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154 FRANK A. PATTY concentration of a gas that will dissolve in a liquid is directly proportional to itsi' concentration in the free space above the liquid, may be expressed as C1/C2 -- Ky where C1 and C2 are the molar concentrations of the gas in the liquid and vapor| phases, respectively, and K is the solubility coefficient. This coefficient is different^ for each vapor, each liquid, and each temperature. Henderson and Haggard1 have proposed that this law be expressed in a more.' convenient form when applied to the absorption of gases through the lungs into the? blood. They suggest C/Ci = D, where D is the coefficient of distribution, C is.thej* concentration in the fluid phase (blood), and Ci is the concentration in the vapor* phase in alveolar air, both concentrations to be expressed on a weight per volumi basis (milligrams per liter). This form of the law is particularly convenient for the;` purpose intended, and it is to be hoped that additional data will be collected tti|, establish the coefficient of distribution of more gases and vapors between the at* mosphere and the circulating blood. For a miscible or highly soluble material the' coefficient of distribution cannot be approximated by calculation, but for a less) TABLE 1 Distribution Coefficients Solvent Methyl alcohol Ethyl alcohol Isoamyl alcohol Primary n-amyl alcohol Secondary isoamyl alcohol. Acetone Methyl n-propyl ketone Diethyl ketone Methyl isopropyl ketone Ethyl ether Benzene ' Carbon disulfide Coefficient of distribution" 1700' 1300 836 804 ............ ..... . .550.________ _______ 330 167 157 101 15 6.58" 6 * The coefficient of distribution here is the ratio of milligrams of solvent per liter of blood' to milligrams of solvent per liter of alveolar air. * Based upon room air rather than alveolar air. readily soluble vapor it can be approximated from its vapor pressure and solubility St'b'^^tTmpilatJip^^^CrTKecoefficientdfdisffiBufion islc^Sf^aFforthe ,am" vappr and iiqyia,a>t any given temperature regardless of.the concentration of vapor in the atmosphere. ' The coefficient is known for the solubility of relatively few vapors and gases iS- blood at body- temperaturej-this'being a field that has beeminsufficiently exploit" * H. W. Haggard, D. P. Miller, and L. A. Greenberg, J. Ind. Hyg. Toxicol., 27, 1 (1945).'?f * A. P. Briggs and P. A. Schaffer, J. Biol. Chem, 48, 413 .(1921). ($? *H. H. Schrenk, W, P. Yant, S. J. Pearce, F. A. Patty, and R. R. Sayers, J. Ind. Hygt Toxicol., 23, 20 (1941). Ssearns Sfi'Vvr; f ENTRY AND ACTION OF TOXIC MATERIALS 155 sffiTOxreity.-studies. It is to be hoped that in the future-such studies will include the i^^^natfihl'pressure of the vapor or gas under observation in alveolar air, and in the y^SliSciytflu ids,;>at time intervals during accumulation and elimination of vapors, as equilibrium. In computing a coefficient of distribution from room-air p <^?r('c01'?entrat'on da*a> corrections for changes in temperature and partial pres^surwoffwiuer vapor should be made if comparisons are desired with coefficients {jj^lV'lj.u 0011 .alveolar air, because alveolar air approaches saturation with water %u^hiS70 C. (47 mm. Hg partial pressure). Some of the coefficients that have S'e^^tpblished are given in Table 1. s ,' S. Body Saturation fflwsISsbsfv. Sfa'K^j'rpmitthe foregoing it is evident that any gas or vapor in the air we breathe ^0nfls''"(t'o: pass through the lungs into the blood stream and to be distributed ^p^Mghout.Hthe body. The respiratory tissue in the lungs, which has been esti- ^^^^^tOjhave a surface area of about 55 sq. meters, acts as the exchange surface rj^|i-c\}S|i5od and air. The blood in the capillaries is said to be separated from the the alveoli by two membranes of the utmost delicacy, perhaps only one cell jp^cI|s,`iS0 it becomes evident that equilibrium between the blood in the lungs g^P^gf|$olar air is reached rapidly. The accumulation of the foreign gas or he'body depends upon a number of factors: concentration in the air, the ip|fithe material in the blood and tissues, the length of exposure, the rate hing, the rate of circulation, whether the material is reactive, and others, tfgasfis verysoliiEle IHTfie'BldodTsatufation of the body is slow (requiring TjSrgely dependent upon the ventilation of the lungs, and is only slightly Rpiby changes in circulation; whereas with a very slightly soluble gas, such genfsaturation is very rapid (being nearly complete within a few minutes), IffllaSfendent upon the rate of circulation, and is little influenced by the rate jH^Wfith gases and vapors that are freely soluble in water and nonreacj|!||y|8lowly reactive, in the body, such as acetohe.and methanol, the ab- g*d|distribution throughout the body are dependent upon the water con` tfptiissues. Although the fat-soluble vapors may be transported chiefly Sueous content of the blood, they tend to concentrate in the fatty fflLimv. nonreactive vapors, although the blood, .and tissue concentra- io^^qffl'ibfiuS57STe^fop0ftiohal to the vapor'cbnceiitfation' and funcJlfeime of exposure, the rate of saturation is, with constant circulation mingy,a relation peculiar to each vapor and independent,of,the concentrahe-||gpr. In other words, the same time is required for tfte'same vapor to ^giv^^rcentage^saturation-of`the body; regardless of the concentration of " pni^tfie atmosphere breathed. 3'!^t||||ctical to speak of the exact time required for complete saturation, t^K^dnable and too indefinite. It is, however, practical to state a time ^of cntage saturation such as 50, 60, 70, 80, or even 90 per cent of saturation, SST'' 1 JSftfe-..