Lethal effect

The lethal effects of cadmium are thought to be caused by free cadmium ions, that is, cadmium not bound to metallothioneins or other proteins. Free cadmium ions may inactivate various metal-dependent enzymes however, cadmium not bound to metallothionein may have the capacity to directly damage renal tubular membranes during uptake. 

Birds are comparatively resistant to the biocidal properties of cadmium. All the adult drake mallards (Anas platyrhynchos) fed up to 200.0 mg Cd/kg diet for 90 days survived with no loss of body weight. Laying hens fed 200.0 mg Cd/kg diet also survived egg production was suppressed at that concentration but not at lower concentrations tested. Marine and terrestrial animals, including ducks, have been shown to be particularly abundant in a wildlife community associated with a marine sewer outfall these animals were contaminated with 

---

TNE- a also protects mice against the lethal effects of radiation (164). TNE- a given before sublethal kradiation reduces the decline of neutrophils and total blood counts and accelerates the recovery of peripheral blood cells (190). TNE- a also alters the radiosensitivity of murine G1 progenitors (191). 

An acute lethal dose (LC q) for vapor exposure to 1,1,2-trichloroethane in the rat is 2000 ppm for a 4-h exposure. The same lethal effect occurs at 18,000 ppm vapor during 3 h exposure to 1,1,1-trichloroethane. The oral LD q for 1,1,2-trichloroethane in rats is 0.1—0.2 g/kg, classifying it as moderately toxic (109). Liver and kidney damage occurs at even lower dosages. Skin adsorption is a possible route of overexposure. 

Tetrodotoxin is one of the most powerful non-protein neurotoxins known. It occurs in the liver and ovaries of the Japanese puffer fish, Sphoerides rubripes and S. phyreus, and its lethal effects have been known for centuries, although it was isolated in crystalline form... 

Kulstad and Malmsten tested a number of derivatives of l,10-diaza-18-crown-6 (9) for toxicity in mice (intravenous). Compound 9 and the bis-N-2-hydroxyethyl,bis-N-2-carboxamidomethyl, and bis-N-2-carboxymethyl derivatives of 9 were tested and all were found to be toxic in the range of 5—50 mg/kg. At a dose level of 5 mg/kg of 9, the two mice tested were still alive after a week, but at a dose level of 25 mg/kg, the mice died in less than 24 h If these data could be translated directly to human beings, a 100 kg human would require something between 0.5—2.5 g of compound (i.v.) to produce a lethal effect. 

Most drugs can be expected to have potentially lethal effects, as their usefulness depends on their ability to infiuence physiological processes. However, the dose level at which toxic effects manifest should be significantly higher than those required to produce a pharmaceutical response, so that a good safety margin exists between therapeutic and toxic levels. 

Monooctyltin/ dioctyltin (contd) Rat DOT stabilizer mix (DOT(IOMA) MOT(IOMA) 80 20) Gestation days 6-15 at 0, 1,5, and 25 mg/kg body weight Marginal maternal toxicity marginal but significant embryo-fetal lethal effect LOAEL = 25 NOAEL = 5 Sobering AG (1991)... 

In rats, exposed males and females appear to have different sensitivities to the lethal effects of endosulfan exposure. Summary data submitted by Hoechst (1990) showed that female LDjg values ranged between 10 and 23 mg/kg, whereas male LDjo values ranged between 40 and 125 mg/kg. Thus, female rats appear to be 4-5 times more sensitive to the lethal effects of technical-grade endosulfan than male rats. This difference may be related to differences in the toxicokinetics of endosulfan in male and female rats (see also Section 2.3). Insufficient data were available to determine whether differences in sensitivity to lethal effects exist between males and females of species other than the rat. 

The effects of protein deficiency on endosulfan toxicity were studied in Wistar rats (Boyd and Dobos 1969 Boyd et al. 1970). Rats fed a diet totally deficient in protein for 28 days prior to administration of a single oral dose of endosulfan had an LDjq of 5.1 mg/kg of endosulfan. Rats fed a low-protein diet (3.5% protein) for 28 days had an LDjq of 24 mg/kg of endosulfan. Rats fed standard laboratory chow (26% protein) had an LDjq of 102-121 mg/kg. The immediate cause of death in all animals was respiratory failure following tonic-clonic convulsions. This study demonstrated that, while a protein-deficient diet does not affect the nature of the toxic reaction, it may affect the sensitivity of rats to the lethal effects of endosulfan. 

Although the specific cause of death was not discussed in the Hack et al. (1995) study, it does not appear that neurological effects played any role. Mice generally appear to be more sensitive to the lethal effects of endosulfan than rats (Gupta 1976 Gupta et al. 1981). Female rats are more sensitive to the lethal effects of endosulfan than male rats (Gupta 1976 Hoechst 1990). 

Protein deficiency enhances the lethal effects of endosulfan in Wistar rats (Boyd and Dobos 1969 Boyd et al. 1970). Thus, humans consuming protein-deficient diets may represent a sensitive subpopulation (see Section 2.9). 

Neurotoxic compounds can have behavioral effects in the field (see Chapters 5, 9, and 15), and these may reduce the breeding or feeding snccess of animals and their ability to avoid predation. A number of the examples that follow are of sub-lethal effects of pollutants. The occurrence of sublethal effects in natural populations is intimately connected with the question of persistence. Chemicals with long biological half-lives present a particular risk. The maintenance of substantial levels in individuals, and along food chains, over long periods of time maximizes the risk of sublethal effects. Risks are less with less persistent compounds, which are rapidly... 

Tamplin et. al. (54) observed that V. cholerae and A. hydrophila cell extracts contained substances with TTX-like biological activity in tissue culture assay, counteracting the lethal effect of veratridine on ouabain-treated mouse neuroblastoma cells. Concentrations of TTX-like activity ranged from 5 to 100 ng/L of culture when compared to standard TTX. The same bacterial extracts also displaced radiolabelled STX from rat brain membrane sodium channel receptors and inhibited the compound action potential of frog sciatic nerve. However, the same extracts did not show TTX-like blocking events of sodium current when applied to rat sarcolemmal sodium channels in planar lipid bilayers. 

The LD p of pal oxin in female Swiss Albino mice 24 hours following intra-peritoneal injection is 5 x 10 mg/kg (5). The immune sera also neutralized palytoxin s lethal effects. As shown in Figure 3, 11/12 mice were killed by palytoxin (1 X 10 mg/kg), whereas 0/12 and 0/11 mice were killed by palytoxin when injected intraperitoneally in the presence of the immune serum. None of the protected mice showed any signs of distress. 

This chapter is concerned therefore with studies of the mechanism of action of palytoxin, how it produces its lethal effects, as well as attempts to develop an antidote for this form of poisoning. 

Figure 2. Effect of treatment with isosorbide dinitrate in reversing the otherwise lethal effect of palytoxin. (Reproduced from Ref. 10.)...

Botulinum antitoxin Neutralizatien ef the lethal effects of botulinum toxins A, B and E in mice SOOlUmI- eftypeA 5001U mM ef Type B 50IU ml- ef Type E... 

---