Acute causes

FIGURE 13—4. Pharmacology of cocaine. Cocaine is a powerful inhibitor of the dopamine transporter. Blocking this transporter acutely causes dopamine to accumulate, and this produces euphoria, reduces fatigue, and creates a sense of mental acuity. Cocaine has similar but less important actions at the norepinephrine and serotonin transporters. 

Noticeably improved acutance caused by edge effects at tonal boundaries. 

Mrs GG has atrial fibrillation which if not controlled can cause temporary loss of cardiac output resulting in a drop of blood pressure. Mrs GG s description of suddenly going dizzy associated with a jump in the chest suggest that her fall was probably caused by this. Her sudden dizziness is consistent with an arrhythmia and not some other acute cause such as epilepsy. 

Fig. 10.6. AT2-weighted (a) and diffusion-weighted (b) MRI in a 60-year-old woman who had awoken three weeks before with slurred speech. On examination, there was very mild dysarthria. Several white matter hyperintensities are seen on the T2-weighted image but the acute causative lesion in seen clearly in the diffusion-weighted image.

UVB (290-320 run) is 1000 times more active than UVA, acutely causes simburn and tanning, and chronically skin cancer and skin aging... 

The mechanisms of antiseizure actions of VNS are unknown, but recent studies have indicated that VNS acutely causes widespread bilateral cortical and subcortical alterations in blood flow, suggesting that it affects synaptic activity in humans. ... 

I6I C. Warfarin baits need contain only 0 025% active principle, and rats are killed after ingesting about 5 doses the bait can be left down and the risk of acute toxicity to man or domestic animals is not serious. In common with other coumarin derivatives, warfarin reduces the clotting power of blood and death is caused by haemorrhages initiated by any slight injury. Warfarin is a vitamin K antagonist, and large oral doses of the vitamin can be given as an antidote. 

As a class of compounds, the two main toxicity concerns for nitriles are acute lethality and osteolathyrsm. A comprehensive review of the toxicity of nitriles, including detailed discussion of biochemical mechanisms of toxicity and stmcture-activity relationships, is available (12). Nitriles vary broadly in their abiUty to cause acute lethaUty and subde differences in stmcture can greatly affect toxic potency. The biochemical basis of their acute toxicity is related to their metaboHsm in the body. Following exposure and absorption, nitriles are metabolized by cytochrome p450 enzymes in the Hver. The metaboHsm involves initial hydrogen abstraction resulting in the formation of a carbon radical, followed by hydroxylation of the carbon radical. MetaboHsm at the carbon atom adjacent (alpha) to the cyano group would yield a cyanohydrin metaboHte, which decomposes readily in the body to produce cyanide. Hydroxylation at other carbon positions in the nitrile does not result in cyanide release. 

Toxicity studies on trifluoroethanol show acute oral LD q, 240 mg/kg acute dermal LD q, 1680 mg/kg and acute inhalation L(ct) Q, 4600 ppmh. Long-term subchronic inhalation exposure to 50—150 ppm of the alcohol has caused testicular depression in male rats, but no effects were noted at the 10 ppm level (32). Although the significance of the latter observations for human safety is unknown, it is recommended that continuous exposure to greater than 5 ppm or skin contact with it be avoided. 

Health and Safety Factors. VDE is a flammable gas its combustion products are toxic. Liquid VDE on contact with the skin can cause frostbite. Acute inhalation toxicity of VDE is low median lethal concentrations (LC q) for rats were 128,000 ppm after a single 4-h exposure (52) and 800,000 ppm after a 30-min exposure (53). Cumulative toxicity is low exposure of rats and mice at levels of up to 50,000 ppm for 90 days did not cause any... 

The short-term or acute effects of the P-agonists may be different from chronic effects. Acute Hpolysis and glycogenolysis are not observed beyond the first day or two of treatment. Exact mechanisms of action on Hpid metaboHsm may differ among species. Chronic effects of the P-agonists reduce circulating insulin concentrations ST treatment causes an opposite change. Whereas residue levels may be of concern with adrninistration of several of the P-agonists, such is not the case for ST or GRE. 

Hydraziae is toxic and readily absorbed by oral, dermal, or inhalation routes of exposure. Contact with hydraziae irritates the skin, eyes, and respiratory tract. Liquid splashed iato the eyes may cause permanent damage to the cornea. At high doses it can cause convulsions, but even low doses may result ia ceatral aervous system depressioa. Death from acute exposure results from coavulsioas, respiratory arrest, and cardiovascular coUapse. Repeated exposure may affect the lungs, Hver, and kidneys. Of the hydraziae derivatives studied, 1,1-dimethylhydrazine (UDMH) appears to be the least hepatotoxic monomethyl-hydrazine (MMH) seems to be more toxic to the kidneys. Evidence is limited as to the effect of hydraziae oa reproductioa and/or development however, animal studies demonstrate that only doses that produce toxicity ia pregaant rats result ia embryotoxicity (164). 

Aromatic Hydrocarbons. These are the most toxic of the hydrocarbons and inhalation of the vapor can cause acute intoxication. Benzene is particularly toxic and long-term exposure can cause anemia and leukopenia, even with concentrations too low for detection by odor or simple instmments. The currendy acceptable average vapor concentration for benzene is no more than 1 ppm. PolycycHc aromatics are not sufftcientiy volatile to present a threat by inhalation (except from pyrolysis of tobacco), but it is known that certain industrial products, such as coal tar, are rich in polycycHc aromatics and continued exposure of human skin to these products results in cancer. 

Methanol is not classified as carcinogenic, but can be acutely toxic if ingested 100—250 mL may be fatal or result in blindness. The principal physiological effect is acidosis resulting from oxidation of methanol to formic acid. Methanol is a general irritant to the skin and mucous membranes. Prolonged skin contact with methanol vapor or Hquid can cause dermatitis. Methanol vapor can cause eye and respiratory tract irritation, nausea, headaches, and dizziness. 

Toxicology. The acute oral and dermal toxicity of naphthalene is low with LD q values for rats from 1780—2500 mg/kg orally (41) and greater than 2000 mg/kg dermally. The inhalation of naphthalene vapors may cause headache, nausea, confusion, and profuse perspiration, and if exposure is severe, vomiting, optic neuritis, and hematuria may occur (28). Chronic exposure studies conducted by the NTP ia mice for two years showed that naphthalene caused irritation to the nasal passages, but no other overt toxicity was noted. Rabbits that received 1—2 g/d of naphthalene either orally or hypodermically developed changes ia the lens of the eye after a few days, foUowed by definite opacity of the lens after several days (41). Rare cases of such corneal epithelium damage ia humans have been reported (28). Naphthalene can be irritating to the skin, and hypersensitivity does occur. 

Acute oral LD q data for nitro alcohols in mice are given in Table 1. Because of their low volatiHty, the nitro alcohols present no vapor inhalation ha2ard. They are nonirritating to the skin and, except for 2-nitro-1-butanol, are nonirritating when introduced as a 1 wt % aqueous solution in the eye of a rabbit. When 0.1 mL of 1 wt % commercial-grade 2-nitro-1-butanol in water is introduced into the eyes of rabbits, severe and permanent corneal scarring results. This anomalous behavior may be caused by the presence of a nitro-olefin impurity in the unpurifted commercial product. 

Inhalation is the chief route of worker exposure. Comparative data from acute or subchronic inhalation exposures with rats (98) indicate that nitromethane and nitroethane are the least toxic of the nitroparaffins by this route and do not induce methemoglobin formation. The nitropropanes are less well tolerated 2-nitropropane is more toxic than 1-nitropropane and is more likely to cause methemoglobinemia. 

Health and Safety Factors, Toxicology. Phosphoms trichloride severely bums skin, eyes, and mucous membranes. Contaminated clothing must be removed immediately. Vapors from minor inhalation exposure can cause delayed onset of severe respiratory symptoms after 2—24 h, depending on the degree of exposure. Delayed, massive, or acute pulmonary edema and death can develop as consequences of inhalation exposure. 

Acute Toxicity. Plasticizers possess an extremely low order of acute toxicity LD q values are mostiy in excess of 20,000 mg/kg body weight for oral, dermal, or intraperitoneal routes of exposure. In addition to thek low acute toxicity, many years of practical use coupled with animal tests show that plasticizers do not kritate the skin or mucous membranes and do not cause sensitization. 

Liver Effects. In 1980 a 2-year feeding study carried out as part of the NTP/NCI Bioassay Program in the United States (38,39) indicated that DEHP causes increased incidence of Hver tumors in rats and mice and that DEHA had a similar effect in mice but not rats. In these studies the levels of plasticizers fed were very high, this being possible only because of thek low acute toxicity. 

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