Lethal dose , median

Table 11 summarizes values for the median lethal dose (LD q) for several species. In case of massive exposure, convulsions must be controlled, and glucose, fluid balance, and uriaary output must be maintained. Medical surveillance requires checking for damage to the Hver, the organ that apparently sustains initial damage, and monitoring for changes ia the blood profile. 

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 body excretes tritium with a biological half-life of 8—14 d (10.5 d average) (75), which can be reduced significantly with forced fluid intake. For humans, the estimated maximum permissible total body burden is 37 MBq (1 mCi). The median lethal dose (LD q) of tritium assimilated by the body is estimated to be 370 GBq (10 Ci). Higher doses can be tolerated with forced fluid intake to reduce the biological half-life. 

LD5f (median lethal dose) A standard measure of toxicity indicating the dose of a substance that will kill 50% of a group of test organisms. 

The median lethal dose of lunacrine hydrochloride is 78-7 3-8 mgm. per kilo given intravenously in mice. Oral doses of 1 gramme of lunamarine are not fatal. The m.l.d. of lunacridine by mouth is 1,097 167 mgra. per kilo. Limamarine stimulates isolated rabbit intestine and uterus, but lunacrine and lunacridine inhibit peristaltic movement of the isolated intestine. All three alkaloids reduce arterial blood pressure in cats. ... 

Median Lethal Dose (LD) The statistically derived single dose of a chemical that can be c.xpected to cause death in 50% of a given population of organisms under a defined set of experimental conditions. This figure has often been used to classify and compare toxicity among chemicals but its value for this purpose is doubtful. One commonly used classification of this kind is as follows ... 

Therapeutic index. Ratio between the median lethal dose CLDso) and the median effective dose CED30) of a drug. 

As discussed earlier, selectivity is the consequence of the interplay between toxicokinetic and toxicodynamic factors. Some examples are given in Table 2.8, which will now be briefly discussed (data from Walker and Oesch 1983, and Walker 1994a,b). These and other examples will be described in more detail under specific pollutants later in the text. In the table, comparisons are made between the median lethal doses or concentrations for different species or strains. Comparisons are made of data obtained in lethal toxicity tests where the same route of administration was used for species or strains that are compared. The degree of selectivity is expressed... 

Compound Organism Test Median Lethal Dose or Concentration... 

Median Lethal Dose (MLD)—Dose of radiation required to kill, within a specified period (usually 30 days), 50% of the individuals in a large group of animals or organisms. Also called the LD50, or LD50/30 if for 30 days.. 

Karel, L. and Weston, R.E. 1947. The biological assay of inhaled substance by the dosimetric method The retained median lethal dose and the respiratory response in unanesthetized, normal goats exposed to different concentrations of phosgene. J. Ind. Hyg. Toxicol. 29 23— 28. 

Weston, R.E. and Karel, L. 1946. An application of the dosimetric method for biologically assaying inhaled substances The determination of the retained median lethal dose, percentage retention, and respiratory response in dogs exposed to different concentrations of phosgene. J. Pharmacol. Exptl. Ther. 88 195. 

Finney, D. (1985). The median lethal dose and its estimation. Arch. Toxicol. 56 215-218. 

Acute Lethality. The median lethal dose (LD g) of MCB to rainbow trout was estimated to be 1.8 ml/kg at 24 h. No mortalities were observed in any of the treated animals after this time. The 24 h LD50 value for CCI4 was estimated to be 4.75 ml/kg but, unlike fish treated with MCB, fish intoxicated with CCI4 continued to die throughout the entire 96 h observation period. 

Ibogaine has demonstrated toxic effects, which could potentially limit its usefulness in treating addiction. However, the proper dosage of alternative iboga alkaloids may avert this problem. The median lethal dose of ibogaine is 82 mg/kg in the guinea pig and 327 mg/kg in the rat (Dhahir 1971 Delourme-Houde 1946). Use of ibogaine for addiction treatment has been associated with two deaths overseas. 

Hodson, P.V., Dixon, D.G., and Kaiser, K.L.E. Measurement of median lethal dose as a rapid indication of contaminant toxicity... 

Selected entries from Methods in Enzymology [vol, page(s)] Median effective dose, 235, 29, 31, 33 determination of median infectious dose, 235, 29-39 median lethal dose, 235, 29 moving average interpolation, 235, 32-34, 36-37, 39 probit analysis, 235, 31-36, 39 Reed-Muench method, 235, 30, 33-35 staircase method, 235, 33, 37-39 median response, 235, 29 dose range for animal experiments, 235, 29 50% end-point determination, 235, 29-30. 

The dose of a substrate which is likely to cause death in an organism. It is symbolized by LD and is usually supplemented with a subscript number indicating the percentage of test animals that died the absolute lethal dose is LDioo, the median lethal dose is LD50, and the minimal lethal dose is LD05. These values will vary with the type of test animal and the route of administration hence, that information should always be provided. 

Toxicity of many entries are expressed quantitatively as LD50 (median lethal dose) or LC50 (median lethal concentration in air). The latter refers to inhalation toxicity of gaseous substances in air. Both these terms refer to the calculated concentration of a chemical that can kill 50% of test animals when administered. 

The FDA has made it clear that the duration of the study and the place where the study is conducted do not determine whether or not the study is GLP-regulated. Thus, the GLPs apply to short-term studies (e.g., median lethal dose studies and irritation studies) as well as long-term studies that meet all of the above criteria, and the GLPs apply to such studies whether conducted in a manufacturer s lahora-tories, in a university laboratory, or at a contract or subcontract facUity. The FDA expects GLP compliance for studies conducted in foreign countries as well as for those conducted within the United States. 

Sister chromatid exchange Bone marrow c5dogenetic In vivo cytogenetic In vitro mutation In vivo micronucleus Chromosomal aberration Median lethal dose (LD50)... 

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