Lethal dose and

In laboratory tests, appHcation of DMAC to the skin of pregnant rats has caused fetal deaths when the dosages were close to the lethal dose level for the mother. Embryonal malformations have been observed at dose levels 20% of the lethal dose and higher. However, when male and female rats were exposed to mean DMAC concentrations of 31,101, and 291 ppm for 6 h per day over several weeks, no reproductive effects were observed (6). 

Hydrazine and all of its methylated derivatives appear to induce neuromuscular disorders at or near lethal doses, and all appear to be respiratory irritants. Jacobson et al. (1955) noted that the actions of hydrazine and its methylated derivatives were similar all are respiratory irritants and convulsants. In addition, monomethylhydrazine also induced severe intravascular hemolysis in dogs. 

Burns from liquid exposure to over 50% of the body surface suggest that the individual has received/absorbed more than a lethal dose and the prognosis is poor. 

Toxic collar, as above. Each coyote tested was known to have fatally attacked at least 3 domestic sheep within a 30-day period Of the 12 coyotes that attacked the neck region of the sheep and punctured the collar, 9 received lethal doses and became immobilized in 1-3 min and died 3-25 min later. The mean time to death was 11.6 min. One of the three sublethally dosed coyotes survived at last three successful attacks in which the collar was punctured, and two survived two attacks. In all cases, contact with NaCN produced shaking of the head, pawing at the mouth, rubbing the snout on the ground, and ataxia 4... 

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. 

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

The more classical approach to assess the presence of marine biotoxins in seafood is the in vivo mouse bioassay. It is based on the administration of suspicious extracted shellfish samples to mice, the evaluation of the lethal dose and the toxicity calculation according to reference dose response curves, established with reference material. It provides an indication about the overall toxicity of the sample, as it is not able to differentiate among individual toxins. This is a laborious and time-consuming procedure the accuracy is poor, it is nonspecific and generally not acceptably robust. Moreover, the mouse bioassay suffers from ethical implications and it is in conflict with the EU Directive 86/609 on the Protection of Laboratory Animals. Despite the drawbacks, this bioassay is still the method of reference for almost all types of marine toxins, and is the official method for PSP toxins. 

In order to compare the safety and efficacy of drugs and their formulations, the therapeutic index, an estimate of therapeutic effects in relation to side effects, is often used (Figure 5.9B).The dose or concentration of a drug needed to ehcit a therapeutic effect in 50% of the population (median effective dose) is called the ED50. Typically a median lethal dose or LD50 is characterized for each drug in relevant experimental animals. The relationship of median lethal dose and effective dose comparison is the therapeutic index ... 

Renal effects which were seen at near-lethal doses and considered secondary to frank toxicity included pale kidneys in minks after acute oral exposure to 2,3,7,8-TCDD (Hochstein et al. 1988), and enlarged convoluted tubules and Bowman s spaces together with epithelial hyperplasia in rats (Christian et al. 

In the toxicity studies the maximum administered dose was identified as the NOAEL. A traditional lethal dose study was not performed. Instead, the relationship between dose levels and toxicity were evaluated. These studies demonstrated that r-haGAL had extremely low toxicity. It was unlikely that a clear toxic dose could have been identified for r-haG AL given that r-haGAL cannot be sufficiently concentrated to deliver a lethal dose and test animals... 

When tests are performed on terrestrial animals, it is common to apply single (measured) doses orally, topically (i.e., applied to the skin or cuticle), or by injection into tissues or body fluids. There can be very large differences among groups of organisms and among species in their susceptibility to the toxic action of chemicals. The selective toxicity ratio (SER) is expressed in terms of the median lethal dose, and is important for the differentiation between beneficial organisms and pests ... 

How do scientists, and toxicologists in particular, assess the risk from chemicals and what does their assessment mean Sometimes we can assess the risk of a particular activity from past experience and knowledge. With poisoning cases we know that if someone eats or drinks more than a particular amount of potassium cyanide or Weedol (paraquat) they are likely to die. Hence the risk in an individual poisoning case can be estimated from the known lethal dose and the amount that the victim has eaten, drunk, or inhaled. 

ICt5Q varies with concentration ECtS0 =1,500 Very rapid incapacitation can occur within 1 to 2 minutes of exposure to an incapacitating or lethal dose, and death can occur within 15 minutes of receiving a lethal dose... 

The Food and Drug Administration requires that medication undergo rigorous testing before approving the medication. Testing includes the following animal studies to determine the medication s therapeutic index. A therapeutic index is a ratio between the median lethal dose and the median effective dose and indicates the safe dose to administer to the patient to achieve the therapeutic effect. These tests also provide scientists with information on how the medication is absorbed, distributed, metabolized, and excreted. 

Terrorists are unlikely to use therapeutic, cosmetic botulinum toxin (FDA approved in 2002) because the commercial preparation contains only 0.3% of the injectable lethal dose and 0.005% of the lethal oral dose (37). 

Gombar VK, Enslein K, Hart JB, Blake BW, Borgstedt HH. Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR. Risk Anal 1991 Sep ll(3) 509-17. 

In most cases of death through nicotine poisoning the total nicotine content of the various organs is far in excess of the lethal dose and is distributed throughout the stomach and gastrointestinal tract, liver, heart, kidneys, as well as lungs, blood and spleen. 

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