Animal studies lethal dose

Numerous studies provided doses associated with death following exposure to CDDs in animals. LD50 (lethal dose, kill for 50% of dosed animals during a certain time interval) values for each congener varied not only among species, but also among different strains. 

The lethal effect from cyanide poisoning varied with species. Investigating the acute oral toxicity of sodium cyanide in birds, Wiemeyer et al. (1986) observed that the LDso values for the flesh-eating birds were lower than that for the birds that fed on plant material vulture 4.8 mg/kg versus chicken 21 mg/kg. In a study on marine species, Pavicic and Pihlar (1983) found that at 10 ppm concentration of NaCN, invertebrates were more sensitive than Ashes. In animals, the lethal dose of NaCN were in the same range by different toxic routes. A dose of 8 mg NaCN/kg resulted in ataxia, immobilization, and death in coyotes (Sterner 1979) however, the lethal time was longer, at 18 minutes. 

Chinese Herbal Medicines. Many traditional Chinese medicines have been screened for radioprotective activity in experimental animals. In one study of more than a thousand Chinese herbs, a number of agents increased the survival rate of dogs exposed to a lethal dose of y-rays by 30—40%, and some symptoms of radiation injury were ameHorated. These effects are potentially related to stimulation of the hemopoietic and immune systems (130). Extracts of five Chinese dmg plants, as weU as aspirin, effectively protected mice exposed to 7.5—8.0 Gy (750—800 rad) of y-radiation, and increased survival rates by 8—50% (131). Several Chinese traditional medicines, adininistered ip before or after irradiation, protected against Hpid peroxidation in a variety of mouse tissues, including BM, Hver, and spleen, as weU as in mouse Hver microsomal suspensions irradiated in vitro (132). 

Death following treatment with a lethal dose of 2,3,7,8-TCDD is often delayed for several weeks. Among the animals which died following treatment, approximately half the deaths occurred between 13 and 18 days after treatment, with one animal dying as late as 43 days after a single oral dose. In mice and rabbits, there is a marked individual difference in susceptibility to this compound which makes it difficult to conduct acute lethality studies. 

Protection Studies. Animals were given a sublethal dose of palytoxin followed at various time intervals by a lethal dose. Control and treatment data for each route of administration and species studied are given in the appropriate table (Tables III, IV, V, and VI). 

A study in pairs of calves given 62.5, 125, 250, 500, or 1,000 mg/kg diisopropyl methylphosphonate in a gelatin capsule (Palmer et al. 1979) showed that animals at the highest dose displayed acute gastroenteritis and ecchymotic hemorrhaging. However, no effects were seen at non-lethal doses. It is not expected that persons living near the RMA and exposed to low levels of diisopropyl methylphosphonate would experience gastrointestinal effects. 

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. 

Earlier studies demanded calculation of an LD50 value (i.e. the quantity of the drug required to cause death of 50 per cent of the test animals). Such studies required large quantities of animals, were expensive, and attracted much attention from animal welfare groups. Its physiological relevance to humans was often also questioned. Nowadays, in most world regions, calculation of the approximate lethal dose is sufficient. 

Renal Effects. No studies were located regarding renal effects in humans after dermal exposure to endrin. Diffuse degenerative changes of the kidney occurred in rabbits exposed dermally to lethal doses of endrin once or for an intermediate duration (Treon et al. 1955). No studies were located regarding renal effects in humans or animals after dermal exposure to endrin aldehyde or endrin ketone. 

Death. Clinical reports in humans and studies in animals demonstrate that death due to central nervous system toxicity is the primary acute lethal effect associated with endrin exposure. A lethal dose of endrin in humans has not been identified, but 0.2-0.25 mg endrin/kg body weight is sufficient to cause convulsions (Davies and Lewis 1956). Liver, kidney, heart, and brain damage were reported following oral and inhalation exposures. Since endrin is no longer used commercially, the general public is not... 

Neurological Effects. Depression, disorientation, and collapse have been reported in humans with acute exposure to toxic closes of 1,2-dibromoethane by oral (Saraswat et al. 1986) or dermal (Letz et al. 1984) routes. Residues of 1,2-dibromoethane were detected in the brain tissue of one fatality (Letz et al. 1984). The fact that the nervous system is at risk when humans are acutely exposed to lethal doses is supported by animal studies (Rowe et al. 1952). 

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