Acute toxicity systemic effects

The priority effects are carcinogenicity, mutagenicity, reproductive or developmental toxicity, endocrine disruption and neurotoxicity. Human toxicity is broader than priority effects, including acute toxicity, systemic toxicity (organ effects), immune system effects and skin/eye/respiratory damageaswellasthepriority effects. And toxicity as T includes both human toxicity and ecotoxicity. 

Pharmacologically, carbofuran inhibits cholinesterase, resulting in stimulation of the central, parasympathetic, and somatic motor systems. Sensitive biochemical tests have been developed to measure cholinesterase inhibition in avian and mammalian brain and plasma samples and are useful in the forensic assessment of carbamate exposure in human and wildlife pesticide incidents (Bal-lantyne and Marrs Hunt and Hooper 1993). Acute toxic clinical effects resulting from carbofuran exposure in animals and humans appear to be completely reversible and have been successfully treated with atropine sulfate. However, treatment should occur as soon as possible after exposure because acute carbofuran toxicosis can be fatal younger age groups of various species are more susceptible than adults (Finlayson et al. 1979). Carbofuran labels indicate that application is forbidden to streams, lakes, or ponds. In addition, manufacturers have stated that carbofuran is poisonous if swallowed, inhaled, or absorbed through the skin. Users are cautioned not to breathe carbofuran dust, fumes, or spray mist and treated areas should be avoided for at least 2 days (Anonymous 1971). Three points are emphasized at this juncture. First, some carbofuran degradation... 

Dihydroxybenzenes (DHBs) are slightly more acutely toxic than phenol (Table 5). Contact with dihydroxybenzene through oral, dermal, or respiratory routes can induce significant systemic exposure. Skin or eye effects have been demonstrated during chronic or accidental professional exposure. No systemic effect has been described in such circumstances. 

Toxicology. The nitroparaffins have minimal effects by way of actual contact. There were neither systemic effects nor irritation in dermal studies in rabbits. Human exposure of a prolonged or often-repeated nature has led to low grade irritation attributable to removal of oil from the skin, an effect produced by most organic solvents. Eye irritation potential of all four nitroparaffins has been deterrnined in rabbits. Other than a transient slight redness and some lachrymation, no effects were noted. The average Draize score was 0.0. The acute oral toxicity, LD q, of all four nitroparaffins has been deterrnined in the rat (Table 8). 

Enzyme Inhibition. Some materials produce toxic effects by inhibition of biologically vital enzyme systems, leading to an impairment of normal biochemical pathways. The toxic organophosphates, for example, inhibit the cholinesterase group of enzymes. An important factor in thek acute toxicity is the inhibition of acetylocholinesterase at neuromuscular junctions, resulting in an accumulation of the neurotransmitter material acetylcholine and causing muscle paralysis (29) (see Neuroregulators). 

Acute Toxicity Studies. These studies should provide the following information the nature of any local or systemic adverse effects occurring as a consequence of a single exposure to the test material an indication of the exposure conditions producing the adverse effects, in particular, information on dose—response relationships, including minimum and no-effects exposure levels and data of use in the design of short-term repeated exposure studies. 

Trichloroethylene is acutely toxic, primarily because of its anesthetic effect on the central nervous system. Exposure to high vapor concentrations is likely to cause headache, vertigo, tremors, nausea and vomiting, fatigue, intoxication, unconsciousness, and even death. Because it is widely used, its physiological effects have been extensively studied. 

An exposure to a specific chemical in relatively low concentrations over a period may result in chronic effects. At higher concentrations, the effects may be acute. Some chemicals produce local damage at their point of contact with, or entry into, the body others produce systemic effects, i.e. they are transported within the body to various organs before exerting a toxic effect. 

No NOAELs or LOAELs were identified for toxic effects in humans after inhalation exposure to organophosphate ester hydraulic fluids. Reliable NOAELs and LOAELs for acute inhalation exposure are restricted to 4-hour NOAELs for systemic effects in rats exposed to Fyrquel 220 or Durad MP280 and 4-hour LOAELs for mild lethargy in rats exposed to Durad MP280 and Fyrquel 220 (Gaworski et al. 1986). The study identifying these NOAEL and LOAEL values did not measure cholinesterase inhibition, did not allow sufficient follow-up time for the development of delayed neurotoxic effects, and used a... 

Mineral Oil Hydraulic Fluids. There is limited information on the toxicity of mineral oil hydraulic fluids in humans. A single case report of a child accidentally ingesting a single dose of automotive transmission fluid provides limited information on death and systemic effects. A case-control study provides some information on the carcinogenicity of mineral oil hydraulic fluids. The study population was exposed via inhalation and dermal routes. An occupational exposure study provides information on neurotoxicity following chronic dermal exposure. Information on the toxicity of mineral oil hydraulic fluids is limited to a series of inhalation, oral, and dermal acute-duration exposures. These studies provide information on death, systemic effects, and neurotoxicity by inhalation, oral, and dermal routes, and immunotoxicity following dermal exposure. 

Organophosphate insecticides also inhibit RBC-ACHE and PCHE. Inhibition of ACHE in erythrocytes is assumed to mirror inhibition of ACHE in the nervous system, which is the receptor of the toxic action, to some extent. Therefore, measurements of RBC-ACHE and PCHE are used for biological monitoring of exposure to OP insecticides (Maroni, 1986). Inhibitions of RBC-ACHE and PCHE activities are correlated with intensity and duration of exposure, although at different levels for each OP compound. Blood ACHE, being the same molecular target as that responsible for acute toxicity in the nervous system, is a true indicator of effect, while PCHE can only be used as an indicator of exposure. 

Figure 2-4 summarizes areas concerning the health effects of acrylonitrile where studies have and have not been performed. There are some data available on the effects in humans following acute or chronic exposure to acrylonitrile via the inhalation route of exposure. The target organ for acute toxicity is the nervous system. Chronic exposure to acrylonitrile has been associated with cancer. However, many of the available reports lack quantitative information on exposure levels. In humans,... 

The precise mechanism of monomethylhydrazine toxicity is uncertain. In addition to the contact irritant effects, the acute toxicity of dimethylhydrazine exposure probably involves the central nervous system as exemplified by tremors and convulsions (Shaffer and Wands 1973) and behavioral changes at sublethal doses (Streman et al. 1969). Additionally, renal and hepatic toxicity and hemolytic effects imply alternate mechanisms of toxicity. 

The precise mechanism of dimethylhydrazine toxicity is uncertain. In addition to the contact irritant effects, the acute effects of dimethylhydrazine exposure may involve the central nervous system as exemplified by tremors and convulsions (Shaffer and Wands 1973) and behavioral changes at sublethal doses (Streman et al. 1969). Back and Thomas (1963) noted that the deaths probably involve respiratory arrest and cardiovascular collapse. The central nervous system as a target is consistent with the delayed latency in response reported for dimethylhydrazine (Back and Thomas 1963). There is some evidence that 1,1-dimethylhydrazine may act as an inhibitor of glutamic acid decarboxylase, thereby adversely affecting the aminobutyric acid shunt, and could explain the latency of central-nervous-system effects (Back and Thomas 1963). Furthermore, vitamin B6 analogues that act as coenzymes in the aminobutyric acid shunt have been shown to be effective antagonists to 1,1-dimethylhydrazine toxicity (reviewed in Back and Thomas 1963). 

In mammals, phenobarbital and phenytoin increase serum ceruloplasmin concentrations (Aaseth and Norseth 1986). Chronic copper poisoning in sheep is exacerbated when diets contain heliotrope plants (Heliotropium sp., Echium spp., Senecio sp.). Aggravated effects of the heliotrope plants include reduced survival and a twofold to threefold increase in liver and kidney copper concentrations when compared to control animals fed copper without heliotropes (Howell et al. 1991). Rats given acutely toxic doses of 2,3,7,8-tetrachlorodibenzo-para-dioxin had elevated concentrations of copper in liver and kidney because of impaired biliary excretion of copper (Elsenhans et al. 1991). Morphine increases copper concentrations in the central nervous system of rats, and dithiocarbam-ates inhibit biliary excretion (Aaseth and Norseth 1986). In human patients, urinary excretion of copper is increased after treatment with D-penicillamine, calcium disodium EDTA, or calcium trisodium diethylenetriamine penta acetic acid (Flora 1991). 

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