chemical compounds were selected and tried out in military operations between 1915 and 1918. The majority of these substances were eventually discarded because the actual results obtained in the field failed to measure up to theoretical expectations. Yet the experience thus gained not only increased knowledge of the absolute toxicities of many chemical ««oinpounds, but also j>ermittcd the formulation of definite relations between the various factors entering into the problem, so that basic principles could be deduced and the whole subject established on a scientific foundation.
While the study of this field of toxicology has, since the war, engaged the attention of scientists generally, the interest and talent devoted to this subject in Germany continues to command respect. It is, therefore, Mieved that the German x-iewjKjint on toxicity of war gases deserves consideration and w'e accordingly follow with some freedom the presentations of German authorities in this field, notably those of Drs. Haber, Flury, Meyer and Buscher,
The effects of chemical agents upon the human organism result either from internal contact, as inhalation, or from external contact with various body surfaces. Chemicals such as dichlordiethvl sulfide (mustard gas) combine both of these types of effect. Yet the two must be approached independently before cumulative toxicity may be quantitatively determined.
Considering first those agents whose vapors when inhaled produce deleterious internal reactions, it is found that a definite relation exists between the concentration of vapor present in the air, the amount of such contaminated air that is admitted into the body, and the toxic effect produced upon the body. This relation has been established by Haber as follows:
Most toxic substances on contact with the. body react chemically with the living tissues and destroy them"by forming chemical combinations therewith. The degree of intoxication or poisonous effect is proportional to the chemical reaction of the toxic substance on the body tissues. This reaction is a function of three independent variables:
1. The time of exposure to the toxic substance.
2. The concentration of the toxic substance.
3. The concentration of Ihe living material (body tissues).
Let c = the concentration of the vapors or droplets of the toxic substance in the air, expressed in milligrams per cubic meter, v = volume of air breathed in, per minute, t = time of exposure to the contaminated atmosphere, in miuutcs,
G = weight of the body, in kilograms; then the quantity of poison inhaled and generally retained in the body would be 12
and the degree of intoxication or poisoning, /, is
Death occurs when the degree of intoxication, /, equals a constant
m 12p0C yoo £200 lipoo £100 2000 IQpOO
V?oo |L800 woo fcUOO I Ju>oo >aoco
Temperature «n Degrees C. Typical vapor pressure und volatility curve«
critical limit, W, which is specific for each kind of animal and for each loxic substance, i.e., when
In general, the amount of air inspired per minute is proportional to the body weight of the higher animals, so that the ratio v/G is constant. for a given species and may be written as unity for the purposes of comparing the toxicities of gases on the same kind of animals. Then et = W
l¿»ili:il Index 450 500 1,5<X> 1, fillO 2,000 2.000 3. IKK) 3,000 3,000 3,00(1
phenomenon it is necessary to insert an "elimination factor," e, in the Haber formula, which then reads
Here the relation between c and e demands a critical density of concentration below which systemic jkmsohs are noneffective, and the observed data confirm this result.
In accordance with these formulas, toxicity data arc experimentally determined by closely observing the physiological reactions? of test
animals under carefully controlled experimental conditions. While the effects on the higher animals arc not in all cases absolutely parallel with human reactions, they do furnish valuable relative toxicological data as between various chemical agenta. The following table presents lethal indices so computed for certain well-known chemical substances.
Kki.ativk Toxicity from Inhalation (After Uaber) I rmu-ntilde Reaction*
llcnxyl iodide 3,000
Mel hyldiehlorarsinc 3,000
Piphenylehlorarsine 4 ,000
Xylvl hronmle 0.000
Hromtonzyl cyanide 7.500
Hydrocyanic acid 1.000--4,000*
Carbon monoxide 70,000*
♦Tilt' lethal in«lico» of the »//Hemic poison« depend upon tlie <li'«m' of emu-en»™Hon e. mt.i the producl c X 11or iho«« cnmpouniU 1« lliercfwe nol rotwtnnt.
From the above table it appears that fatalities result from normal inhalation for 1 minute in an atmosphere contaminated with a concentration of 450 mg. of phosgene i>er cubic meter of air. The deadliiwss of agents of the phosgene tyj>e is further emphasized by tlx* fart that they may be equally effective in smaller quantities when inhaled over longer periods, which does not hold true with the systemic toxics, such as hydrocyanic acid and carlxm monoxide. In the ease of phosgene, the absolute quantity of vapor required to produce death (toxicity index 450) is about 3.6 mg., based on a normal inspiration of 8 liters of air per minute, or 8 X 45<Kooo = 3.0. Generally speaking this quantity of phosgene vapor introduced into the lungs will, as Flury (5) indicates, cause death even when inspired more slowly in a concentration corre-
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