Sublethal

Toxicity. Lethality is the primary ha2ard of phosphine exposure. Phosphine may be fatal if inhaled, swallowed, or absorbed through skin. AH phosphine-related effects seen at sublethal inhalation exposure concentrations are relatively small and completely reversible. The symptoms of sublethal phosphine inhalation exposure include headache, weakness, fatigue, di22iness, and tightness of the chest. Convulsions may be observed prior to death in response to high levels of phosphine inhalation. Some data are given in Table 2. 

One vitamin E analogue, TROLOX, inhibits radiation-induced apoptosis in murine thymocytes (26). Chicks given vitamin E prior to exposure to a sublethal dose (2.25 Gy (225 rad)) of y-radiation demonstrate a more rapid recovery from damage to the thymus (100). 

The effects of lL-1 ki accelerating recovery of BM hemopoiesis ki mice have been characterized (172). Injection of lL-1 20 h prior to sublethal kradiation promotes an eadier CEU-S/CEU-GM recovery ki the BM and spleen, and markedly affects BM ceUularity and mobilization of progenitor cells (172). Differences have been found between strains and administration protocols, especially with respect to BM CEU-GM numbers. 

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). 

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. 

A concentration of 35,000 ppm in air produces unconsciousness in 30—40 minutes. This concentration also constitutes a serious fire and explosion hazard, and should not be permitted to exist under any circumstance. Any person exposed to ethyl ether vapor of any appreciable concentration should be prompdy removed from the area. Recovery from exposure to sublethal concentrations is rapid and generally complete. Except in emergencies, and then only with appropriate protective equipment, no one should enter an area containing ether vapor until the concentration has been found safe by measurement with a combustible-gas indicator. 

Toxicity. A 1% concn of the gas in air is lethal to rats in 1 hour, its effect being similar to C monoxide the LD50 in rats when injected intra-peritoneally is 8.2ml/kg (Ref 16). Earlier workers assumed that the toxicity of N trifluoride would be similar to H fluoride and that the latter would be formed by hydrolysis in body tissues (Ref 1). This has recently been shown to be erroneous, and that it is stable under physiological conds. The toxic effect is due to its ability to complex with the hemoglobin of the blood causing anoxia. This effect is reversible, and animals receiving a sublethal dose recover rapidly upon removal from contact with N trifluoride (Ref 14)... 

Pope CN, Chakraborti TK. 1992. Dose-related inhibition of brain and plasma cholinesterase in neonatal and adult rats following sublethal organophosphate exposures. Toxicology 73 35-43. 

Diarrhea was observed in rats exposed for 5 days, 6 hours/day to both lethal and sublethal doses of P-endosulfan ( 250 mg/kg/day for males and i6 mg/kg/day for females) (Hoechst 1989b). Autopsy of animals from this study revealed that the mesenteric blood vessels of one of the surviving females exposed to 16 mg/kg/day were distended with blood, and that the small intestines of animals dying as a result of exposure were filled with a reddish fluid (500 mg/kg/day for males and 31.25 for mg/kg/day females). In contrast, no treatment-related effects were revealed by routine gross and histopathological examination of gastrointestinal tissues (stomach, small and large intestines, and pancreas) from rats exposed to doses of 27 mg/kg/day (females) and 81 mg/kg/day (males) for 30 days, 6 hours/day,... 

Novak B, Ahmad N. 1989. Residues in fish exposed to sublethal doses of endosulfan and fish collected from cotton growing area. J Environ Sci Health B24 97-109. 

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... 

From an ecotoxicological point of view, it has often been suspected that sublethal effects, such as those described here, can be more important than lethal ones. Both p,p -DDT and p,p -DDD are persistent neurotoxins, and may very well have caused behavioral effects in the field. This issue was not resolved when DDT was widely used, and remains a matter for speculation. More is known, however, about eggshell thinning caused by p,p -DDE and its effects upon reproduction, which will be discussed in Section 5.2.5.I. 

FIGURE 5.6 Dieldrin intoxication in hnmans and its relationship to blood levels. The hatched area represents the sublethal effects seen at 15-30% of lethal threshold concentration in blood (after Jager 1970). 

Experimental animals exposed to sublethal doses of cyclodienes show a similar picture, with changes in EEG patterns, disorientation, loss of muscular coordination and vomiting, as well as convulsions, the latter becoming more severe with increasing doses (Hayes and Laws 1991). It is clear from these wide-ranging studies that a number of neurotoxic effects can be caused by cyclodienes at levels well below those that are lethal. In the human studies described here, subclinical symptoms were frequently reported when dieldrin blood levels were in the range 50-100 pg/L, an order of magnitude below those associated with lethal intoxication. 

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