Acute toxicity lethality

Acute oral toxicity To determine the potential acute toxicity-lethality following a single oral dose... 

Acute inhalation toxicity To determine the potential acute toxicity-lethality following a single 4-h inhalation exposure to a test atmosphere containing the new pharmaceutical excipient (aerosol, vapor or particles)... 

The response time of a chemical sensor should be appropriate for the application for which it is intended. For example, if the sensor is used to monitor acutely toxic (lethal) substances in the workplace, the response time should be faster than the biological/ toxicological re.sponse — perhaps only a few seconds. On the other hand, some applications, such as monitoring the spread of a chemical waste plume underground, have characteristic time scales of days to years, permitting utilization of sensors that respond more slowly. 

CN AND CS Toxicity in Animals In animal studies, the cause of death from CN inhalation is the result of toxicity in the pulmonary system. Post-mortem examination from acute toxicity lethality studies in animals... 

Skin absorption and administration by intraperitoneal and intravenous routes exhibited high acute toxicity lethal dose in mice intraperitoneally was 4 mg/kg... 

L Acute Toxicity. Lethality data for agent GD are summarized in Table 28. The estimated oral LD50 value for humans is 5-20 Lig/kg (Somani et al. 1992). Gause et al. (1985) reported that the threshold for seizure induction in juvenile male baboons was 5 pg GD/kg when administered by i.m. injection. Bucci et al. (1992c) conducted range-finding studies with rats. The test material was administered by gavage to male and female CD rats once per day, 5 d/wk, for 2 wk. These studies indicated that the maximum dose tolerated by CD rats was... 

Equation 1 (TABLE 2) is the toxicity QSAR for this data set a slope of essentially negative one and r of 0.99 is achieved. Equation 2 is generated using equation 1 and the bioconcentration/Kow relationship of Halfon (1985). It indicates that a whole-body toxicant concentration of approximately 6,500 yumol L or 0.0065 mol L (or mol Kg when the density is about 1.0) is associated with an acutely toxic lethal response in half the exposed population of fathead minnows at essentially infinite time, i.e., threshold. 

According to Hodge and Sterner (1943) the REE are only slightly toxic and the extensive review by Haley (1979) similarly concluded that REE have a very low acute toxicity . Lethal dose rates for various species and routes of administration have been reported by Haley (1965). 

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. 

The propensity of nitriles to release cyanide subsequent to metaboHsm is the basis of their acute toxicity. Nitriles that form tertiary radicals at their alpha carbon atoms (eg, isobutyronitrile, 2-methylbutyronitrile) are substantially more acutely lethal than nitriles that form secondary radicals at their alpha carbons (eg, butyronitrile, propionitnle). Cyanohydrins are acutely toxic because they are unstable and release cyanide quickly. Alpha-aminonitriles are also acutely toxic, presumably by analogy with cyanohydrins. 

Health, Safety, and Environmental Factors. Sulfur dioxide has only a moderate acute toxicity (183). The lowest pubHshed human lethal concentration is 1000 ppm for 10 months. The lowest pubHshed human toxic concentration by inhalation is 3 ppm for 5 days or 12 ppm for 1 hour. The lowest pubHshed human lethal concentration is 3000 ppm for 5 months. In solution (as sulfurous acid), the lowest pubHshed toxic dose is 500 flg/kg causing gastrointestinal disturbances. Considerable data is available by other modes of exposure and to other species NIOSH standards are a time-weighted average of 2 ppm and a short-term exposure limit of 5 ppm (183). 

When making comparisons of lethal toxicity, it must be remembered that different mechanisms may be iavolved with different materials, and these need to be taken iato account. Also, comparisons of acute toxicity should take note of differences ia time to death, siace marked differences ia times between dosiag and death may influence ha2ard evaluation procedures and thek implications. In a few kistances, it may be possible to calculate two LD q values for mortaUty one based on early death due to one mechanism, and a second based on delayed deaths due to a different mechanism (69). 

Acute toxicity studies are often dominated by consideration of lethaUty, including calculation of the median lethal dose. By routes other than inhalation, this is expressed as the LD q with 95% confidence limits. For inhalation experiments, it is convenient to calculate the atmospheric concentration of test material producing a 50% mortaUty over a specified period of time, usually 4 h ie, the 4-h LC q. It is desirable to know the nature, time to onset, dose—related severity, and reversibiUty of sublethal toxic effects. 

The more soluble forms of barium such as the carbonate, chloride, acetate, sulfide, oxide, and nitrate, tend to be more acutely toxic (50). Mean lethal doses for ingested barium chloride were 300—500 mg/kg in rats and 7—29 mg/kg in mice (47). 

The LC50 is the lethal concentration of chemical (e.g. in air or water) that will cause the death of 50% of the sample population. This is most appropriate as an indicator of the acute toxicity of chemicals in air breathed (or in water, for aquatic organisms). Table 5.11 illustrates the use of LD50 values to rank the toxicity of substances. 

Marine toxins are not always acutely toxic. This may be particularly so for toxins which are used to deter competing occupants for living space since they often have comparatively slow actions on growth. With such toxins, the procedures for the evaluation of acutely lethal toxins cannot apply. However, interesting discoveries may be made by using the simplest of screen of alcoholic extracts for cytolytic actions as exemplified in Table I of Shier 109),... 

Acute Toxicity. The LD50 following oral administration of parathion, either in propylene glycol solutions or in aqueous suspensions of the 15% wettable powder, has been determined for rats, mice, and guinea pigs. The lethal dose was approximated for rabbits and dogs. The results of these experiments are summarized in Table I. Statistical evaluation was by the method of Wilcoxon and Litchfield (11). 

Lazar (http //lazar.in silico.de/predict) is a k-nearest-neighbor approach to predict chemical endpoints from a training set based on structural fragments [43]. It derives predictions for query structures from a database with experimentally determined toxicity data [43]. Model provides prediction for four endpoints Acute toxicity to fish (lethality) Fathead Minnow Acute Toxicity (LC50), Carcinogenicity, Mutagenicity, and Repeated dose toxicity. 

Witkin (1956) reported intravenous (i.v.), i.p., and oral LD50 (lethal dose for 50% of the animals) values for mice and rats, and i.v. LD50 values for dogs. Similar to hydrazine, the route of administration had minimal effect on the LD50 within species. Generally, monomethylhydrazine and 1,2-dimethylhydrazine appeared to be somewhat more potent in mice and rats than was hydrazine. Results of this study showed that the 1,1-dimethylhydrazine was less acutely toxic than hydrazine or the other hydrazine derivatives. 

Lethal human toxicity values have not been established or have not been published. However, based on available information, this material appears to have a considerably greater acute toxicity than HC1 gas (C11-A063). 

In all cases, the concentrations of malathion and fenitrothion measured in water (up to 5.8 and 1.2 pg/L, respectively) were below the LC50 (lethal concentration 50%) values reported for these compounds in oysters and mussels, which range between 2.7 and 278 mg/L in the case of malathion, and between 10.3 pg/L and 123 mg/L in the case of fenitrothion (http //www.pesticideinfo.org). However, it has to be stressed that these LC50 values express acute toxicity, that both malathion and fenitrothion might be bioaccumulated by molluscs (as their detection in biota suggests), and that aquatic organisms are exposed to a variety of contaminants, some of which could show synergetic or additive effects [40]. Further matters of... 

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