Lethal concentration definition

A lethal concentration is one which the average uiiprotectonumerical value of the lethal concentration dwreaKos as the time of exposure inereas( s. 

Endpoint/Concentration/Rationale Because the exposures did not result in effects consistent with the definition of an AEGL-3, the concentration vs percent hemoglobin formation data presented by the authors was graphed and projected to a methemoglobin level of 70-80%, which was considered the threshold for lethality in humans. This value was approximately 250 ppm. An 8-h exposure to 250 ppm was chosen as the basis for the AEGL-3 calculations. 

Based upon the available data, derivation of AEGL-1 values was considered inappropriate. The continuum of arsine-induced toxicity does not appear to include effects consistent with the AEGL-1 definition. The available human and animal data affirm that there is a very narrow margin between exposures that result in little or no signs or symptoms of toxicity and those that result in lethality. The mechanism of arsine toxicity (hemolysis that results in renal failure and death), and the fact that toxicity in humans and animals has been reported at concentrations at or below odor detection levels (-0.5 parts per million (ppm)) also support such a conclusion. The use of analytical detection limits (0.01 to 0.05 ppm) was considered as a basis for AEGL-1 values but was considered to be inconsistent with the AEGL-1 definition. 

Numerous cases of arsine poisoning have been reported (Elkins and Fahy 1967 DePalma 1969). However, these reports lack definitive exposure concentration data and usually lack exposure duration data as well. Some of the more recent and complete reports involving nonlethal consequences are described in the following section. These reports do not provide quantitative data suitable for AEGL derivations, but they do provide valuable insight into the nature and progression of arsine poisoning in humans. In most cases, the severity of the effects was usually sufficient to necessitate medical intervention to prevent lethality. Some of the more prominent reports and those with the best descriptive data have been summarized, but the overview is by no means exhaustive. 

Numerous case reports are available regarding the lethal and nonlethal toxicity of arsine in humans, but definitive exposure concentration or duration data are lacking. Although the case reports are of limited use for quantitative estimates of exposure limits, they do provide qualitative information about the nature of arsine poisoning in humans. Some estimated human toxicity values are available and are summarized in Table 2-3. 

Test Species/Strain/Sex/Number Squirrel monkeys, 2-4 males/group Exposure Route/Concentrations/Durations Inhalation exposure at 300,340, or 376 ppm for 15 min 130, 150, or 170 ppm for 30 min 75, 85, or 90 ppm for 60 min Effects Data specifically identifying serious, irreversible effects consistent with the AEGL-2 definition were not available. The lethality data are shown in the summary table for AEGL-3. 

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. 

A review of 139 methadone-related deaths between 1998 and 2002 in Palm Beach County supported those of previous investigations and suggested that it is not possible to establish a definitive lethal methadone blood concentration range. Methadone-related death is usually associated with the use of other drugs and toxicological analysis in such cases should be contextualized by the clinical circumstances surrounding the event and even a few months before the incident occurred (50). 

The definition of the acute to chronic ratio (ACR) has been one of the methods used to predict the threshold concentration at which a toxicant does not produce noticeable effects during a chronic exposure. This ratio is based on the same concept as the application factors, but its numerical value is the inverse (Stephan, 1982). The ACR is the ratio between chemical concentrations exerting a lethal versus sublethal toxic effect and describes the ratio of a lethal to sublethal end-point ... 

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