684
INDUSTRIAL AND ENGINEERING CHEMISTRY
(consequently DF = Q B ) . Extend line A F until it intersects line ED a t G. C H , the horizontal coordinate of point G, equals P A . (The above applies also for S A > S B ) . Triangles FGH and A C F are similar; therefore, GH
AC
FH
GH
=mor-=
CH -
SA
GH= _D H _ CE cD
or-=SB
GH
- SA
&A
&A
1
- CH
(16)
1
Combining Equations 15 and 16 by eliminating GH, and solving for C H ,
Vol. 34, No. 6
Since in most cases the significant figures for compositions go t o only about four places, a graph paper about 50 X 60 cm. in size will ensure accuracy equal to numerical calculations. If an ordinary graph paper (8.5 X 11 inches) is used, the accuracy equals that of the slide rule. These methods have been applied to actual problems and found to require less than half the time necessary to carry out the conversion by slide-rule calculation. Because of their simplicity these graphical methods introduce less error than numerical calculation. Although only parts by weight have been considered in method I, it is obvious that parts by volume or numbers of moles can be treated similarly if desired.
Nomenclature molecular weight p = density W = weight fraction V = volume fraction X = mole fraction M
=
..-.~---
T i = run n r t hv woivht Ir' I
The same example as in method I is used and the graphical solution is shown in Figure 3, from which we find
Aclrnowledgmen t
A C = Msio, = 60.06 ( S A ) A E = M K ~ O= 94.19 Sa) CF = wsio, = 0.70 LA,
with the following result: Xsion = CH
= 0.786
Q = a quantity which may be W , V, X , or U S = a uantity which may be 114, p (Mlp),( p / M ) , or unity P = a fraction which may be W , $, or X Subscripts A and B = components A and B, respectively, in binary system A-B
The application of method I by Tong Yee in an actual problem led the writers to the development of method 11. They are indebted t o Tong Yee.
(PA)
Literature Cited
The method of finding P i of Equation 11 will be similar.
Discussion Although method I offers wider scope of application, method I1 is preferable when many conversions of a given type are t o be carried out simultaneously.
(1) Baker, J. S., Chem. & Met. Eng., 45, 155 (1938). (2) Bridger, G.L.,Ibid.,44,451 (1937). (3) Byerlv. W.. J. Chem. Education,18,465 (1941). (4) Nevi& H.G.,Chem. & M e t . Eng., 39, 673-5 (1932). (5) Patton. T.C.,Ibid.,41, 148-9 (1934). (6) Underwood, A.J. V., Trans.Inst. Chem. E ~ Q T 10,112-52 s., (1932) I
CONTRIBUTION 447 from the Department of Chemistry, University of Pittaburgh.
CHRONIC TOXICITY OF DERRIS ANTHONY 8%.AMBROSE', FLOYD DEEDS, AND JAMES B. MCNAUGHT
Food Research Division, Bureau of Agricultural Chemistry and Engineering, U. S. Department of Agriculture, and the Departments of Pharmacology and of Pathology, Stanford University School of Medicine, San Francisco, Calif.
I
N THE search for effectivesubstitutes for lead arsenate and fluorine compounds as insecticides, the investigation of potential health hazards traceable to spray residues is an essential and indispensable part of the program. The determination of possible health hazards is especially important in the case of substitutes which show promise and are likely to find widespread use. I n view of the promising results being obtained with derris as an insecticide, the toxicity data of Haag (6) and Ambrose and Haag ( I , 8, 3) are important, and the additional data obtained recently in this laboratory should be of interest. The literature on derris was reviewed in the earlier papers by Haag and Ambrose. Haag (6) reported the acute toxicity, in terms of the minimal lethal dose, of rotenone by 1 Present
KY.
addrese, Univeraity of Louisville Sohool of Medicine, Louiaville,
various routes of administration in guinea pigs, rabbits, dogs, cats, pigeons, frogs, and albino rats, and presented data on the chronic toxicity, over a limited period of time, to dogs, rabbits, and guinea pigs. Ambrose and Haag ( I ) reported: the acute toxicity of whole derris administered gastrically to rabbits, rats, guinea pigs, and dogs; the acute toxicity of aqueous extracts of derris given gastrically to rats and rabbits, and intravenously+ intramuscularly, and subcutaneously to rabbits; the acute toxicity of the acetone soluble fraction of derris; the lethal dose of an olive oil extract of derris given gastrically to rats and rabbits; and the irritant properties of derris applied l,ocally, and its anesthetic effects on nerve tissue and the mucous membranes of the mouth. Ambrose and Haag (2) also presented data on the comparative toxicities in rabbits, rats, and guinea pigs of rotenone, deguelin, toxicarol, dehydrorotenone, and dihy-
INDUSTRIAL A N D ENGINEERING CHEMISTRY
June, 1942
Existing data on the acute and chronic toxicity of derris are summarized. The study of the chronic toxicity of derris is extended to include a different strain of albino rats maintained on a different basic diet from that formerly used. The quantity of total extractives and the qualitative and quantitative composition of the extractives are more important factors in the chronic toxicity of derris samples than is the rotenone content. Evidence of liver injury has been found in albino rats receiving daily in the diet a concentration of derris or cube corresponding to 75 parts per million parts of diet. Variations in composition of derris and cub6 necessitate caution in making sweeping generalizations regarding the toxic properties of derris and cub6 on the basis of studies on a few samples.
685
One hundred and two healthy albino male rats were used for the results of feeding shown graphically in Figures 2 and 3,re resenting an average period of 115 days. These rats varief in weight from 31 to 62 grams, average 48.5 grams. They were divided into seventeen groups of six rats each and were so distributed that the average weight of the animals in a group ranged from a minimum of 40.3 to a maximum of 56.3 grams. Two of the groups, or twelve rats, served as controls. Concentrations of 0.06 0.09, or 0.12 per cent of each of the five derris samples which had passed through a 100-mesh sieve were mixed with the basic diet and fed to the remaining 15 groups of rats. The basic diet had the following percenta e composition: corn meal, 73.0; linseed oil cake meal, 10.0; alfaha] 2.0; casein, 10.0; sardine oil, 3.0; bone ash, 1.5; sodium chloride, 0.5. Other groups of rats were placed on diets containin 0.0075,0.015, 0.03, and 0.24 per cent of the various derris sam,”ies. These latter groups will not be discussed in regard to growth rate except t o state that they grew normally on the three lowest doses and failed to survive on diets containing 0.24 per cent derris. In still another experiment a portion of derris sample I. D. 3006, containing 3.6 per cent rotenone and 15.6 per cent carbon tetrachloride extractives, was thoroughly extracted with acetone in a Soxhlet extractor. The dry residue was incorporated in the basic diet in a concentration of 1.2 per cent and fed t o a rou of five male rats for 154 days. In all cases the rats were p?aceX in cages provided with water bottles and food cups, designed to reduce losses t o a minimum and permit free access to food and water a t all times. The rats were weighed on an average of twice weekly and the food intake was recorded.
drorotenone, and the results (3) of continued feeding of a single sample of derris to rabbits, dogs, and albino rats.
Present Studies The transfer of one of the authors (Ambrose) from the laboratory a t Richmond, Va., to the laboratory at San Francisco, Calif., presented an opportunity to extend the investigation of derris to a different strain of albino rats, maintained on a different basic diet and kept under different laboratory conditions. Aside from these differences in experimental conditions, two other points have received partiular attention in this study. First, emphasis has been placed on continued feeding of derris, and secondly, five different samples of derris have been used. (The term “derris” is used here and in Figure 2 to include both derris and cub&) These derris samples varied in rotenone content from 0.6 to 9.6 per cent. Since rotenone is the best known of the derris constituents and bioassays of derris are frequently based on a rotenone standard, it was hoped that the continued feeding of samples of derris of different rotenone content might determine whether the chronic toxicity of derris bears any relation to the rotenone content. Additional information on this point was obtained by continued feeding of albino rats which received various concentrations of pure rotenone added to the basic diet. The samples of derris were supplied by the United States Bureau of Entomology and Plant Quarantine, and had the composition given in Table I. TABLEI. COMPOSITION OF CUBBAND DERRISSAMPLES CC14 Ext.* % Benzene Ratio Rotenone/ Sample, No. Rotenone, % No. 10 No. 2 Ext., % T o t h Ext., % 3004 2.9 17.69 16 16.5 18 0.6 12.8 6 3007 3006 3.6 16.8 15.6 15.7 23 3001 5.2 14.46 14.3 14.8 36 2221 9.6 23.3 28.6. 33.7 The values for total carbon tetrachloride extractives (oolumn 1) were determined by J. 0. Thomas of this laboratory. All other data were obtained from the re ort b y Jones and Graham (10) or personal oommunioations from R. C. R o d , Inseoticide Division, Bureau of Entomology and Plant Quarantine.
I. D.
{:$::)
..
..
DOyS
35
70
105
140
I
5
FIGURE1. EFFECTOP CONTINUED INGESTION OF DERRIS MARC ON GROWTH Cmtms OB RATS
Rats surviving on these diets for an average period of 200 days were autopsied and examined for gross changes, and sections of organs were made for histological study. Because of the importance attached to the rotenone content of cub6 and derris, a group of thirty rats was used to determine the effect of pure rotenone added to the basic diet. These rats were males weaned at 28 days of age, and were divided into five equal roups one of which served as control. Four groups received the fasic diet to which had been added 0.009, 0.01, 0.015,and 0.02 per cent of rotenone.
Interpretation of Results The growth curve of rats receiving a diet containing 1.2 per cent of the acetone-extracted marc (Figure 1) closely paralleled the growth curve of the control rats during the first 70 days, and even at the end of 154 days the difference in average weights of the two groups was only 14 grams. Therefore, it seems evident that acetone had extracted all
686
INDUSTRIAL AND ENGINEERING CHEMISTRY
the toxic principles capable of retarding the growth of albino rats. In view of the report by Ginsburg and Granett (6) that such an extracted marc still had insecticidal activity, it may be worth while to investigate the marc for the presence and isolation of the substance or substances having insecticidal action and possessing such low chronic toxicity for rats.
Effect On
-
DERRIS Of
Albino
G O * '
Rats
0 . '
I
'
Diets
Contoin
S a m p l e ~o
I Derris
I.D. 3001
( 5 . 2 % Rotenonel
25 Days on
Diet
We may now consider the growth curve for sample I. D. 3004 which obviously does not fit into the interpretation of Figure 3 given above. As pointed out above, the term "derris" has been used to include both derris and cub6. Sample I. D. 3004 with a rotenone content of 2.9 per cent was derived from cub6 root and not from derris. Figure 3 shows that a level of 0.06 per cent of this sample in the diet permitted as good growth as in the controls. The rate of growth on 0.09 per cent was only slightly poorer than that of the controls, and on 0.12 per cent was still better than that of rats receiving the same concentration of sample I. D. 3007 which contained 0.6 per cent rotenone. This lower toxicity of cub6 sample I. D. 3004 cannot be explained by the amount of carbon tetrachloride extractives because Table I shows that this sample contained more such extractives than did samples I. D. 3006 and 3001 These resu!ts indicate that, while the toxicity of derris may bear a slight relation to the rotenone content, the carbon tetrachloride extractives also play a role in the toxicity, and that in the case of this sample of cub6 there was lacking in the extractives some substance or substances which contributed t o the toxicity of derris. Discussion as to the cause of the decreased growth rates indicated in Figures 2 and 3 must take into consideration the rotenone content, the total extractive content together with its qualitative and quantitative composition, and the possibility of decreased food consumption. As already pointed out, the growth curves and rotenone content of the various derris samples suggest that the deleterious effect on growth tends t o increase with the rotenone content but that the magnitude of the effect may not be statistically significant. Since rotenone is a definite and crystallizable entity, the role of this constituent may be examined experimentally as shown below Evidence has been presented to show that the quantity of total extractives has an effect on growth rate, and that the qualitative and quantitative composition of the extractives may be equally important. The exact role played by the extractives cannot be tested experimentally because complete qualitative and quantitative data on the extractives are not available. Moreover, the information which is available in published reports, such as that of Jones (8),on the colorimetric evaluation of derris and cub6 reveals such wide variations in composition that toxicity data on the total extractives would be of little practical value. The data would of necessity apply only to the derris samples in question and could not be made the basis for a generalization on the toxicity of total extractives. The relation of food consumption t o retarded growth is subject to experimental study, and this factor is considered below. The rotenone content of the various samples studied is given in Table I. Determination of the concentrations of pure rotenone to be added to the basic diet, to produce various degrees of growth inhibition, together with data on food intake, furnish information as to the role played by rotenone in the growth rates when various derris samples are incorporated in the basic diet, The results of such an experiment are presented graphically in Figure 4. The rats receiving 0.009, 0.01, 0.015, and 0.02 per cent rotenone in the diet had average food intakes per rat per day of 11.34, 8.82, 8.36, and 8.52 grams, respectively, corresponding to rotenone intakes of 1.0, 0.88, 1.25, and 1.7 mg. per rat per day. These values are best compared with the rotenone intake per rat per day for derris sample 2221 which had the highest rotenone content, and on a dosage level of 0.12 per cent derris in the basic diet produced the most marked inhibition of growth. Rats eating this derriscontaining diet had an average food consumption of 7.2 grams per rat per day, corresponding t o an average daily intake of 0.83 mg. of rotenone per rat. At the end of 107 days rats
-+/' T
of Growth
50
75
100
1:
FIGURE2. EFFECTOF CONTINUED INGESTION OF DERRIS SAMPLE I. D. 3001 ON GROWTH CURVES OF RATS Derris sample I. D. 3001 contained 5.2 per cent rotenone and may therefore be regarded as a representative of the average derris available for insecticidal purposes. This is a t least true so far as the rotenone content is concerned, and since the potency of a given derris sample is determined by the goldfish method of bioassay which, in turn, is based upon a rotenone standard, we may assume for the present that the rotenone content is the most important factor. Figure 2 presents the growth curves of control rats and of those receiving 0.06, 0.09, and 0.12 per cent of this derris sample in the diet. As stated previously, concentrations of 0.03 per cent or less had no effect on growth, but Figure 2 shows a definite and increasing retardation of growth on 0.06 per cent and higher. Figure 3 presents the effects on growth rate produced by diets containing 0.06, 0.09, and 0.12 per cent of derris. For each dosage level, the growth curves of the five different derris samples are represented by characteristic lines. If consideration of the growth curve for sample I. D. 3004 is omitted for the present, it is seen that, on a given level of derris in the diet, the deleterious effect on growth rate appears to increase with the rotenone content of the derris sample. Also, this probable effect tends to increase with an increase in the percentage of derris in the diet. Certainly the curve for sample I. D. 3007, which contains the least rotenone, deviates more and more from the other curves as the dosage increases. However, although the other three curves bear the proper relation to one another, they are too close together t o warrant a conclusion of statistical significance.
Vol. 34, No. 6
INDUSTRIAL AND ENGINEERING CHEMISTRY
June, 1942
FIGURE3. EFFECTOF THREE CONCENTRATIONS OF VARIOUS DERRIS SAMPLESON GROWTH CURVESOF RATS
300 E f f e c t of on
50
p-
I
I
I
I
I
50
75
100
125
0.09 %
Growth
DERRIS
af
-----
Derris Sample No
"
. e
-..0
I
I
25
50
300t-
0
I
I
I
25 Effect of
on
of
I
'A
0
0.06 % DERRIS
Growth
25
Days
on
50 Diet
687
3007
"
"
"
04
Joo6
"
"
*'
300,
"
('
"
28.21
3004
I
75
100
125
I
I
I
75
100
125
receiving this amount of rotenone in the form of derris sample 2221 had an average weight of 188 grams as compared with an average weight of 295 grams for the controls. The average weight of the control rats a t the end of 107 days was 278 grams, whereas the rats receiving 1.0, 0.88, 1.25, and 1.70 mg. of rotenone per rat daily weighed 270, 220, 190, and 219 grams, respectively (Figure 4). Briefly, we may compare the rats receiving 0.83 mg. of rotenone daily in the form of derris with those receiving 1.7 mg. of pure rotenone daily. The former weighed 107 grams less than their controls, while the latter weighed only 59 grams less than their controls. Moreover, the decrease in food intake of the latter group was less marked. It is therefore evident that, while pure rotenone retards growth rate largely because of a decreased food consumption, the diminished growth of rats receiving derris must be attributed largely to factors other than rotenone. Since the quantitative and qualitative composition of the extractives in relation to growth cannot be investigated, we must be content with an examination of the data on food intake, realizing that variations in food intake may reflect variations in the composition of the extractives. The relation of food intake to growth rate may be shown in two ways. The food intake may be compared with the growth rate of rats receiving various concentrations of a given sample of derris, and it may be compared with the growth rates of rats receiving different samples of derris at a given dosage level. Figure 2 shows the growth rates of animals receiving the basic diet and three dosages of derris sample I. D. 3001 containing 5.2 per cent rotenone and 14.8 per cent extractives. The average daily food intake per rat for the controls was 14.59 grams. The rats receiving 0.06, 0.09, and 0.12 per cent of derris had average daily food intakes per rat of 14.3, 11.3, and 9.9 grams, respectively. These decrements in food consumption are believed to be largely responsible for the corresponding alterations in growth rates. Figure 3 (center) shows the growth rates of animals receiving the basic diet, and the same diet to which various samples of derris were added in a concentration of 0.09 per cent. This concentration was selected for making the comparison between food intake and growth rate because of the desirability of making the comparison a t the highest possible dosage level. Unfortunately the level of 0.12 per cent could not be used because food losses in some instances prevented accurate record of food intake. Sample I. D. 3004 (in reality a sample of cub&) caused only slight inhibition of growth, which is in agreement with the fact that the daily food intake per rat was 13.74 grams as compared with a control value of 14.59 grams. Derris samples I. D. 3007, 3006, 3001, and 2221 fed a t a level of 0.09 per cent of the diet permitted food intake values of 11.32, 12.06, 11.30, and 8.06 grams per rat per day. The decrements in food consumption are approximately parallel to the changes in growth rates. It was pointed out earlier in this report that cub6 sample I. D. 3004 was less toxic, as judged by growth curves, than any of the derris samples. This low toxicity was also r e vealed in the data on food consumption shown above. Since the total extractive content of the cub6 sample was 16.5 per cent, second only to that of derris sample I. D. 2221 which was 28.5 per cent, it is evident that food intake which governs
688
INDUSTRIAL AND ENGINEERING CHEMISTRY
growth to a large extent in these experiments reflects the variation in the quantitative and qualitative composition of the extractives. Jones (8) stated: “The ferric chloride test indicates from 1.5 to 2.8 per cent of toxicarol and sumatrol in the cub6 samples, although recently Rowaan and Van Duuren reported that they had been unable to find toxicarol in Lan-
ON GROWTH OF RATS FIGURE 4. EFFECTOF ROTEXONE
chocarpus (cub6) roots. The color may be due to other phenolic compounds.” Perhaps the lower toxicity of cub6 as compared with derris reported here is due to the absence of toxicarol. This is one possible example of an important qualitative and quantitative variation in composition of the extractives which may account for variation in toxicity as judged by growth curves.
Pathological Changes The histological studies of the tissues of all rats on the above diets showed essentially the same changes previously reported (3). The author (McNaught) who made the examinations of the tissues, had no knowledge of the composition of the various derris samples studied. His report follows: The adrenals, heart, kidneys, lungs, liver, stomach, small intestine, spleen, and testes from one hundred and twenty-four rats were examined microscopically by paraffin sections stained with hematoxylin and eosin. In addition, frozen sections of the kidneys, liver and adrenals stained with hematoxylin and Sudan I11 were exadined. There were no constant findings differing from the controls in any of the organs except the liver. In this organ, in the heavy concentrations of the various specimens, and diminishing but still in evidence in the lighter feedings, was a definite necrosis of the liver cells in the central and midzonal areas of the lobules. The cells were poorly outlined and granular, with many tiny fat droplets in the cytoplasm, and had faintly staining nuclei. In addition, there wa3 a slight increase in periportal lymphocytes and at times small collections of similar cells in the midzonal sinusoids. A mild congestion of the central veins and sinusoids was freauentlv noted. These liver changes - are indicative of abnormal metabolism and cell death. The livers of rats fed specimen I. D. 3007 definitely showed more marked changes than those fed the other specimens. The other specimens cannot be so readily arranged in their order of toxicity as judged by the liver damage, but the general impression is that samples I. D. 3006 and 3004 were quite simllar to each
Vol. 34, No. 6
other and produced slightly more damage than numbers I. D. 3001 and 2221.
Possible Public Health Hazards of Derris When the results of pathological examinations are viewed in the light of the chemical data in Table I , it is evident that chronic toxicity, as judged by liver damage, does not increase with an increase in content of rotenone and carbon tetrachloride extractives. I n fact, they suggest the reverse relation. I n the final interpretation of the significance of these studies of chronic toxicity of derris, one must keep in mind that evidence of liver damage is present in the lowest concentration fed-namely, 0.0075 per cent or 75 parts per million. At present we do not know holy small a concentration of derris in the diet would fail t o produce some evidence of liver injury in rats when fed over a period of time. Moreover, the rat apparently is the least susceptible, when compared with the dog and rabbit, as to retardation of growth and the dog is the most susceptible. The growth of puppies is retarded by a derris intake of 8.8 mg. per kg. of body weight per day (S), whereas approximately 120 mg. per kg. of body weight per day is required t o produce a comparable effect on the growth of rats. A similar relation holds for the amount of derris necessary to produce evidence of liver damage when fed continuously. Rmbrose and Haag (3) reported liver damage in dogs receiving 2.9 to 8 mg. per kg. of body weight per day. A concentration of 5 parts of derris per million of diet would therefore seem t o be a fair value on which to base predictions of the possible health hazards to humans. Haag and Taliaferro (7) studied the acute, subacute, and chronic toxicity of a single sample of cub6 containing 4.7 per cent rotenone and 19.69 per cent carbon tetrachloride extractives. The highest dosage used in continued feeding was 0.03 per cent (300 parts per million) and, like smaller concentrations, failed to inhibit growth. This observation agrees with the results obtained by lis. However, Haag and Taliaferro reported no evidence of tissue damage in either the chronic or the subacute experiments. Failure to find evidence of liver damage, as previously reported by Ambrose and Haag (S), in the subacute experiments may have been due t o the shortness of the time interval of 30 days. On the other hand, absence of liver damage in the subacute and chronic experiments may be due to a lack of toxicity in the particular sample of cub6 used. In other words, the report of Haag and Taliaferro on the absence of liver damage, may be in harmony with our results and the earlier results of Ambrose and Haag in so far as it points to variations in toxicity with different samples of derris and cube. The practical significance of these investigations in terms of possible public health hazards is, of courfie, the ultimate aim of the problem. The health hazards are twofold in naturethe possible injurious effects to workers engaged in grinding derris root and to those employed in applying derris sprays, and the possible existence of a spray residue hazard to the public consuming contaminated fruits and vegetables. The experiments on the acute effects of derris dusts (1) point to the presence of an industrial hazard to workers, but this objectionable feature may be overcome by adequate ventilation in grinding operations and by the use of suitable masks during both grinding and the application of sprays and dusts. The potential health hazards to the consuming public are much more difficult to appraise for three reasons, which prevent our carrying the interpretation beyond a statement of the facts: ( a ) Continued feeding of derris to rats in concentrations as low as 0.0075 per cent of the diet produces evidence of liver damage, and evidence is lacking to indicate how small a concentration is necessary before liver damage fails to appear; (b) there is a paucity of data on the chronic
INDUSTRIAL AND ENGINEERING CHEMISTRY
June, 1942
toxicity'of products in spray residues due to weathering of derris constituents; (c) the results of Fulton and Mason (4) show that derris is absorbed by plants from contaminated soil, and consequently the amount of derris in the spray residue may not be a true measure of the total derris consumed by the public. Experimental evidence (1, 9, 11) indicates that exposure t o the sun and atmosphere quickly causes derris to lose much of its insecticidal value and to suffer a marked decrease in its acute toxicity to mammals. However, it is not possible t o conclude that there would be a corresponding decrease in the chronic toxicity of derris after subjection t o weathering processes. It is therefore indicated that the effect of continued feeding of derris, after subjection to conditions analogous to weathering, must be studied before a final statement can be made on the possible health hazards of derris spray residues. Discussions as to the potential health hazards of chronic exposure to derris would be incomplete without an attempt to en phasize the complicated nature of the problem. Toxicity stuabs of a single chemical entity, or of a mixture of known compounds always occurring in known or fixed proportions, present relatively simple problems. Derris, cub6, and related materials, however, vary widely in composition, and there is reason to believe that not all constituents are known. The conclusions in this report pertain to the particular cub6 and derris samples investigated, and do not necessarily apply to any other sample. The observation that the cub6 sample
689
is somewhat less toxic than the derris samples cannot be interpreted to mean that all cub6 samples are less toxic than derris. The fact that a convenient bioassay method for rotenone exists and that derris may be blended to give a certain rotenone content (say 5 per cent) does not simplify the problem because uniformity in regard to other constituents would not be assured. The difficulty confronting the investigation of health hazards is analogous to an attempt to predict the therapeutic efficacy of a sample of digitalis leaves on the basis of a bioassay based on a single glucosidal constituent.
Literature Cited (1) Ambrose, A. M.,and Haag. H. B., IND.ENQ. CHEW.,28, 815 (1936). (2) Zbid., 29,429 (1937). (3) Zbid., 30,592 (1938). (4) Fulton, R. A.,and Mason, H. C., Science, 85, 264 (1937). (5) Ginsburg, J. M., and Granett, P., N. J. Agr. Expt. Sta., Bull. 576,16 (1934). (6) Haag, H. B., J. Phurmucol., 43, 193 (1931). (7) Haag, H. B.,and Taliaferro, I., Ibid., 69, 13 (1940). (8) Jones, H. A., IND. ENQ.CHEM.,ANAL. ED., 11, 429 (1939). (9) Jones, H. A., Gersdorff, W. A., Gooden, F. L., Campbell, F. L., and Sullivan, W. N., J. E m . Entomot., 26,451 (1933). (10) Jones, H.A., and Graham, J. J. T., IND. ENG. CHEM.,ANAL. ED., 10, I9 (1938). (11) Lean, P.A., van der, Indische Mercuur, 58, 257 (1935). CONTRIBUTION 45 from the Agrioultural Chemioal Research Diviaion, U. 8. Bureau of Agrioultural Chemistry and Engineering.
Molecular Refraction-Critical Temperature Nomograph D. S. DAVIS Wayne University, Detroit, Mich,
F
OR members of six important organic series Wan1 showed that the critical temperature is a linear function of the molecular refraction according to the equation: te
06 0 2
No.
-A-
t 2
+ Icz
=
and kl and kt depend upon the series as follows:
03
1
\
hR
critical temp. of the member, O C. R = mol. refraction of the member
where tc
\
Adds, orgat?& A/COhOlS
3 f5Jter.s 4 Ethers 5 Hydrocurbom 6 Nitriles
2 3 4 6
\
6
aeries Acids Aloohols Esters Ethers Hydrocarbons Nitriles
kr
ka
4.09 6.74 4.61 5.81 7.02 4.02
268.6 133.0 160.8 67.I 23.1 228.4
Critical temperatures can be read conveniently from the line coordinate chart by aligning the molecular refraction of a member with the series number and producing the line to the critical temperature scale. The dashed isopleth shows that ethyl propyl ether, which has a molecular refraction of 27.2 and belongs to series 4, has a critical temperature of 225' C. The observed value from International Critical Tables is 227.4' C. 1
Wan. 8.W., J . Phye. Chem., 45, 903 (1941).
