Lethality, acute toxicity tests

TABLE 5.3. Information, Including Lethality, that can be Gained in Acute Toxicity Testing... 

DePass, L. (1989). Alternative approaches in median lethality (LD5o) and acute toxicity testing. Tox. Lett. 49 159-170. 

There are some other acute toxicity tests in which non-lethal outcome are sought. These include studies of the amount of chemical needed to cause skin or eye irritation or more serious damage. Test systems developed by J. H. Draize and his associates at the Food and Drug Administration in the early 1940s were used to study ocular effects. Warning labels on consumer products were typically based on the outcome of the Draize test. 

Acute toxicity refers to the adverse effects, which occur within a given, usually short time, following a single, usually high exposure to a substance. In older literature, acute toxicity is sometimes used synonymously with lethal effect or LD50, which was the only endpoint in older acute toxicity tests. Nowadays, acute toxicity studies are designed to reveal more subtle effects. 

Lee G, Ellersieck MR, Mayer FL, Krause GF. 1995. Predicting chronic lethality of chemicals to fishes from acute toxicity test data multifactor probit analysis. Environ Toxicol Chem 14 345-349. 

The guidance value ranges proposed for single-dose exposure which has produced a significant non-lethal toxic effect are those applicable to acute toxicity testing, as indicated in Table 3.8.1. 

Dead is an unambiguous criterion. In acute toxicity tests the dose is determined at which half of the animals die (so-called LD50 or lethal dose 50%). 

How close do the above estimates relate to the actual LD50 Studies have shown that the approximate lethal dose for 86% of those chemicals tested in this manner were within 30% of the known LD50 values determined by the classical approach. The method is not infallible for example, some 14% of chemicals were outside this range and no dose-response or slope information can be obtained. International agreement has been reached that the up-and-down procedure could replace the conventional acute toxicity test for the purposes of hazard classification and label (including color-coding) production. 

There are some other acute toxicity tests in which non-lethal outcomes are sought. These include studies of the amount of chemical needed to cause skin or eye irritation or more serious damage. Test... 

The acute toxicity test which is mostly used describes the adverse biological effect or effects which occur within a short period of time after a short-term exposure. The results are often expressed as the LC50 or EC50 (median lethal or median effect concentration) values which are statistically derived concentrations which over a defined period of exposure in an acute toxicity test are expected to cause death or effects in 50% of the organism in a given period (24, 48 or 96 h). 

In addition to its usefulness as a rough scale of chemicals relative potencies as lethal agents, acute-toxicity testing also provides preliminary information on two other important characterisdcs of toxicity. Information about the reversibility of toxicity can be obtained by coundng the number of animals in each dosage group that. 

In summary, acute-toxicity testing in small mammals such as rats provides a range of valuable information on chemical toxicity, including lethal doses by different routes of exposure, mechanism(s) of lethal toxicity, the extent to which the lethal effect may be reversible in some members of the exposed population while others die, and the relative potencies of toxic chemicals as lethal agents. 

It is likely that the lethal cardiotoxicity caused by high doses of ionophores in acute toxicity tests, the positive inotropy (increased force of heart contraction, causing an increase in blood flow from the heart) produced at lower doses, and the myopathy in skeletal muscles and neurotoxicity are probably all related to ion flow disrupting properties. It is plausible that there is a common mechanism for these effects of polyether ionophore coccidiostats. When such a common mechanism of toxicity exists for a group of substances, the default assumption is that their toxicity will be additive. As such, the ionophoric effects of polyether coccidiostats in a mixed exposure may be regarded as additive, whilst the toxicological properties of coccidiostats that are not due to disruption of ion flows are less likely to be caused by a common mechanism and are not considered to be additive. 

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. 

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