Thirty‐six alkyl organophosphorus compounds have been tested for neurotoxicity in the chicken. The individual compounds were chosen to enable the importance of each portion of the molecule to be assessed in relation to the property of neurotoxicity. Seventeen substances were found to be neurotoxic, fifteen for the first time. All of these contained fluorine. On the basis of the results reported, certain predictions have been made about the chemical structure of compounds which would be expected to be neurotoxic. The importance of fluorine suggests that it plays a direct role in the development of the biochemical lesion, and this may occur as the result of its being carried by the molecule as a whole to specific areas in the nervous system. By the action of cholinesterase, the P‐F bond may be ruptured and ionic fluorine liberated where it blocks some metabolic cycle.
In so far as the toxic effects of a lethal inhalant depend upon the amount of material absorbed these effects must depend upon the dosage (Ct) to which animals are exposed, where C=the concentration of the gas in mg. per cubic metre and t =the time of exposure in minutes. It must also depend upon the rate of inhalation and the efficiency of absorption of the gas in the respiratory tract. The present experiments show quantitatively how the median lethal dose of phosgene expressed as the L(Ct)50 varies with the exposure time (t). From the data it is possible to deduce the probable extent to which different species reduce their breathing rate in an irritant gas.The expression for toxicity or lethal index (L) advanced by Haber (cf. Prentiss, 1937) was L=CtvG .(1) where C=concentration of toxic substance, t=time of exposure, v=volume of air breathed in per minute, and G =body weight in Kg. In general, for any one species under the same conditions vIG is constant, so that for any one species Ct would be constant. Thus the lethal index, or the median lethal dose, L(Ct)50, should be constant for any one species if the breathing rate is unchanged. American work on the toxicity of phosgene for dogs (Geiling, 1944;Prentiss, 1937) showed that the "lethal index " rose from 4,500 mg. min./m.3 when t was 2 min. to 12,000 mg. min./m.3 when the exposure time was 75 min. This increase in the lethal dose with increase in exposure time can be corrected for on the assumption that the organism can eliminate a constant amount of the toxic agent. By introducing an elimination factor C0 which may be assumed to be equal to the just harmless concentration, the formula becomes
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