Human Case Studies

There are some 30,000 chemical waste dump sites in the United States. Many of these were established in the 1950s and 1960s when little was known about the need to contain the wastes buried in them. One such site is located in Hardeman County, Tennessee, where residents were exposed to leachate from that toxic waste dump in the drinking water drawn from nearby wells. The contaminants detected in these wells include the following chemicals  

Those who were exposed to the contaminated drinking water sustained multiple liver effects compared with controls who were not exposed to this water. The effects included increased elevation of alkaline phosphatase and serum glutamic oxaloacetic transaminase as well as significantly lower albumin and total bilirubin levels. I32l 

Five workers at an industrial waste treatment plant in Ulsan, Korea, developed acute toxic hepatitis following the introduction of a new disposal process that resulted in their exposure to a large number of lipophilic and hydrophilic volatile organic compounds. The chemicals they were exposed to included 

2- Butoxyethanol Butyl acetate Cyclohexanone Dimethyl acetamide 

Severe destruction of liver cells with bridging necrosis was observed in all five patients. None of the individual chemicals in the mixture had known toxicology that matched the clinical characteristics that were observed. The authors of the study suggest that the various chemicals detected in the analysis underwent an interaction among themselves, which synergistically raised their toxicity compared with the original material. I33 

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No studies were located regarding excretion of methyl parathion in humans following inhalation exposure. The limited information available from human case studies indicates that the chemical s metabolites are rapidly excreted primarily in the urine in humans following oral (Morgan et al. 1977) or dermal (Ware et al. 1974, 1975) exposure and in animals following oral (Hollingworth et al. 1973) or dermal (Abu-Qare et al. 2000) exposure. 

No studies have been conducted to evaluate the reproductive effects of endrin aldehyde or endrin ketone in humans or animals via the inhalation, oral, and dermal routes of exposure. Additional animal studies and further human case studies are needed to determine the potential reproductive hazard and to determine threshold levels for effects that may exist via all three of these routes of exposure. 

In experiments carried on in the author s laboratory several years ago, the B vitamin content of milks from individual cows and from individual human mothers was determined.63 So far as this study is concerned, involving as it did only B vitamins, the intra-individual variation (that is, from day to day) appeared to be greater than interindividual differences. The number of human cases studied was not sufficient to be the basis of any sound conclusion on this point. 

Most of the data described in this section were derived from laboratory studies in which 1,4-dichlorobenzene was administered to test animals via gavage. In addition, two human case studies of... 

Based on a combination of available human case studies and experiments with laboratory animals, the major public health concerns associated with exposure to 1,4-dichlorobenzene are effects on the liver, kidneys, and blood. Some immunological, dermatological, and neurological effects have also been reported in exposed humans. There is information from animal studies which raises the question of whether 1,4-dichlorobenzene can cross the placenta and elicit structural effects on the developing fetus. Data from a study conducted in rats using the intraperitoneal route have demonstrated sperm abnormalities. Cancer of the liver as a result of lifetime exposure to 1,4-dichlorobenzene has been shown in mice, and renal cancer has been reported in male rats. However, recent studies related to the mechanism of renal carcinogenesis in rats suggest that these tumors may not be expected to occur in exposed humans. Issues relevant to children are explicitly discussed in Section 2.6, Children s Susceptibility, and Section 5.6, Exposures of Children. 

Samples of stomach contents, blood, bile, adipose tissue, liver, brain, and kidney were collected at autopsy of a woman who ingested a lethal dose estimated at 293 mg/kg of a diazinon formulation ("FERTI-LOME" bagworm spray) containing 10% diazinon (Poklis et al. 1980). The highest concentrations were found in the blood, followed by stomach contents and the bile. Lowest concentrations were found in the kidney, followed by adipose tissue, and then bile. Animal studies confirmed the human case study in that diazinon is widely distributed in all analyzed tissues in rats (Miicke et al. 1970), in sheep (Janes et al. 1973 Machin et al. 1971, 1974), and in cows (Abdelsalam and Ford 1986). 

Hematological Effects. In human case studies of oral barium poisoning, a decrease in serum potassium is frequently observed in the subjects (Diengott et al. 1964 Gould et al. 1973 Lewi and Bar-Khayim 1964 Phelan et al. 1984 Talwar and Sharma 1979 Wetherill et al. 1981). 

Several studies of animals exposed to barium by parenteral routes indicate that barium decreases in serum potassium (Foster et al. 1977 Jaklinski et al. 1967 Roza and Berman 1971 Schott and McArdle 1974). In one study, dogs intravenously administered barium chloride demonstrated a decrease in serum potassium accompanied by an increase in red blood cell potassium concentration (Roza and Berman 1971). The authors concluded that the observed hypokalemia was due to a shift of potassium from extracellular to intracellular compartments and not to excretion. Additional intravenous studies have linked the observed hypokalemia to muscle paralysis in rats (Schott and McArdle 1974) and cardiac arrhythmias in dogs (Foster et al. 1977). These experiments in animals strongly support the suggestive human case study evidence indicating hypokalemia is an important effect of acute barium toxicity. 

The subcommittee reviewed data that came primarily from human experimental studies and from toxicity studies in various animal species. The evaluation focused on inhalation exposure studies that measured respiratory irritation and tolerance to odor. Human case studies, accident reports, and epidemiologic studies of industrial exposures were extensive but of limited use to the subcommittee because they lack quantitative exposure measurements. Controlled human experiments were most important to the subcommittee for establishing the SEALs for ammonia. There appears to be a broad range of sensitivity to ammonia s pungent odor and in irritation caused by exposures to low concentrations... 

Although definitive scientific data are not available on oral absorption of benzene in humans, case studies of accidental or intentional poisoning indicate that benzene is absorbed by the oral route (Thienes and Haley 1972). 

Although the primary effect of mercury on the kidneys appears to be a direct toxic effect on the renal tubules, there is also evidence that implicates an immune mechanism of action for mercury-induced glomerular toxicity in some persons. In support of this theory, a few human case studies have reported deposition of IgG, immune complexes, and/or complement C3 along the glomerular basement membrane (Lindqvist et al. 1974 Tubbs et al. 1982). 

Renal effects were not observed in dogs exposed intermittently to 25 ppm 1,1-dimethylhydrazine for 13-26 weeks (Rinehart et al. 1960). Mild renal effects including amyloidosis and mineralization were observed in hamsters exposed intermittently to 0.25 ppm hydrazine for 1 year (Vemot et al. 1985) however, no effects were noted in the kidneys of mice exposed intermittently to 1 ppm hydrazine for 1 year (Vemot et al. 1985). The findings of these animal studies are inconsistent with the severe effects observed in the human case study. However, more severe effects on the kidney have been observed in animals exposed to hydrazines by other routes (see Sections 2.2.2.2 and 2.4). 

RDX has been detected in the serum, urine, and feces of one child who consumed unknown levels of RDX in the form of C-4 (91 % RDX). RDX was measured in the serum for 120 hours and in the feces for 144 hours after the presumed time of ingestion (Woody et al. 1986). The metabolities of RDX have only been found in animals by using a radiolabel ( C) (Schneider et al. 1977). Although this study found the radiolabel in the breath, urine, and feces, the chemical identity of the metabolites was not described. Therefore, metabolites cannot currently be used as biomarkers. In the one available human case study, RDX was found in the body following a single exposure, but no data are available regarding intermediate or chronic exposures. 

Patch test concentrations that may be used for maneb and mancozeb range from 0.2-1% in petrolatum, respectively, reported in a review of patch testing procedures (Fisher 1983). Patch test concentrations used in human case studies that have yielded positive results range from 0.2 to 1. % for maneb (Adams and Manchester 1982 Crape et al. 1990 List and Carragheen 1985 Magnesia et al. 1988 Nader et al. 1979) and... 

Patch testing in some human case studies show some cross-reactivity between various dithiocarbamate compounds and other chemically-similar compounds. Burry et al. (1976) reported cross reactions between Mankobunt (active ingredient mancozeb) and Zineb 65 (active ingredient polymeric zinc ethylene... 

Use by indigenous people of devil s club in diabetes has been recorded, though several human case studies and animal studies have provided equivocal results in evaluating effects on blood sugar levels, and no contemporary substantiation of efficacy in diabetes was found (Lantz et al. 2004 Smith 1983 Stuhr and Henry 1944 Thommassen et al. 1990). 

In the last several decades, there have been several studies in experimental animals, case reports in humans, case studies in humans, and epidemiological studies in humans on the effects of solvents on the kidney, both acutely and chronically. The scope of diis chapter is the clinical chronic effects of solvents on the kidney (chronic nephrotoxicology). 

JC Kraft, W Slikker, JR Bailey, LG Roberts, B Fischer, W Wittfoht, H Nau. Plasma pharmacokinetics and metabolism of 13-cis retinoic and iill-trans retinoic acid in the cynomolgus monkey and the identification of 13-cis retinoyl beta-glucuro-nides—a comparison to one human case-study with isotretinoin. Drug Metab Dispos 19 317-324, 1991. 

Creech Kraft J, Slikker Jr, W, Bailey JR, Roberts LG, Fischer B, Wittfoht W, Nau H (1991) Plasma pharmacokinetics of 13-cw- and all-rraw5-retinoic acid in the Cynomolgus monkey and the identification of the conjugate metabolites 3-cis and all-rran -retinoyl-P-glucuronides a comparison to one human case study with Isotretinoin. Drug Metab Dispos 19 317-324... 

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