Toxic and Carcinogenic Chemicals

What is it that is not poison? All things are poison and nothing is without poison. It is the dose only that makes a thing not a poison. Paracelsus (1494 1541 ) Toxicity Defined
The toxicity of a substance is due to its ability to damage or disrupt the metabolism of living tissue. An acutely toxic substance can cause damage as the result of single or short-duration exposure. A chronically toxic substance causes damage after repeated or long-duration exposure or that becomes evident only after a long latency period. Carcinogens are considered a special class of chronic poisons. It is understood that essentially all chemicals, at some concentration, are toxic. This section will focus on those chemicals which can be classified as extreme toxics or severe poisons, and those which have been shown to be toxic if exposure is long-term, i.e., chronic exposures, with special attention for those that possess carcinogenic characteristics. There are special problems associated with working with these compounds, and for regulated carcinogens in particular, additional precautions are prescribed by legislation. Topics considered here include identification of the hazardous materials, proper storage and handling techniques, and legal requirements. Toxicology is the science that investigates the adverse reaction of chemicals on the biological system. The toxicity of a chemical, as defined in The Dose Makes the Poison, is related to its ability to damage an organ system, or to disrupt a biochemical process (such as the blood forming mechanism), or to disturb an enzyme system at some site in the body removed from the site of contact (as opposed to the affecting the site of contact as when a corrosive comes in contact with the skin). The systemic damage that a chemical does is not random if affects the same set of body functions in all people. The sensitivity of individuals will vary and the effect may appear worse in some persons than others, but the target function or organ does not vary.

Poison Defined: Acute versus Chronic Poisons are chemicals which cause illness, injury or death when taken in very small quantities. The legal definition of a poison is a chemical that takes less than 50 mg per kilogram of body weight to kill 50% of the victims exposed. This is really a very small amount of material about of a teaspoon for the average adult and bout 1/8 a teaspoon for a 2 year old child. There are very few chemicals that are lethal at these doses, but those that are must be classified as poisons. These materials will be classified as acute poisons because their effect is immediate. Chronic toxicity, on the other hand, refers to the systemic damage that is done after repeated exposure of low concentrations over long periods of time. Materials most often associated with chronic toxicity are those that have been labeled as carcinogens, though there are other classes of chronic toxins which must be used with equal care. All chronically toxic materials are problematic because we do not know when or if the effect of the exposure will be felt. Workers in research laboratories and in other chemicals settings should not discount any chemical exposure materials not thought to be hazardous in the recent past are often found to be carcinogenic at a later time. Most chemicals exhibit some degree of both acute toxicity and chronic toxicity. The symptoms displayed and the systemic effect will, however, differ. In addition, some materials may act as acute toxins, but show no chronic ill effects. The same is true for materials labeled as chronically toxic, which have no adverse single dose effect. Despite this lack of correlation, the effects of both forms of toxicity are definitely dose related, that is, the greater the dose, the greater the effect. Examples and more detailed discussion of acute an chronic (carcinogenic and non) toxics follows: Acute Poisons Hydrogen cyanide Hydrogen sulfide Chronic Poisons Mercury Lead Vinyl chloride Carcinogens Benzene

Carbon tetrachloride Cadmium compounds Factors that Affect Toxicity 1. Routes of exposure Toxicity varies with the route of exposure and effectiveness at which the material is absorbed. A chemical that enters the body in large quantities but is not easily absorbed is a much lower risk than one that is easily absorbed into the bloodstream. Skin contact Perhaps the most Common route of exposure is through skin contact. Fortunately the skin acts as an effective barrier against entry by most chemicals and thus greatly reduces the possibility of toxic exposure. This is not true, however, if the skin is not intact, i.e., if there is an open cut. General rule: most inorganic chemical are not easily absorbed through the skin, organic chemicals may or may not be absorbed, depending on numerous conditions. Some chemicals, such as DMSO (diethyl suffixed) greatly enhance absorption of other chemicals through the skin, so particular care should be used with the materials. Once a chemicals passes through the skin it enters the blood stream and is carried to all parts of the body. Inhalation

This is the most dangerous route of entry into body because the lungs are not an effective barrier to entry. The lung membrane allows ready passage of gases necessary to sustain life, but sadly they just as readily allow passage of chemicals that can be fatal. Chemical that pass the lung membrane are absorbed into the bloodstream and carried to all parts of the body. Absorption can be extremely rapid. The rate of absorption depends on the concentration of the toxic substance, its solubility in water, the depth of respiration and the rate of blood circulation. Ingestion

Ingestion of toxic materials is an unlikely event in the chemical laboratory as long as good hygiene practices are followed. Materials that are ingested may be absorbed

into the blood stream anywhere along the gastrointestinal tract. If the material cannot be absorbed it will be eliminated from the body. 2. Species Toxicity is species specific, with the level of sensitivity dependent upon each species. The difference in observed reaction is related to the method that each species handles the substance. The rate that the chemical is absorbed, metabolized or excreted in a greater or lesser amount, or the metabolic pathway that is utilized to handle the material will determine the end effect. Occasionally a physiological difference will determine the fate of the toxicants. For instance, some animals are not capable of vomiting so when they ingest a poison they have no means of removing the offending substance from the body. 3. Gender Though the data for human is almost nonexistent, there are definitive results that show there are gender differences in the sensitivity to certain chemicals. These differences are often not evident in the immature animals, indicating that the sensitivity is perhaps related to sex hormone production. On the other hand, there is ample evidence to show that the gender specific reproductive progress can be severely compromised by exposure to toxic substances. 4. Health Individuals that are predisposed to certain health problems, such as diseases of the liver or lungs, are more likely to be affected by exposure to toxic materials, and once exposed, more likely to experience a more severe reaction. 5. Presence of other substances Certain substances are dangerous when a person is exposed to 2 or more substances at the same time. The resulting effect is more hazardous than would be

predicted from the exposure to either of the individual substances. This is known as synergistic effect. The threshold limit value (TLV) of a chemical substance is a level to which it is believed a worker can be exposed day after day for a working lifetime without adverse health effects. Strictly speaking, TLV is a reserved term of the American Conference of Governmental Industrial Hygienists (ACGIH). However, it is sometimes loosely used to refer to other similar concepts used in occupational health and toxicology. TLVs, along with biological exposure indices (BEIs), are published annually by the ACGIH. Threshold limit value - Time weighted average (TLV-TWA): average exposure on the basis of a 8h/day, 40h/week work schedule Threshold limit value - Short-term exposure limit (TLV-STEL): spot exposure for duration of 15 minutes that cannot be repeated more than 4 times per day. STEL is expressed in parts per million (ppm), or sometimes in milligrams per cubic metre (mg/m3). Threshold limit value - Ceiling limit (TLV-C): absolute exposure limit that should not be exceeded at any time.

S.R. Bhave, IPSD, AERB