Evidence is sufficient to conclude that there is a causal association between exposure to a specific agent and a specific health outcome in humans. The evidence is supported by experimental data and fulfills the guidelines for sufficient evidence of an association (below). The evidence must be biologically plausible and satisfy several of the guidelines used to assess causality, such as: strength of association, dose-response relationship, consistency of association, and a temporal relationship.

• Benzene and

  • acute leukemia

  • aplastic anemia

• Sarin and a dose-dependent acute cholinergic syndrome that is evident seconds to hours subsequent to sarin exposure and resolves in days to months

Evidence is sufficient to conclude that there is a positive association. That is, a consistent positive association has been observed between exposure to a specific agent and a specific health outcome in human studies in which chance and bias, including confounding, could be ruled out with reasonable confidence. For example, several high-quality studies report consistent positive associations, and the studies are sufficiently free of bias, including adequate control for confounding.

• Benzene and adult leukemia

• Solvents and acute leukemia

• Propylene glycol and allergic contact dermatitis

• Pyridostigmine bromide and transient acute cholinergic effects in doses normally used in treatment and for diagnostic purposes

• Anthrax vaccination and transient acute local and systemic effects

• Botulinum toxoid vaccination and transient acute local and systemic effects

Evidence is suggestive of an association between exposure to a specific agent and a specific health outcome, but the body of evidence is limited by the inability to rule out chance and bias, including confounding, with confidence. For example, at least one high-quality study reports a positive association that is sufficiently free of bias, including adequate control for confounding. Other corroborating studies provide support for the association, but they were not sufficiently free of bias, including confounding. Alternatively, several studies of lower quality show consistent positive associations, and the results are probably not due to bias, including confounding.

• Tetrachloroethylene and dry-cleaning solvents and

  • bladder cancer

  • kidney cancer

  • organophosphorus insecticides and

  • non-Hodgkin’s lymphoma

  • adult leukemia

  • adult leukemia

• Solvents and

  • adult leukemia

  • myelodysplastic syndromes

  • bladder cancer

  • multiple myeloma

• Carbamates and non-Hodgkin’s lymphoma

• Benzene and non-Hodgkin’s lymphoma

• organophosphorus insecticide exposure with OP poisoning and long-term neurobehavioral effects (that is, abnormal results on neurobehavioral test batteries and symptom findings)

• Solvents and neurobehavioral effects (that is, abnormal results on neurobehavioral test batteries and symptom findings)

• Solvents and

  • hepatic steatosis

  • chronic glomerulonephritis

  • reactive airways dysfunction syndrome (RADS) which would be evident with exposure and could persist for months or years

• Insecticides and allergic contact dermatitis

• Sarin at doses sufficient to cause acute cholinergic signs and symptoms and subsequent long-term health effects

Evidence is of insufficient quantity, quality, or consistency to permit a conclusion regarding the existence of an association between exposure to a specific agent and a specific health outcome in humans.

• Solvents and

  • oral, nasal, or laryngeal cancer

  • stomach, rectal, or pancreatic cancer

  • bone cancer

  • melanoma or nonmelanoma skin cancer

  • ovarian or uterine cancer

  • prostate cancer

• Solvents other than trichloroethylene and cervical cancer

• Solvents other than tetrachloroethylene and dry-cleaning solvents and

  • esophageal cancer

  • bladder cancer

  • lung cancer

• Specific solvents other than benzene and

  • brain and other central nervous system cancers

  • non-Hodgkin’s lymphoma

  • acute and adult leukemia

• Solvents other than trichloroethylene and mixtures of benzene, toluene, and xylene and colon cancer

• Benzene and myelodysplastic syndromes

• Insecticides and

  • lung cancer

  • pancreatic cancer

  • soft tissue sarcomas

  • prostate, testicular, or bladder cancers

  • kidney cancers

  • brain and other central nervous system cancers

• Insecticides and solvents

  • Hodgkin’s disease

  • hepatobiliary cancers

  • multiple myeloma

• Lindane and solvents and breast cancer

• Parental preconception exposure to insecticides and childhood leukemias, brain and other central nervous system cancers, and non-Hodgkin’s lymphoma

• Parental preconception exposure to solvents and neuroblastoma and childhood brain cancers

• Uranium and

  • lymphatic cancer

  • bone cancer

• Insecticides and solvents and

  • peripheral neuropathy

  • Parkinson’s disease

  • amyotrophic lateral sclerosis

  • Alzheimer’s disease

• Solvents and

  • multiple sclerosis

  • a long-term reduction in color discrimination

  • long-term hearing loss

  • long-term reduction in olfactory function

• Uranium and nervous system disease

• Insecticides and solvents and male or female infertility after cessation of exposure

• Parental preconception exposure to insecticides or solvents and

  • spontaneous abortion or other adverse pregnancy outcomes

  • congenital malformations

• Uranium and reproductive or developmental dysfunction

• Insecticides and aplastic anemia

• Solvents other than benzene and aplastic anemia

• Insecticides and solvents and

• irreversible cardiovascular outcomes

• persistent respiratory symptoms or impairment after cessation of exposure

• Solvents and

• cirrhosis

• alterations in liver function tests after cessation of exposure

• chronic pancreatitis and other persistent gastrointestinal outcomes

• the systemic rheumatic diseases: scleroderma, rheumatoid arthritis, undifferentiated connective tissue disorders, and systemic lupus erythematosus

• Exposure to uranium and lung cancer at higher levels of cumulative exposure (>200 mSv or 25 cGy)

• Uranium and

• nonmalignant respiratory disease

• gastrointestinal disease

• immune-mediated disease

• effects on hematological parameters

• genotoxic effects

• cardiovascular effects

• hepatic disease

• dermal effects

• ocular effects

• musculoskeletal effects

• Pyridostigmine bromide and long-term adverse health effects

• Exposure to sarin at low doses insufficient to cause acute cholinergic signs and symptoms and subsequent long-term adverse health effects

• Anthrax vaccination and long-term adverse health effects

• Botulinum toxoid vaccination and long-term adverse health effects

• Multiple vaccinations and long-term adverse health effects

Evidence is consistent in not showing a positive association between exposure to a specific agent and a specific health outcome after exposure of any magnitude. A conclusion of no association is inevitably limited to the conditions, magnitudes of exposure, and length of observation in the available studies. The possibility of a very small increase in risk after exposure studied cannot be excluded.

• Exposure to uranium and lung cancer at cumulative internal dose levels lower than 200 mSv or 25 cGy

• Uranium and clinically significant renal dysfunction

• Tetrachloroethylene and dry-cleaning solvents and esophageal cancer

• Trichloroethylene and colon cancer

• Mixtures of benzene, toluene, and xylene and colon cancer

• Tetrachloroethylene and dry-cleaning solvents and lung cancer

• Trichloroethylene and cervical cancer

• Solvents and kidney cancer

• Benzene and solvents and brain and other central nervous system cancers

• Parental preconception exposure to solvents and childhood leukemia

• Organophosphorous insecticide exposure without OP poisoning and long-term neurobehavioral effects (that is, abnormal results on neurobehavioral test batteries and symptom findings)