Toxic interactions among environmental pollutants: corroborating laboratory observations with human experience.

Combined exposures to multiple chemicals may result in interactions leading to a significant increase or decrease in the overall toxicity of the mixture compared to the summation of the toxicity of the components. A large number of chemical interactions have been described in animal studies by administering high doses of chemicals by routes and scenarios often different from anticipated human exposures. Though limited, there is some evidence for the occurrence of several supra-additive (the combined effects are greater than the simple summation of the individual effects) and infra-additive (the combined effects are smaller than the simple summation of the individual effects) chemical interactions in humans. For example, toxicokinetic interactions between several solvents have been found to occur in the workplace, whereas those involving pesticides have been reported less frequently, especially during accidental exposures. Toxic interactions involving nutritionally important metals and metalloids appear to occur more frequently, since several of them have an important role in a variety of physiological and biochemical processes. On the contrary, there is not much evidence to confirm the occurrence of toxic interactions among the commonly encountered inorganic gaseous pollutants in humans. Overall, the majority of chemical interactions observed in animal studies have neither been investigated in humans nor been extrapolated to humans based on appropriate mechanistic considerations. Future research efforts in the chemical interactions arena should address these issues by focusing on the development of mechanistically and biologically based models that allow predictions of the extent of interactions likely to be observed in humans.

[1]  Combined effect of ozone and sulfuric acid on pulmonary function in man. , 1987, American Industrial Hygiene Association journal.

[2]  R. Menke,et al.  The relationship of ingested iron to the absorption of mercuric oxide. , 1984, The American journal of emergency medicine.

[3]  A. R. Byrne,et al.  Correlation between selenium and mercury in man following exposure to inorganic mercury , 1975, Nature.

[4]  G. Mulder,et al.  Use of pentachlorophenol as long-term inhibitor of sulfation of phenols and hydroxamic acids in the rat in vivo. , 1983, Biochemical pharmacology.

[5]  D. House,et al.  A survey of effects of gaseous and aerosol pollutants on pulmonary function of normal males. , 1983, Archives of environmental health.

[6]  J. Deng,et al.  Outbreak of carbon tetrachloride poisoning in a color printing factory related to the use of isopropyl alcohol and an air conditioning system in Taiwan. , 1987, American journal of industrial medicine.

[7]  H. Ragan Effects of iron deficiency on the absorption and distribution of lead and cadmium in rats. , 1977, The Journal of laboratory and clinical medicine.

[8]  M. Ikeda,et al.  Mutual metabolic suppression between benzene and toluene in man , 1988, International archives of occupational and environmental health.

[9]  D. Pashley,et al.  Acute fluoride toxicity: the influence of acid-base status. , 1978, Toxicology and applied pharmacology.

[10]  G. W. Pearce,et al.  Pesticides Formulation, Relation to Safety in Use , 1953 .

[11]  R. Frank SO2-particulate interactions: recent observations. , 1980, American journal of industrial medicine.

[12]  R. Goyer,et al.  The influence of iron deficiency on tissue content and toxicity of ingested lead in the rat. , 1972, The Journal of laboratory and clinical medicine.

[13]  M. Andersen,et al.  Physiologically based pharmacokinetic analyses of simple mixtures. , 1994, Environmental health perspectives.

[14]  O. Fitzhugh,et al.  Marked potentiation in mammalian toxicity from simultaneous administration of two anticholinesterase compounds. , 1957, The Journal of pharmacology and experimental therapeutics.

[15]  H. Altenkirch [Sniffing addiction: chronic solvent abuse with neurotoxic effects in children and juveniles (author's transl)]. , 1979, Deutsche medizinische Wochenschrift.

[16]  Occupational health and safety in Finland. , 1983, Scandinavian journal of work, environment & health.

[17]  H. Mehendale Mechanism of the lethal interaction of chlordecone and CCl4 at non-toxic doses. , 1989, Toxicology letters.

[18]  S. D. Murphy,et al.  A simplified bioassay for organophosphate detoxification and interactions. , 1974, Toxicology and applied pharmacology.

[19]  J. Barton,et al.  Effects of iron on the absorption and retention of lead. , 1978, The Journal of laboratory and clinical medicine.

[20]  M. F. Sullivan,et al.  Effect of excess Fe on Cd or Pb absorption by rats. , 1987, Journal of toxicology and environmental health.

[21]  C. Gopinath,et al.  The role of microsomal hydroxylases in the modification of chloroform hepatotoxicity in rats. , 1975, British journal of experimental pathology.

[22]  Zhimin Chen,et al.  Relationship between vapor exposure and urinary metabolite excretion among workers exposed to trichloroethylene. , 1989, American journal of industrial medicine.

[23]  J. Barton,et al.  Factors affecting the absorption and excretion of lead in the rat , 1978 .

[24]  T. Dutkiewicz,et al.  The effect of mixed exposure to lead and zinc on ALA level in urine , 1979, International archives of occupational and environmental health.

[25]  R. Yip,et al.  Iron status of children with elevated blood lead concentrations. , 1981, The Journal of pediatrics.

[26]  S. Shima,et al.  Effect of food intake on blood lead concentration in workers occupationally exposed to lead. , 1987, Toxicology letters.

[27]  P. Brodal The Central Nervous System , 1992 .

[28]  S. Horvath,et al.  Human exposure to sulfur dioxide and ozone: absence of a synergistic effect. , 1979, Archives of environmental health.

[29]  M E Andersen,et al.  In vivo metabolic interactions of benzene and toluene. , 1990, Toxicology letters.

[30]  T. Clarkson,et al.  The depression of pulmonary retention of mercury vapor by ethanol: identification of the site of action. , 1973, Toxicology and applied pharmacology.

[31]  D. Pashley,et al.  Fluoride Reabsorption by Nonionic Diffusion in the Distal Nephron of the Dog , 1991, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[32]  A. Oskarsson,et al.  Increased lead levels in brain after long-term treatment with lead and dithiocarbamate or thiuram derivatives in rats. , 2009, Acta Pharmacologica et Toxicologica.

[33]  A. Backman,et al.  Trichloro-ethylene concentrations in blood and expired air as indicators of occupational exposure. A preliminary report. , 1972 .

[34]  M. Chamberlain,et al.  The relationship between iron and lead absorption in humans. , 1982, The American journal of clinical nutrition.

[35]  W. Schaffner,et al.  Carbon tetrachloride toxicity potentiated by isopropyl alcohol. Investigation of an industrial outbreak. , 1976, JAMA.

[36]  A. Bernard,et al.  The influence of orally-administered vitamin C or zinc on the absorption of and the biological response to lead. , 1983, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[37]  K. P. Dubois Combined effects of pesticides. , 1969, Canadian Medical Association journal.

[38]  A. Hofman,et al.  Decreased selenium levels in acute myocardial infarction. , 1989, JAMA.

[39]  Ragan Ha Effects of iron deficiency on the absorption and distribution of lead and cadmium in rats. , 1977 .

[40]  G. Pershagen,et al.  On the interaction between occupational arsenic exposure and smoking and its relationship to lung cancer. , 1981, Scandinavian journal of work, environment & health.

[41]  M. Ikeda,et al.  Symptoms and signs of workers exposed to benzene, toluene or the combination. , 1987, Industrial health.

[42]  J. Annest,et al.  Association of erythrocyte protoporphyrin with blood lead level and iron status in the second National Health and Nutrition Examination Survey, 1976-1980. , 1986, Environmental research.

[43]  J. Angerer,et al.  Occupational chronic exposure to organic solvents , 1990, International archives of occupational and environmental health.

[44]  K. Mahaffey Nutritional Factors and Susceptibility to Lead Toxicity , 1974, Environmental health perspectives.

[45]  J. Liira,et al.  Coexposure of man to m-xylene and methyl ethyl ketone. Kinetics and metabolism. , 1988, Scandinavian journal of work, environment & health.

[46]  Lee M. Alderman,et al.  EPIDEMIC MALATHION POISONING IN PAKISTAN MALARIA WORKERS , 1978, The Lancet.

[47]  R. Shamberger,et al.  Antioxidants and Cancer , 1976 .

[48]  J. Miles,et al.  S-Methyl isomer content of stored malathion and fenitrothion water-dispersible powders and its relationship to toxicity. , 1979, Journal of agricultural and food chemistry.

[49]  C. S. Yang,et al.  Induction of cytochromes P450IIE1 and P450IIB1 by secondary ketones and the role of P450IIE1 in chloroform metabolism. , 1989, Toxicology and applied pharmacology.

[50]  O. Levander,et al.  Selenium metabolism. VI. Effect of arsenic on the excretion of selenium in the bile. , 1966, Toxicology and applied pharmacology.

[51]  J. Menkes Letter: Toxic polyneuropathy due to methyl n-butyl ketone. , 1976, Archives of neurology.

[52]  B. A. Olson,et al.  Coexposure to toluene and p-xylene in man: central nervous functions. , 1985, British journal of industrial medicine.

[53]  G. Yost,et al.  Effect of alcohol and aldehyde dehydrogenase inhibitors on the toxicity of 3-nitropropanol in rats. , 1985, Toxicology and applied pharmacology.

[54]  R. Fontaine,et al.  Peripheral neuropathy in a coated fabrics plant. , 1974, Journal of occupational medicine. : official publication of the Industrial Medical Association.

[55]  G. Mulder,et al.  Inhibition of sulfate conjugation of N-hydroxy-2-acetylaminofluorene in isolated perfused rat liver and in the rat in vivo by pentachlorophenol and low sulfate. , 1980, Cancer research.

[56]  D. Bates,et al.  Respiratory effects of exposure to ozone plus sulfur dioxide in Southern Californians and Eastern Canadians. , 1977, American Industrial Hygiene Association journal.

[57]  Goyer Ra,et al.  The influence of iron deficiency on tissue content and toxicity of ingested lead in the rat. , 1972 .

[58]  V. Riihimäki Percutaneous absorption of m-xylene from a mixture of m-xylene and isobutyl alcohol in man. , 1979, Scandinavian journal of work, environment & health.

[59]  N. Solomons Competitive interaction of iron and zinc in the diet: consequences for human nutrition. , 1986, The Journal of nutrition.

[60]  J. Haist,et al.  Interrelationships between iron and lead absorption in iron-deficient mice. , 1979, Gastroenterology.

[61]  M. Lawson,et al.  The intake and excretion of lead and cadmium by the elderly. , 1984, The American journal of clinical nutrition.

[62]  S. Jacob,et al.  DIMETHYL SULFOXIDE: EFFECTS ON THE PERMEABILITY OF BIOLOGIC MEMBRANES (PRELIMINARY REPORT). , 1964, Current therapeutic research, clinical and experimental.

[63]  H. Moeller,et al.  Plasma and red blood cell cholinesterase activity as indications of the threshold of incipient toxicity of ethyl-p-nitrophenyl thionobenzenephosphonate (EPN) and malathion in human beings. , 1962, Toxicology and applied pharmacology.

[64]  H. Ganther Modification of methylmercury toxicity and metabolism by selenium and vitamin E: possible mechanisms. , 1978, Environmental health perspectives.

[65]  R. Charlson,et al.  Role of Relative Humidity in the Synergistic Effect of a Sulfur Dioxide-Aerosol Mixture on the Lung , 1973, Science.

[66]  F. N. Kudsk The influence of ethyl alcohol on the absorption of mercury vapour from the lungs in man. , 2009, Acta pharmacologica et toxicologica.

[67]  R. Tardif,et al.  Effect of simultaneous exposure to toluene and xylene on their respective biological exposure indices in humans , 1991, International archives of occupational and environmental health.

[68]  J. Mendell,et al.  Toxic polyneuropathy due to methyl n-butyl ketone. An industrial outbreak. , 1975 .

[69]  G. Schrauzer,et al.  Cancer mortality correlation studies--III: statistical associations with dietary selenium intakes. , 1977, Bioinorganic chemistry.