Neurotoxicity acute

Henderson, J.D., RJ. Higgins, L. Rosenblatt and B.W. Wilson. 1989. Toxicity Studies on Agent GA Delayed Neurotoxicity - Acute and Repeated Exposures to GA (Tabun). Einal Report, U.S. Army Medical Research and Development Command, Fort Detrick, MD. 

Heptane is toxic to the human nervous system (neurotoxic). Acute exposure symptoms include distorted perception and mild hallucinations. Humans exposed to 0.1% (1000 ppm) heptane exhibited dizziness in 6 min higher concentrations caused marked vertigo and incoordination. Humans accidentally exposed to high concentrations showed similar symptoms, as well as mucous membrane irritation, nausea, and lassitude. All these symptoms pass quickly upon recovery in fresh air, but the recovery period is longer than that for pentane or hexane. A gasoline aftertaste has been experienced by people who have been experimentally exposed to heptane. 

Neurotoxicity. Acute-duration human studies via the inhalation route (Carpenter et al. 1975a, 1975b Gamberale et al. 1975 Hastings et al. 1984 Larsen and Schmunes 1974 Pedersen and Cohr... 

Henderson JD, Higgins RJ, Rosenblatt L, Wilson BW. Toxicity Studies on Agent GA Delayed Neurotoxicity—Acute and Repeated Exposures of GA (Tabun). Davis, Calif University of California Davis Lab for Energy 1989. 

Henderson JD, Higgins RJ, Rosenblatt D, Wilson BW (1989) Toxicity studies on agent GA delayed neurotoxicity—acute and repeated exposures to GA (tabun). DTIC AD A219457. U.S. Department of the Army, Medical Research and Development Command, Fort Detrick, MD. 

In a cross-sectional study, exposure and effect are studied simultaneously. This approach contains an inherent problem because exposure must precede the effect. However, it can he used to investigate acute effects and also mild chronic effects (which do not force people to leave their jobs) if exposure has remained rather stable for a long time. When the prevalence of the effects studied are compared with the prevalence in other worker groups (controls or references) which correspond otherwise with the study group but are not exposed to the agent investigated, indicative evidence of possible causality may be obtained. For example, cross-sectional studies have been applied successfully to reveal the associations between mild neurotoxic effects and exposure to organic solvents. ... 

Organic solvents have acute narcotic effects. Aromatic and chlorinated hydrocarbons seem to be especially effective. As stated, the combined effect of several organic solvents is usually considered to be additive. However, there is some evidence that the combined effect may in fact be synergistic. The symptoms caused by organic solvents, often called prenarcotic symptoms, resemble those caused by the use of alcohol. A decrease in reaction time and impairment in various psychological performances can be observed. Acute neurotoxicity can also be detected as abnormalities in the electroencephalogram (EEG i, which records the electrical activity of the brain. " ... 

Neurotoxicity (damage to the nervous system by a toxic substance) may also be seen with the administration of the aminoglycosides. Signs and symptoms of neurotoxicity include numbness, skin tingling, circum-oral (around the mouth) paresthesia, peripheral paresthesia, tremors, muscle twitching, convulsions, muscle weakness, and neuromuscular blockade (acute muscular paralysis and apnea). 

No acute oral MRL was derived for methyl parathion because data regarding the most sensitive effect that was observed after acute oral exposure are conflicting. Increased pup mortality and altered behavior occurred in offspring of rats exposed to 1 mg/kg/day methyl parathion during, but no effects on pup survival or on sensitive electrophysiological indices of neurotoxicity were seen at virtually the same dose, 0.88 mg/kg/day, in a similar developmental toxicity study. 

The database for the health effects of methyl parathion after ingestion in experimental animals is substantial. However, as can be seen in Figure 3-5, only limited information is available on the effects of inhalation and dermal exposure to methyl parathion in animals. Furthermore, the health effects such as death and neurotoxicity resulting from acute exposure in animals are more fully studied than systemic and immunotoxic effects associated with acute exposure. 

Neurotoxicity. Information in both humans and animals indicates that the nervous system is the major target of methyl parathion-induced toxicity following acute exposure by any route (Daly 1989 Dean et al. 1984 EPA 1978e Fazekas 1971 Gupta et al. 1985 Nemec et al. 1968 Roberts et al. 1988 Suba 1984 Yamamoto et al. 1982 Youssef et al. 1987). The most prominent signs of acute exposure to methyl... 

In summary, neurotoxic effects of endosulfan are usually apparent only after acute ingestion of relatively high doses. Cumulative neurotoxicity does not appear to be significant. If the animal survives the acute toxic effects, then no long-term neurotoxic effects are evident from behavioral, gross, and microscopic observations. However, some impairment may occur that can be detected only by specialized neurobehavioral testing. 

In summary, the frank neurotoxic effects of endosulfan are apparent only after acute ingestion of relatively high doses in animals. However, long-term decreased psychomotor function, possibly resulting from acute endosulfan exposure, have been reported by two authors (Aleksandrowicz 1979 Shemesh et al. 1988). Such effects cannot be easily measured in animals. Hence, the fact that long-term neurotoxic effects have not been observed in animals does not mean that such effects caimot occur in humans. However, no information was located that indicated that persons exposed to low levels of endosulfan might experience any neurotoxicity. 

Acute clinical signs of neurotoxicity, manifested by hyperexcitability, dyspnea, decreased respiration, tremors, and convulsions, were identified in the available literature as effects caused by high doses of endosulfan. Exposure to high levels of endosulfan in humans may possibly be associated with permanent brain damage as manifested by cognitive and emotional deterioration, memory impairment, and... 

The data in animals are insufficient to derive an acute inhalation MRL because serious effects were observed at the lowest dose tested (Hoechst 1983a). No acute oral MRL was derived for the same reason. The available toxicokinetic data are not adequate to predict the behavior of endosulfan across routes of exposure. However, the limited toxicity information available does indicate that similar effects are observed (i.e., death, neurotoxicity) in both animals and humans across all routes of exposure, but the concentrations that cause these effects may not be predictable for all routes. Most of the acute effects of endosulfan have been well characterized following exposure via the inhalation, oral, and dermal routes in experimental animals, and additional information on the acute effects of endosulfan does not appear necessary. However, further well conducted developmental studies may clarify whether this chemical causes adverse developmental effects. 

In terms of toxicity, NIOSH recommends that endosulfan be recognized as a Group 1 Pesticide (NIOSH 1992). Pesticides in Group 1 pose a significant risk of adverse acute health effects at low concentrations or carcinogenic, teratogenic, neurotoxic, or reproductive effects (NIOSH 1992). 

When OCs were phased out, the less persistent insecticides that replaced them were thought to be more environment friendly. However, some of the insecticides that were used as replacements also presented problems because of very high acute toxicity. The insecticides to be discussed in this chapter illustrate well the ecotoxi-cological problems that can be associated with compounds that have low persistence but high neurotoxicity. 

The rapid growth in the use of OPs and the proliferation of new active ingredients and formulations was not without its problems. Some OPs proved to be too hazardous to operators because of very high acute toxicity. A few were found to cause delayed neurotoxicity, a condition not caused by ChE inhibition (e.g., mipafox, lepto-phos). There was also the problem of the development of resistance, for example, by... 

---