Behavioral effects high-dose exposure effect

There have been descriptions of the acute toxic effects in humans that follow high-dose exposure (>LD5o) to the nerve agents soman (Lekov et al., 1966 Sidell, 1974), sarin (Sidell, 1974 Inoue, 1995 Nakajima et al., 1998), and VX (Nozaki et al., 1995). The same cluster of behavioral symptoms that are reported following lower doses (anxiety, psychomotor depression, intellectual impairment, and sleep disturbances) dominate the clinical picture in the immediate period following resolution of the acute toxic signs of intoxication and then slowly fade with time, sometimes taking months to fiiUy resolve. 

Neurological Effects. No studies were located regarding neurological effects in humans after exposure to hexachloroethane. Inhalation, oral, and dermal exposure of animals to moderate or high doses (260 ppm, 5,900 ppm, 375 mg/kg/day, 750 mg/kg/day) resulted in hyperactivity, tremors, fasciculation of the facial muscles, ataxia, convulsions, and/or prostration (Fowler 1969b NTP 1977, 1989 Southcott 1951 Weeks et al. 1979). Reduced motor activity has also been observed following oral exposure of pregnant rats (167 mg/kg/day) (Shimizu et al. 1992). Inhalation exposure of rats to 260 ppm for 6 weeks did not have any effect on spontaneous motor activity or shock avoidance behavior (Weeks et al. 1979). 

Inhalation exposure to high chloroform concentrations induced narcosis (Lehmann and Flury 1943 Sax 1979) and reversible impairment of memory retrieval in animals. High, single, oral doses of chloroform caused ataxia, incoordination, anesthesia, and brain hemorrhage in mice (Balster and Borzelleca 1982 Bowman et al. 1978). Behavioral effects were observed at lower oral doses. 

Acute exposure to high doses of lindane is known to cause CNS stimulation (usually developing within 1 hour), mental/motor impairment, excitation, clonic (intermittent) and tonic (continuous) convulsions, increased respiratory rate and/or failure, pulmonary edema, and dermatitis. Toxic symptoms in humans are more behavioral in nature (e.g., loss of balance, teeth grinding, and hyperirritability. Most acute effects in humans have been the result of accidental or intentional ingestion, although inhalation toxicity occurred (especially among children) when lindane was used in vaporizers. 

Repeated inhalation or oral exposures to moderate to high doses of -butyl acetate and -butanol are well tolerated. These aforementioned molecules are readily and rapidly metabolized to -butyric acid. The no-observed-effect level (NOEL) for repeated dose oral exposure to -butanol was 125 mg kg day. In a 90 day inhalation study in rats with -butyl acetate a NOEL of 500 ppm was reported for systemic effects, and a NOEL of 3000 ppm (highest dose tested) was reported for postexposure neurotoxicity based on functional observational battery endpoints, quantitative motor activity, neuropathy, and sched-uled-controlled operant behavior endpoints. Results of inhalation studies conducted on -butanol and -butyl acetate were negative for inducing reproductive and developmental toxicity. The NOEL for female reproductive toxicity was 6000 ppm with -butanol and 1500 ppm for -butyl acetate. In a 90 day repeated-dose inhalation toxicity study with butyl acetate the NOEL for male reproductive toxicity was 3000 ppm. For developmental toxicity, a NOEL of 3500 ppm was observed with -butanol and a NOEL of 1500 ppm (the highest exposure tested) was seen in both rats and rabbits following exposure to -butyl acetate. 

Many poisons can disturb mental and rational function leading to behavioral abnormalities. Psychototoxins include phencyclidine, LSD, and fungal toxins. Less commonly, stimulants such as cocaine and amphetamine can cause psychiatric problems. Psychiatric effects of high doses of corticosteroids have also been described. In addition to the developmental retardation, some investigators believe that cognitive impairment, hyperactivity, and perhaps even antisocial behavior may be caused by childhood lead exposure. Public discussion of these subtle toxic effects is highly politicized because childhood exposure to lead still occurs as a risk factor in slums and tenements. 

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