Chemical mixtures: challenge for toxicology and risk assessment.

It is now well-recognized that human environmental exposures are not to single chemicals. Rather, humans are exposed, either concurrently or sequentially, to multiple chemicals. Challenges that chemical mixtures pose for risk assessment and toxicology are presented. Challenge areas include increasing the peer-reviewed publication of human studies, improving access to peer-reviewed data and examining multiple target organs. Two difficult challenges are development of a common, consistent language and the use of appropriate and innovative experimental designs and analyses. The challenge of elucidation of mechanism(s) offers a rational basis for extrapolation across dose levels, exposure durations and exposure routes as well as to other species and to other similar chemicals. Of particular importance is focusing effort on those areas of investigation where answers have the greatest potential for reducing uncertainty in risk assessments for chemical mixtures and on those chemical mixtures and multiple chemical exposures that have the greatest potential impact on human health. A particularly fruitful area for future investigation is determination of the likelihood of nonadditive interactions in humans exposed to multiple chemicals at environmental exposure levels.

[1]  P K Gessner,et al.  Isobolographic analysis of interactions: an update on applications and utility. , 1995, Toxicology.

[2]  E. Berman,et al.  Lethality and hepatotoxicity of complex waste mixtures. , 1988, Environmental research.

[3]  Andrew J. McMichael,et al.  Complex mixtures and cancer risk. , 1990, IARC scientific publications.

[4]  I. Sipes,et al.  Modulation of chemical-induced lung and liver toxicity by all-trans-retinol in the male Sprague-Dawley rat. , 1995, Toxicology.

[5]  E. Berman,et al.  Evaluation of the nephrotoxicity of complex mixtures containing organics and metals: advantages and disadvantages of the use of real-world complex mixtures. , 1995, Environmental health perspectives.

[6]  Division on Earth.  Risk Assessment in the Federal Government: Managing the Process , 1983 .

[7]  E. Hodgson.  A textbook of modern toxicology , 1987 .

[8]  D. DeMarini,et al.  Use of the microscreen phage‐induction assay to assess the genotoxicity of 14 hazardous industrial wastes , 1988, Environmental and molecular mutagenesis.

[9]  Edward J. Calabrese.  Multiple Chemical Interactions , 1990 .

[10]  V J Feron,et al.  Toxicology of chemical mixtures: challenges for today and the future. , 1995, Toxicology.

[11]  B. L. Johnson,et al.  Chemical mixtures released from hazardous waste sites: implications for health risk assessment. , 1995, Toxicology.

[12]  L K Teuschler,et al.  Current and future risk assessment guidelines, policy, and methods development for chemical mixtures. , 1995, Toxicology.

[13]  Jane Ellen Simmons,et al.  14 – Nephrotoxicity Resulting from Multiple Chemical Exposures and Chemical Interactions , 1994 .

[14]  Raymond S. H. Yang.  1 – Introduction to the Toxicology of Chemical Mixtures , 1994 .

[15]  J. E. Simmons,et al.  Toxicological evaluation of complex industrial wastes: implications for exposure assessment. , 1989, Toxicology letters.

[16]  E J Calabrese,et al.  Toxicological consequences of multiple chemical interactions: a primer. , 1995, Toxicology.

[17]  Curtis D. Klaassen,et al.  Casarett and Doull's Toxicology. The Basic Science of Poisons , 1981 .

[18]  Daniel Krewski,et al.  Statistics in Toxicology. , 1994 .

[19]  E. Berman,et al.  Toxicity of complex waste mixtures: a comparison of observed and predicted lethality. , 1989, Journal of toxicology and environmental health.

[20]  Raymond S. H. Yang.  Toxicology of chemical mixtures : case studies, mechanisms, and novel approaches , 1994 .

[21]  D. Svendsgaard,et al.  Toxicology studies of a chemical mixture of 25 groundwater contaminants: hepatic and renal assessment, response to carbon tetrachloride challenge, and influence of treatment-induced water restriction. , 1994, Journal of toxicology and environmental health.

[22]  E. Silbergeld,et al.  Health effects studies of exposure from hazardous waste sites--where are we today? , 1985, American journal of industrial medicine.

[23]  M. F. Ackermann,et al.  Toxicology studies of a chemical mixture of 25 groundwater contaminants. II. Immunosuppression in B6C3F1 mice. , 1989, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[24]  R. Levine,et al.  Public health investigations of hazardous organic chemical waste disposal in the United States. , 1985, Environmental health perspectives.

[25]  V. Feron,et al.  Safety evaluation of the mixture of chemicals at a specific workplace: theoretical considerations and a suggested two-step procedure. , 1995, Toxicology letters.

[26]  G. Plaa,et al.  1 – Factors to Consider in the Design and Evaluation of Chemical Interaction Studies in Laboratory Animals , 1990 .

[27]  G. Boorman,et al.  Residual damage to hematopoietic system in mice exposed to a mixture of groundwater contaminants. , 1991, Toxicology letters.

[28]  H. Abadin,et al.  Toxicological profile for chlordane , 1994 .

[29]  R E Chapin,et al.  Toxicology studies of a chemical mixture of 25 groundwater contaminants. III. Male reproduction study in B6C3F1 mice. , 1989, Fundamental and applied toxicology : official journal of the Society of Toxicology.