an effect may be the most probable result of exposure to the particular chemical. Although this chapter does not include specific sections on liver, kidney, lung, or blood toxins, many of the LCSSs mention those effects in the toxicology section.
A carcinogen is a substance capable of causing cancer. Cancer, in the simplest sense, is the uncontrolled growth of cells and can occur in any organ. The mechanism by which cancer develops is not well understood, but the current thinking is that some chemicals interact directly with DNA, the genetic material in all cells, to result in permanent alterations. Other chemical carcinogens modify DNA indirectly by changing the way cells grow. Carcinogens are chronically toxic substances; that is, they cause damage after repeated or long-duration exposure, and their effects may become evident only after a long latency period. Carcinogens are particularly insidious toxins because they may have no immediate apparent harmful effects.
Because cancer is a widespread cause of human mortality, and because exposure to chemicals may play a significant role in the onset of cancer, a great deal of attention has been focused on evaluation of the carcinogenic potential of chemicals. However, a vast majority of substances involved in research, especially in laboratories concerned primarily with the synthesis of novel compounds, have not been tested for carcinogenicity. Compounds that are known to pose the greatest carcinogenic hazard are referred to as select carcinogens, and they constitute another category of substances that must be handled as PHSs according to the OSHA Laboratory Standard. A select carcinogen is defined in the OSHA Laboratory Standard as a substance that meets one of the following criteria:
1. It is regulated by OSHA as a carcinogen.
2. It is listed as known to be a carcinogen in the latest Annual Report on Carcinogens issued by the National Toxicology Program (NTP) (HHS/CDC/NTP, 2005).
3. It is listed under Group 1 (carcinogenic to humans) by the International Agency for Research on Cancer (IARC).
4. It is listed under IARC Group 2A (probably carcinogenic to humans) or 2B (possibly carcinogenic to humans), or under the category “reasonably anticipated to be a carcinogen by the NTP,” and causes statistically significant tumor incidence in experimental animals in accordance with any of the following criteria: (a) after inhalation exposure of 6 to 7 hours per day, 5 days per week, for a significant portion of a lifetime to dosages of less than 10 mg/m3; (b) after repeated skin application of less than 300 mg/kg of body weight per week; or (c) after oral dosages of less than 50 mg/kg of body weight per day.
Chemicals that meet the criteria of a select carcinogen are classified as PHSs and should be handled using the basic prudent practices given in Chapter 6, section 6.C, supplemented by the additional special practices outlined in Chapter 6, section 6.D. Work with compounds that are possible human carcinogens may or may not require the additional precautions given in section 6.D. For these compounds, the LCSS should indicate whether the substance meets the additional criteria listed in category 4 and must therefore be treated as a select carcinogen. If an LCSS is not available, consultation with a safety professional such as a CHO may be necessary to determine whether a substance should be classified as PHS. Lists of known human carcinogens and compounds that are “reasonably anticipated to be carcinogens” based on animal tests can be found in the 11th Report on Carcinogens (HHS/CDC/NTP, 2005). This report is updated periodically. Check the NTP Web site (ntp.niehs.nih.gov) for the most recent edition. Additional information can be found on the OSHA and IARC Web sites (www.osha.gov and www.iarc.fr).
In the laboratory many chemical substances are encountered for which there is no animal test or human epidemiological data on carcinogenicity. In these cases, trained laboratory personnel must evaluate the potential risk that the chemical in question is a carcinogenic substance. This determination is sometimes made on the basis of knowledge of the specific classes of compounds and functional group types that have previously been correlated with carcinogenic activity. For example, chloromethyl methyl ether is a known human carcinogen and therefore is regarded as an OSHA select carcinogen requiring the handling procedures outlined in section 6.D. On the other hand, the carcinogenicity of ethyl chloromethyl ether and certain other alkyl chloromethyl ethers is not established, and