Acute exposure definition

Case reports are available regarding lethal effects of acute exposure to arsine (Pinto et al. 1950 Morse and Setterlind 1950 Hesdorffer et al. 1986). However, no definitive quantitative exposure data accompany these reports. Signs and symptoms varied depending on the exposure situation but usually included abdominal and muscle pain, nausea and diarrhea, hematuria, and oliguria. Delayed lethality, common in arsine poisoning, varied considerably. 

There are no definitive data regarding the metabolism of arsine. Based upon proposed mechanisms of action and the known interaction with RBCs and hemoglobin, metabolism per se may of limited importance relative to acute exposures to arsine. Delayed toxicity and lethality are observed in both humans and animals following acute exposure to arsine, and it is known that increased... 

Data on acute exposures of humans to both isomers of dimethylhydrazine are limited to case reports of accidental exposures. Signs and symptoms of exposure include respiratory irritation, pulmonary edema, nausea, vomiting, and neurologic effects. However, definitive exposure data (concentration and duration) were unavailable for these accidents. The limited data in humans suggest that the nonlethal toxic response to acute inhalation of dimethylhydrazine is qualitatively similar to that observed in animals. No information was available regarding lethal responses in humans. In the absence of quantitative data in humans, the use of animal data is considered a credible approach for developing AEGL values. 

The human experience regarding exposure to dimethylhydrazines is limited to case reports describing severe but nonlethal effects following accidental acute exposures. There are limited data suggesting subclinical hepatotoxicity following subchronic occupational exposure to unspecified low levels of 1,1-dimethylhydrazine. No definite exposure concentrations or durations were available in these reports, and the data are not useful for quantitative derivation of AEGLs. 

House (1964) conducted 90-d continuous exposure studies of male Sprague-Dawley rats exposed to 1,1-dimethylhydrazine at average concentrations of 0.56 ppm. Mean exposure concentration over the first 10 d was 0.43 ppm. Definitive information regarding responses and biologic effects during the first day of exposure were not provided. Because laboratory data were recorded only at 30, 60, and 90 d, no inference could be made regarding potential effects of acute exposures from the House (1964) summary. 

Additionally, chronic drug use has been linked to neuropsychological problems that in turn make it harder to stop the cycle of abuse. Psychoactive drugs by definition affect the brain, and long-term or acute exposure to psychoactive substances can be toxic. Furthermore, we know that drug abuse can increase the risks of stroke, brain injury related to accidents, malnutrition, or liver damage, all of which can adversely affect brain function as well. 

Few data were available that met the definitions of AEGL end points. One inhalation study with 20 human subjects described headaches and slight loss of balance at exposure concentrations of 0.1 to 1.5 ppm for exposure durations of up to 8 h (Stewart et al. 1974). Acute exposure of monkeys for 6 h at concentrations ranging between 70 and 100 ppm resulted in severe signs of toxicity including convulsions but no deaths (Jones et al. 1972). In the same study, exposure of rats at a higher concentration, 189 ppm for 4 h, resulted in no toxic signs. Examination of the relationship between exposure duration and concentration for both mild and severe headaches in humans over periods of 1 to 8 h determined that the relationship is C xt=k. 

Few data on acute exposures with effects that meet the definition of an AEGL-2 were located. No clinical signs of intoxication were observed in rats exposed to PGDN at 189 ppm for 4 h. The methemoglobin level was 23.5% (Jones et al. 1972). Exposure of monkeys to PGDN at a concentration of 33 ppm for 4 h failed to affect performance in an operant avoidance behavioral test but altered the VER (Mattsson et al. 1981). 

Early work with sulfur dioxide showed a linear relationship between visible injury and reduction in yield for many crop species. The assessment was made that no reduction in yield would be found unless visible injury were noted. Definitive research with ozone, other oxidants, or mixtures of these pollutants with other gases has not been done. Thus, we do not know whether such relationships between visible injury and yield hold for the oxidants, but data in Table 11-3 suggest that for acute exposures there may be good correlations between injury and yield reductions. Many researchers have hypothesized that the oxidants may have an effect on plants that will produce a yield reduction with little or no visible injury. Such studies need to be designed in a more defmitive manner before it is concluded that yield reductions without visible symptoms are clearly acceptable. Projections of yield losses have made use of some of the data reported earlier. ... 

Single-dose toxicity studies fall into two categories preliminary and definitive studies. Preliminary studies are performed to provide an estimate of the maximum nonlethal dosage (MNLD) for use in definitive studies. Definitive studies are performed to evaluate effects that may result from acute exposure to the MNLD and predict effects of overdosage in man. 

It is interesting that the grave effects of pulmonary edema and hemorrhage from acute exposure of ozone may be prevented in animals by so simple a procedure as a combination of vitamins and reducing agents prior to ozone exposure (Table VI). The clues furnished by such substances on the mechanism of action of ozone, and related oxidative pulmonary irritants such as nitrogen dioxide, are considerable from such information a definitive hypothesis of action of these pulmonary irritants may be formulated and tested. 

Although every person who has duties which could give rise to health problems should be a participant, it is especiaUy critical to include permanent employees. Many of the tests which are run on the individual have a sufficiently wide normal range (except in extreme cases of acute exposure, where the individual should definitely receive medical attention anyway) that a single examination may not be particularly informative. However, problems due to environmental work conditions, as will be discussed later, may be revealed by trends shown by comparison of successive examinations. 

Occupational reactive airways dysfunction syndrome (RADS) is defined as persistent respiratory symptoms and nonspecific airway hyperreactivity in patients with a history of acute exposure to an inhaled agent (gas or aerosol) and no prior history of allergies, smoking, or asthma (25). The definition of RADS can usefully be extended in the WTC context (Table 1) to include those with repeated irritant exposure who have developed irritant-induced asthma. RADS can progress to irreversible lower airways obstructive disease. 

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. 

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