Observations in humans

The use of sodium chlorate as a weed killer has meant that a number of case reports concerning ingestion of large amounts of sodium chlorate are available. A review of 14 cases of sodium chlorate poisoning in patients whose ages ranged from 3 to 55 years demonstrated that doses in excess of 100 g (or 79 g as chlorate) were uniformly fatal. The lowest fatal dose was 15 g, equivalent to 196 mg chlorate/ kg bw in a 60-kg person (Helliwell Nunn, 1979). 

A series of studies have been conducted in human volunteers in a single laboratory. Written informed consent was obtained from each subject prior to 

Normal healthy adult male volunteers (10 per group) were then given 500 ml of water containing chlorine dioxide, chlorite, chlorate, chlorine or chloramine at 0 or 5 mg/l daily for 12 weeks. If one assumes a mean body weight of 70 kg, the dose of chlorite was equivalent to 0.036 mg/kg bw per day. Examinations included serum chemistry, blood count, urinalysis, special tests (e.g. thyroid hormones. 

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Toxicity. Many /V-nitrosamines are toxic to animals and cells in culture (4,6—8,88). /V-Nitrosodimethy1amine [62-75-9] (NDMA) is known to be acutely toxic to the Hver in humans, and exposure can result in death (89). Liver damage, diffuse bleeding, edema, and inflammation are toxic effects observed in humans as a result of acute and subacute exposure to NDMA. These effects closely resemble those observed in animals dosed with NDMA (89,90). 

Enhancement of the human HS response may eventually be a clinical goal in dealing with the aging population which may be more susceptible to environmental stress. Several investigators have now shown an age-dependent defect in the regulation of the HS response at the transcriptional level (Fargnoli et al., 1990). This defect has been observed in human peripheral blood lymphocytes and in... 

Tolerance is characterized by reduced responsiveness to the initial effects of a drug after repeated exposure or reduced responsiveness to a related compound (i.e., cross-tolerance). Animal studies have not provided conclusive evidence of tolerance to the effects of the centrally active compounds in toluene or trichloroethane (Moser and Balster 1981 Moser et al. 1985). Observations in humans, on the other hand, have documented pronounced tolerance among subjects who chronically inhale substances with high concentrations of toluene (Glaser and Massengale 1962 Press and Done 1967) and butane (Evans and Raistrick 1987). Kono et al. (2001) showed that tolerance to the reinforcing effects of solvents is comparable to that conditioned by nicotine but less intense than that reported with alcohol or methamphetamine use. 

Other additional studies or pertinent information that lend sunnort to this MRL Methyl parathion affects the nervous system by inhibiting acetylcholinesterase activity. Cholinesterase inhibition and neurological effects have been observed in humans and animals, for all exposure routes and durations (for example. Dean et al. 1984 Desi et al. 1998 EPA 1978e Gupta et al. 1985 Nemec et al. 1968 Suba 1984). 

An MRL of 0.1 ppm was derived for intermediate inhalation exposure (15-364 days) to trichloroethylene. This MRL was based on a study by Arito et al. (1994a) in which male JCL-Wistar rats were exposed to 0, 50, 100, or 300 ppm trichloroethylene for 6 weeks, 5 days/week, 8 hours/day. A LOAEL of 50 ppm was observed for decreased wakefulness during exposure, and decreased postexposure heart rate and slow wave sleep. Another study with rats found an increase in sleep-apneic episodes and cardiac arrhythmias after exposure to trichloroethylene (Arito et al. 1993). These results corroborate similar effects observed in humans exposed to trichloroethylene, as described in the previous paragraph, as well as evidence of organic solvent-induced sleep apnea in humans (Edling et al. 1993 Monstad et al. 1987, 1992 Wise et al. 1983). 

Effect. Biomarkers of effects are not available for trichloroethylene. There is no clinical disease state that is unique to trichloroethylene exposure. Interpretation of the behavioral observations in humans is complicated by many factors, such as possible irritant effects of the odor and nonspecific effects on the nervous system (e.g., fatigue). Further studies in this area would be useful in determining the exposure levels that may be... 

Immunological and Lymphoreticular Effects. Depressed white blood cell counts have been observed in humans and animals exhibiting relatively high body burdens of241 Am following accidental or... 

Organophosphate Ester Hydraulic Fluids. No studies regarding dermal effects in humans after inhalation or oral exposure were located. Erythema was observed in humans repeatedly exposed to dermal patches of Skydrol 500B-4 for an intermediate duration (Monsanto 1980). Skin scabbing was seen after oral exposure to Sanitizer 154 at 300 mg/kg (IRDC 1981). 

Studies performed using laboratory animals exposed to high concentrations of hydrogen sulfide gas have yielded results similar to those observed in humans exposed at high levels. Exposure of Sprague-Dawley rats to 1,655 ppm killed all 5 animals within 3 minutes (Lopez et al. 1989). All male Fischer-344 rats exposed to 500-700 ppm hydrogen sulfide gas for 4 hours died, while no rats died when exposed to concentrations up to 400 ppm under these conditions (Khan et al. 1990 Lopez et al. 1987, 1988a,... 

Effects observed in animals are similar to those that have been observed in humans. Death has occurred in animals after inhalation of high concentrations of hydrogen sulfide. Acute inhalation exposures to hydrogen sulfide have also resulted in respiratory, cardiovascular, neurological, hepatic, body weight, and developmental effects in animals. Gastrointestinal effects have been noted in animals after oral exposure to hydrogen sulfide. 

The Leggett Model simulates lead biokinetics in liver with two compartments the first simulates rapid uptake of lead from plasma and a relatively short removal half-life (days) for transfers to plasma and to the small intestine by biliary secretion a second compartment simulates a more gradual transfer to plasma of approximately 10% of lead uptake in liver. Different transfer rates associated with each compartment are calibrated to reproduce patterns of uptake and retention of lead observed in humans, baboons, and beagles following intravenous injection, as well as blood-to-liver concentration ratios from data on chronically exposed humans. Similarly, the Leggett Model simulates lead biokinetics in three compartments of soft tissues, representing rapid, intermediate, and slow turnover rates (without specific physiologic correlates). 

Studies in rodents, dogs, and non-human primates have demonstrated all of the major types of health effects of lead that have been observed in humans, including cardiovascular, hematological, neurodevelopmental, and renal effects (EPA 1986a). These studies also provide support for the concept of blood lead concentration as a metric of internal dose for use in dose-response assessments in humans. 

The lead-induced nephropathy observed in humans and rodents shows a comparable early pathology (Goyer 1993). However, in rodents, proximal tubular cell injury induced by lead can progress to adenocarcinomas of the kidney (see Section 2.2.3.8). The observation of lead-induced kidney tumors in rats may not be relevant to humans. Conclusive evidence for lead-induced renal cancers (or any other type of cancer) in humans is lacking, even in populations in which chronic lead nephropathy is evident. 

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