Delayed deaths

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). 

A.n log ue Synthesis. Two notable examples, in which analogues have greater therapeutic indexes than the parent dmgs, have been identified in Phase I trials. These are carboplatin (29) and ado2elesin (37) (35). Carboplatin s approval was based on its comparable efficacy to cis-platinum (28) and its more favorable toxicity profile, ie, reduced and delayed episodes of emesis, reduced ototoxicity, etc. On the other hand, ado2elesin, a totally synthetic analogue of natural product CC1065, has demonstrated a similar potency and antitumor activity profile as its natural prototype but is devoid of the delayed death UabiUty associated with the parent dmg in animals (36). 

The threshold limit value—time integrated average, TLV—TWA, of chlorine dioxide is 0.1 ppm, and the threshold limit value—short-term exposure limit, STEL, is 0.3 ppm or 0.9 mg /m of air concentration (87,88). Chlorine dioxide is a severe respiratory and eye irritant. Symptoms of exposure by inhalation include eye and throat irritation, headache, nausea, nasal discharge, coughing, wheezing, bronchitis, and delayed onset of pulmonary edema. Delayed deaths occurred in animals after exposure to 150—200 ppm for less than one hour. Rats repeatedly exposed to 10 ppm died after 10 to 13 days of exposure. Exposure of a worker to 19 ppm for an unspecified time was fatal. The ingested systemic effects of low concentration chlorine dioxide solutions are similar to that of chlorite. 

FIGURE 5.2. Example of dose probe method with delayed deaths. Source Schultz and Fuchs, 1982. 

Livers from toxin-injected mice showed severe congestion whether or not the mice survived the initial critical 2-hour post injection period. Occasionally, a mouse injected with a nominally lethal dose of toxin-LR survived the critical two hours but remained listless until it died several hours or several days later. The reasons for the delayed death are unknown. Such mice developed focal fatty degeneration of the liver and active regeneration of liver cells. 

Examination of 13 individuals 5 years after they were occupationally exposed to a chlorine dioxide leak revealed sensitivity to respiratory irritants and nasal abnormalities. Delayed deaths occurred in animals after exposure to 15 0-2 00 ppm for less than 1 hour. Rats exposed daily to 10 ppm died after 10-13 days of exposure effects were nasal and ocular discharge and dyspnea autopsy revealed purulent bronchitis. Another study reported that two to four 15-minute exposures to 5 ppm for 1 month did not alter the blood composition or lung histology of rats similar exposures to 10-15 ppm caused bronchitis, bronchiolitis, catarrhal alveolar lesions, and peribronchial infiltration. Lesions healed within 15 days after treatment. Rats and rabbits exposed for 30 days to 5 or 10 ppm (2 hours/day) had localized bronchopneumonia with elevated leukocyte counts slight reversible pulmonary lesions were found after exposures of 2.5ppm for 4-7 hours/day. No adverse reactions were... 

Concentrations near 30,000ppm were lethal to rats within 15 minutes toxic signs included loss of coordination and narcosis. This level of exposure produced pulmonary edema, and in cases of delayed deaths, there was interstitial pneumonitis. Concentrations as low as 3 000 ppm for 15 minutes produced light narcosis in rats. No toxic effects were observed in rats, rabbits, and dogs exposed 7 hours/day, 5 days/week for 14 weeks to... 

Cats exposed to 1900 ppm for six 8-hour exposures showed irritation of the eyes, salivation, weakness, and loss of weight lung irritation was noted at necropsy. A 2 4-hour exposure to 72 00 ppm caused light narcosis and delayed death due to pneumonia. Dogs exposed to 5000 ppm for 1 hour had nasal irritation and drowsiness. ... 

Intraperitoneal injection or oral administration to rats at doses that caused delayed death resulted in the same proliferative lesion in the lung findings were alveolar, perivascular, and peribronchial edema, with cellular proliferation into the alveolar walls resulting in large solid areas of the lung with no air-containing cavities. ... 

Four other dogs were treated with SOAz and cured in the same way. This brings real hope for the clinical treatment of osteosarcoma-bearing patients, especially as there is no chemotherapy available at all for such tumors and that surgery (amputation) is the only technique which might be able to delay death. Incidentally, it may be noted that 16,000 men and women died from osteosarcomas in 1980 in E.E.C. countries. . . ... 

The pump s major advantages are its ease of use and wide availability. Frequent lABP use is speculated to have been a factor affecting the low 30-day mortality of the medically treated group in the SHOCK (Should we emergently revascularize Occluded Coronaries for cardiogenic shocK ) trial [7]. However, other studies suggest that the lABP only delays death and does not prevent it [8]. The lABP s main limitations are its short duration of use and requirement for partially intact left ventricular function [9]. 

If an overdose of the local anesthetic has been taken by mouth, evacuation and chemical antidotes are indicated. If the anesthetic was injected, absorption should be blocked by ligation, if possible. Whatever delays death is likely to save the life in view of the rapid destruction of these drugs. If... 

A lead compound bearing a ferrocenyl moiety at position N(l) was identified. This derivative is more active than Ciprofloxacin and Doxycycline. The activity is remarkably constant regardless of the level of resistance to CQ of the strains. Contrary to other antibiotics, no delayed-death effect was noted. Isobologram analysis showed that this compound exerts an antagonist effect with the main quinoline-containing antimalarials. In vitro results have to be confirmed in vivo to check the bioavailability of the molecule and its potential interest as a new antimalarial [113],... 

Minimum acute lethal toxicity" for 3-d NA observation, 800-900 ppm. At 50-250 ppm, some delayed deaths occurred after the 3-d period. Al the higher concentrations, immediate effects included respiratory arrest and bronchoconstrictbn. After exposure ceased, gradual increase in respiratory rate for 1 h, subsided after 17 h. 

Almost no deaths occurred in Bhopal until 4 h after the MIC leak indeed, most deaths oeeurred between 24 and 48 h after the diseharge of the poisonous gas (Varma, 1986). This was followed by delayed deaths months and years after the aeeident (Varma and Mulay, 2006). This pattern of fatalities eharacterized by delayed and not immediate deaths in Bhopal (Varma, 1986) is mimicked by exposure of experimental animals to MIC (Boorman et ah, 1987 Bucher et al, 1987a, b Dodd et al, 1987 Fowler and Dodd, 1987a, b Stevens et al., 1987 Tepper et al., 1987 Uraih et al, 1987 Ferguson and Alarie, 1991). In contrast, at lethal concentrations, HCN would cause deaths almost immediately if deaths do not occur within 4 h, it is highly unlikely that they would occur at all. 

DOT CLASSIFICATION 5.1 Label Oxidizer SAFETY PROFILE Moderately toxic to humans and experimentally by ingestion. Mildly toxic experimentally by skin contact. Human systemic effects by ingestion ulceration or bleeding from stomach. A severe skin and eye irritant. Toxicity symptoms include emaciation, lethargy, weakness, and delayed death. Autopsy... 

Perez J, Burton BT, McGirr JG. Airway compromise and delayed death following attempted central vein injection of propylhexedrine. J Emerg Med 1994 12(6) 795-7. 

Delayed death occurred in animals after exposure to 150-200 ppm for less than 1 h. Rats repeatedly exposed to 10 ppm died after 10-13 days of exposure. Rats are more sensitive than mice to the... 

Guinea pigs exposed to 2.4% ethyl bromide in air for 30 min experienced some delayed deaths and pathological changes in lungs, liver, spleen, and kidneys. Ethyl bromide is a central nervous system (CNS) depressant causing pulmonary congestion, centrilobular necrosis of the liver, and diffuse nephritis. 

The fate of the subject is usually decided within the first half hour after ingestion and depends on the quantity of poison absorbed and the length of time between the poisoning and the beginning of therapy. In about 20% of dogs, a delayed death may occur in which brain lesions are noted (Haymaker et al., 1952). This is frequently observed in higher animals and probably in humans due to complications arising from the acute neural anoxia (Coon et al., 1943). 

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