Cancer Definition

Chemical carcinogenesis is defined as the induction of neoplasms (cancerous growths) as a result of exposure to toxic substances. Carcinogenic chemicals may induce carcinomas (malignant tumors of epithelial tissue), sarcomas (malignant tumors of connective tissue) and benign tumors in humans or laboratory animals. Chemically induced cancer generally develops many years after exposure to a toxic agent. A latency period of as much as thirty years has been observed between exposure to asbestos, for example, and incidence of lung cancer. Cancer results from a series of genetic alterations that leads to the progressive disruption of the normal mechanisms controlling cellular growth. The transformation of a normal cell into a cancerous growth is a multistage process that occurs gradually over time.
There are many well-known examples of chemicals that can cause cancer in humans. The fumes of the metals cadmium, nickel, and chromium are known to cause lung cancer. Vinyl chloride has been associated with liver sarcomas. Exposure to arsenic increases the risk of skin and lung cancer. Tobacco smoking is the major cause of cancers of the lung, larynx, and bladder, and is an important cause of cancers of the pancreas and kidney. Leukemia can result from chemically induced changes in bone marrow from exposure to benzene and cyclophosphamide, among other toxicants. Other chemicals, including benzo[a]pyrene and ethylene dibromide, are considered by authoritative scientific organizations to be probably carcinogenic in humans because they are potent carcinogens in animals.


1999 Environmental Defense Fund, New York, NY 10010
Bill_Pease@edf.org

Cardiovascular or Blood Toxicity Definition


Cardiovascular and blood toxicity is defined as adverse effects on the cardiovascular or hematopoietic systems that result from exposure to chemical substances. The cardiovascular system is composed of the heart and blood vessels; the hematopoietic system is composed of various blood cell types: erythrocytes (red blood cells), leukocytes (white blood cells), and platelets. Exposure to cardiovascular toxicants can contribute to a variety of diseases, including elevated blood pressure (hypertension), hardening of the arteries (arteriosclerosis), abnormal heartbeat (cardiac arrhythmia),and decreased blood flow to the heart (coronary ischemia). Exposure to hematopoietic toxicants can reduce the oxygen carrying capacity of red blood cells, disrupt important immunological processes carried out by white blood cells, and induce cancer.
Because the cardiovascular system is complex, adverse effects resulting from exposure to chemicals can arise through a variety of mechanisms. Toxicants can contribute to cardiovascular disease by directly damaging cardiac and blood vessel tissue, initiating arteriosclerotic plaque formation, stimulating the inflammatory response, or causing kidney-related hypertension. Lead, carbon disulfide, arsenic, cadmium, ozone, and vinyl chloride have been implicated in the etiology of cardiovascular disease. These chemicals may produce functional changes, such as cardiac arrhythmias, that can have serious and often lethal consequences. They can also induce hypertension, a major cause of cardiac hypertrophy and heart failure. Several toxicants have been found to aggravate preexisting cardiovascular disease. Carbon disulfide and arsenic can irreversibly accelerate coronary heart disease.
The blood cells of the hematopoietic system can also be severely affected by chemical substances. For example, benzene, a component of motor fuel, is a hematopoietic toxin. Chronic exposure to benzene vapors leads to the decreased production of all types of blood cells (pancytopenia). The long-term effect of exposure to benzene is leukemia, a cancerous proliferation of white blood cells.

1999 Environmental Defense Fund, New York, NY 10010
Bill_Pease@edf.org

Developmental Toxicity Definition


Developmental toxicity is defined as adverse effects on the developing child that result from exposure to chemical substances. Sometimes called teratogens, developmental toxicants include agents that induce structural malformations and other birth defects, low birth weight, metabolic or biological dysfunction, and psychological or behavioral deficits that become manifest as the child grows. Developmental toxicity is often considered to be a subcategory of reproductive toxicity, but is treated as a distinct health endpoint in EDF's hazard identification system (see the separate definition of reproductive toxicity).
While developmental toxicity usually results from prenatal exposures to toxicants experienced by the mother, it can also result from paternal exposures, or from postnatal exposures experienced by a developing child. Maternal exposure to toxic chemicals during pregnancy can disrupt the development of or even cause the death of the fetus. Exposure of pregnant women to the developmental toxicant mercury, for example, has been shown to lower the birth weights of and cause severe brain damage in their children. Among the adverse effects associated with maternal exposure to toluene are central nervous system dysfunction, craniofacial and limb anomalies, and developmental delay. Dark brown pigmentation, shorter gestation time, and lower birth weight have been found in the children of women exposed to polychlorinated biphenyls (PCBs) during their pregnancies.
Paternal exposure to toxicants can cause male reproductive toxicity, such as sterility, and may contribute to early fetal loss or birth defects. For example, the occupational exposure of men to vinyl chloride has been associated with increased rates of spontaneous abortion in their wives. Early postnatal contact with toxicants (through contaminated food or air) can affect normal development. Exposure to secondhand tobacco smoke, for example, increases an infant's risk of contracting respiratory infections or succumbing to sudden infant death syndrome.

1999 Environmental Defense Fund, New York, NY 10010
Bill_Pease@edf.org

Endocrine Toxicity Definition


Endocrine toxicity is defined as adverse effects on the structure and /or functioning of the endocrine system that result from exposure to chemical substances. The endocrine system is composed of many organs and glands that secrete hormones directly into the bloodstream, including the pituitary, hypothalamus, thyroid, adrenals, pancreas, thymus, ovaries, and testes. Once synthesized, hormones are conveyed to a target tissue, where they function as chemical messengers that transmit information between cells. Hormone levels and interactions control normal physiological processes, maintaining the body's homeostasis. Because the endocrine system is complex, a toxicant may interfere at any of a number of points along a hormone's pathway of production, regulation, and action. Some chemicals may injure the glands that synthesize and secrete hormones, while others disrupt hormonal actions at the target organ. Compounds that are toxic to the endocrine system may cause diseases such as hypothyroidism, diabetes mellitus, hypoglycemia, reproductive disorders, and cancer.
A wide variety of toxic substances can disrupt the function of the endocrine system. For example, chemicals that resemble the hormone estrogen can bind to estrogen receptors located throughout the body and either mimic the natural hormone or inhibit its actions. Exposure to endocrine-disrupting chemicals such as polychlorinated biphenyls (PCBs) and DDT have caused a host of toxic effects in wildlife, including impaired reproduction and development. Other endocrine toxicants, such as persistent organochlorine pesticides and dioxins, are being studied for their possible role in promoting hormone- induced cancers (such as breast cancer) and in lowering sperm counts and male fertility.
Specific organs and glands in the endocrine system are known to be damaged by chemical toxicants. Several chemicals and drugs can be toxic to the cells of the pancreas that produce insulin. Exposure to the rodenticide Vacor (N-3-pyridylmethyl-N'-p-nitrophenyl urea) can interfere with the secretion and function of pancreatic hormones, resulting in diabetes mellitus and hyperglycemia. Polyhydroxyphenols and the therapeutic drug lithium can disrupt thyroid gland function and cause hypothyroidism and goiter. Endocrine and reproductive dysfunction have been reported in men exposed to inorganic lead. Chronic exposure to lead can cause direct testicular toxicity, followed by hypothalamic or pituitary gland disturbances.

1999 Environmental Defense Fund, New York, NY 10010
Bill_Pease@edf.org

Gastrointestinal or Liver Toxicity Definitions

Gastrointestinal and liver toxicity is defined as adverse effects on the structure and/or functioning of the gastrointestinal tract, liver, or gall bladder that result from exposure to chemical substances. The liver functions as a center for metabolism, processing chemicals we are exposed to so they can be utilized, detoxified, or excreted. While chemicals absorbed from the gastrointestinal tract are always processed by the liver, toxicants that enter the body through other routes of exposure can also reach the liver via its blood supply from the hepatic artery and the portal vein. The liver is frequently subject to injury induced by chemicals, called hepatotoxins, because of its role as the body's principal site of metabolism.

Necrosis, or liver cell death, is a common effect of acute exposure to hepatotoxic chemicals like beryllium, phosphorus, and urethane. The necrosis can be localized in specific areas of the liver or be more widespread. The liver is usually able to recover from necrosis because of its remarkable regenerative capacity. Exposure to hepatotoxic substances can also cause fatty liver (steatosis), hepatitis, jaundice, cholestasis, chronic liver damage (cirrhosis), and cancer. Carbon tetrachloride and related chemicals, such as chloroform, are linked to steatosis, necrosis, and cirrhosis of the liver. The most frequent cause of cirrhosis, however, is the habitual consumption of large quantities of alcohol. Cancer of the liver has been associated with occupational exposures to arsenic, copper, and vinyl chloride.
The gastrointestinal, or digestive, tract is composed of the esophagus, stomach, pancreas, and small and large intestines. The gastrointestinal tract is the site of entry for chemicals that are ingested. Exposure to chemicals that are toxic to the digestive tract can cause anorexia, nausea, vomiting, abdominal cramps, and diarrhea. There are four major types of tissue response to gastrointestinal injury from toxic agents: ulceration, necrosis, inflammation, and proliferation, including cancer. Some chemicals that cause gastrointestinal injury are halogenated aromatic hydrocarbons, including chlorobenzene and hexachlorobenzene, and such metals as lead, mercury, arsenic, and cadmium. Nitrosamines have been shown to cause colon cancer in humans.

1999 Environmental Defense Fund, New York, NY 10010
Bill_Pease@edf.org

Immunotoxicity Definitions


Immunotoxicity is defined as adverse effects on the functioning of the immune system that result from exposure to chemical substances. Altered immune function may lead to the increased incidence or severity of infectious diseases or cancer, since the immune system's ability to respond adequately to invading agents is suppressed. Identifying immunotoxicants is difficult because chemicals can cause a wide variety of complicated effects on immune function. Observations in humans and studies in rodents have clearly demonstrated that a number of environmental and industrial chemicals can adversely affect the immune system. Exposure to asbestos, benzene, and halogenated aromatic hydrocarbons such as polybrominated biphenyls (PBBs), polychlorinated biphenyls (PCBs), and dioxins (TCDD) can lead to immunosuppression in humans. Toxic agents can also cause autoimmune diseases, in which healthy tissue is attacked by an immune system that fails to differentiate self-antigens from foreign antigens. For example, the pesticide dieldrin induces an autoimmune response against red blood cells, resulting in hemolytic anemia.
Also considered to be immunotoxicants, allergens are compounds that stimulate the immune system and can cause hypersensitivity reactions or allergies. Many chemicals induce allergic reactions in humans and experimental animals, producing a variety of clinical manifestations, such as asthma, rhinitis, and anaphylaxis. The industrial chemical toluene diisocyanate (TDI) and metals such as nickel and beryllium are notable examples of allergenic agents.

1999 Environmental Defense Fund, New York, NY 10010
Bill_Pease@edf.org

Kidney Toxicity Definition


Nephrotoxicity is defined as adverse effects on the kidney, ureter, or bladder that result from exposure to chemical substances. The kidney not only is the major excretory organ in the body, but also performs nonexcretory functions, such as regulating blood pressure and blood volume. Since the kidneys receive approximately 25 percent of cardiac output, any chemical in systemic circulation is delivered to them in relatively high amounts. This makes the kidney unusually susceptible to the toxic effects of chemicals. Some nephrotoxic agents cause acute injury to the kidney, while others produce chronic changes that can lead to end-stage renal failure or cancer. The consequences of renal failure can be profound, sometimes resulting in permanent damage that requires dialysis or kidney transplantation.

1999 Environmental Defense Fund, New York, NY 10010
Bill_Pease@edf.org