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The Specific Gravity Adjustment in Urinalysis Hervey B. Elkins, PhD, and Leonard D. Pagnotto, BS, Boston Over twenty years' experience with the specific gravity adjustment in urinalysis has been reviewed. It is concluded that this method of expressing results of analysis of urine for heavy metals, solvent metabolites, and radioactive isotopes is preferable to the unadjusted concentration. Complicating factors, which may affect the validity of specific gravity-adjusted values, include variations in diet and degree of sweating. The adjustment tails when applied to samples containing sugar. As between measurement of rate of excretion per 24 hours and the specific gravity adjustment, the latter is generally preferable for practical reasons. In extreme cases values obtained by the two methods vary by a factor of five or more. In such situations the best method of expressing findings is uncertain. In 1945 a paper entitled "Evaluation of Urinary Lead Determinations: I. The Significance of the Specific Gravity" ap peared in the Journal of Industrial Hygiene and Toxicology. The authors were Leo Lev ine and John P. Pahy,1 both chemists from this laboratory. In the paper the so-called specific gravity adjustment was proposed for recording the results of urinalysis for lead. Instead of reporting the findings as milli grams per liter, the following formula, in which the specific gravity of the urine sam ple is incorporated, was suggested: mg/liter (adjusted) => mg/liter (actual) x 1.024 sp gr -- 1.000 1.000 ' j i i I i i i y | 4. ? I | 's | | ^ Submitted for publication July 24, 1968; accepted Jan 8, 1969. From the Division of Occupational Hygiene, Mas- sachusetts Department of Labor and Industries, Bos- ton. Read before the annual meeting of the New Eng land Section ofAmerican Industrial Hygiene Asso- (nation, Framingham,Massachusetts, June 13, 1968. . Reprint requests to 39 Boylston St, Boston 0211G (Dr. Elkins). Arch Environ Health--Vol 18, June 19B9 i ; N36926 DUP05Q312882 'I i SPECIFIC GRAVITY IN URINALYSIS--ELKINS & PAGNOTTO 997 Table 1.--Effect 0/ Specific Gravity Reference Temperature Concentration of Contaminant Temp of Reference ! Sa mple, C Temp, C Sp G Actual Adjusted 25 25 1.006 0,05 0.20 25 4 1.003 0.05 0.40 The value 1.024 represented the mean spe study in which the results obtained with the cific gravity of the nearly 1,200 samples of specific gravity adjustment have been criti urine studied by Levine and Fahy. The cally compared with those using other adjusted volume of urine is given in liters, means of expressing urine concentration. as liteiSg or lg. As a result of this experience we have Adjusted volume = actual volume (liters) sp g -- 1.000 x 0024 = liters,.. been able to draw the following conclusions relative to the specific gravity adjustment, and specifically relative to the merits and implications of Levine and Fairy's paper: This was not the first time that the signif 1. The adjustment should not be limited t icance of the specific gravity of urine sam to analysis for lead. Levine and Fahy con ples' was discussed in this connection, but it fined themselves to this metal, probably be was the first proposal to include measure cause most of then data related to lead ment of this property as an integral part of analyses. Their reasoning would apply the analysis, and to make its determination, equally well to mercury, arsenic^ thallium, in some cases, as important as that of lead selenium, and fluoride, and probably metab ! i itself. olites of organic solvents. It would also be The paper attracted a fair amount of in applicable to most radioactive isotopes, but terest among laboratories which carried out these were of little importance at the rime of analyses of lead in urine, and a number Levine and Fahy's paper. It would also seem adopted the procedure which was advocated. logical to apply the adjustment in the quan Others rejected this method, however, some titative determination of coproporphyrin,Bii on the ground that it was an unnecessary amino-levulinic add and other similar prod refinement, while others held that it was ucts. theoretically unsound. As a matter of fact, Goldwater, in 1936, Since the publication of Levine and found some correlation between the specific Fatty's paper we have routinely used the gravity of urine and its silica content.2 specific gravity adjustment in calculating 2. The specific gravity must he accurately urinalysis results. Our laboratory analyzes, measured and expressed in relation to that on the average, between 1,000 and 2,000 of water at the same temperature as the urine samples a year for heavy metals and urine sample. If the specific gravity of the ( solvent metabolites. In addition, during the urine is related to that of water at 4 C, as is past ten years we have been carrying out a frequently done, the adjustment will result in too high a value, particularly with dilute Table 2.--Excretion and Body Size samples as shown in Table 1. If a urinometer calibrated against water A, Sq m Litersg per 24 hr (av) MF at 4 C is used, a suitable correction should be made before employing the specific gravi ty adjustment. 1.44 ' 1.56 0.68 0.6S 3. In the vast majority of cases, adjusted 0.69 values are more consistent than actual con 1.65 0.79 0.63 centration values. This is particularly true 1.75 1.84 1.94 0.91 0.89 0.98 . 0.65 0.71 0.85 when some of the samples are dilute. This superiority is evidenced by consistently 2.01 0.99 ... lower average deviations from the mean, 2.13 2.26 1.05 1.17 ... ... among groups of samples from workers with similar exposures, or consecutive samples Arch Environ Health--Vol 18, June 1969 : 1 ' I? i $ l. ' F1r- wr rs> J DUP050312883 998 SPECIFIC GRAVITY IN URINALYSIS--ELKINS & PAGNOTTO Table. 3--Adjusted Daily Urine Volume and Diet Subject D M litersg pet 24 hr BSA, Sq m Low-Protein High-Protein 1-67 1.92 0.47 0.69 0.98 1.07 Table 4.--Diet and Specific Gravity-Actjusted Concentration Contaminant Excreted (Hypothetical) Subject D Diet mg/24 hr mg/liters: /Low-protein 0.20 0.43 \High-protein0.200.20 from the same individuals, when adjusted rather than unadjusted values are used. 4. In comparison with 24-hour or shorter timed samples, the specific gravity adjust ment has the great practical advantage of eliminating dependence on the intelligence and reliability of the subject. One or both of these qualities are lacking in many workers; even under the most favorable circum stances, short of confinement to a hospital bed, we have found it very difficult to obtain reliable timed samples from workers, includ ing supervisors and skilled technicians. 5. There are a number of factors which will affect the rate of excretion of various solid components of urine, and, thereby, the specific gravity-adjusted volume of urine voided in a given time. We have enough data and information to warrant further dis cussion of four of these factors, particularly as they affect the interpretation of urinalysis results. (a) Body Size.--It would appear axio matic that, other things being equal, size would show a positive correlation with rate of excretion; that is, a large man will, on the average, excrete more urine (adjusted or unadjusted) per day than a small man. For many purposes body surface area (BSA) is considered preferable to weight as an index of body size. Body surface area can be cal culated approximately by means of a formu la involving both height and weight, and we have used this method of estimating size. According to our data, the rate of excre tion of total solids, as evidenced by the daily voidance of urine--adjusted to specific grav ity 1.024--does show a statistical relation ship to BSA. Table 2 lists the average val ues for male and female workers, classified in some nine different size groups. Hie ex cretion rates are, for the most part, projected from timed samples of six to ten hours' duration, but include a number of actual 24-hour samples. No marked differences were found between the two types of sam ples, but the "actual" values were, on the average, slightly lower than the "projected" values.3 It is seen that the average rate of excre tion of the largest size group (average weight, 103.4 kg [229 lb]) is not quite twice that of the smallest (63.5 kg [119 lb]). If we accept the logical premise that rate of breathing and harmful dose are also relat ed to BSA, it would follow that the rate of excretion of a toxic substance must be cor rected for body size before it can be an accurate index of the hazard. Table S.--Comparison of Dilute and Concentrated Sweating Sample Results Dilute Concentrated Lead Found Lead Found Crea tinine, Creatinine, Subject: Sp G gro/liter mg/liter mg/24 hr mg/IJtersg Sp G gm/liter mg/llter mg/24 hr mg/litersg L* 1.022 1.60 0.20 0.24 0.22 1.026 3.05 0.24 0.15 0.22 W* 1,018 1.60 0.29 0.45 0.39 1.028 2.40 0.38 0.34 0.32 R* 1.024 2.02 0.22 0.27 0-22 1.029 2.65 0.19 0.13 0.15 Bt 1.022 1.84 0.40 0.35 Av 1.022 1.76 0.28 ' 0,33 * Exercised in laboratory, t Subjected to hot work at secondary smelter. 0.45 0.32 1.037 1.030 5.48 3.40 0-87 0.42 0.29 0.23 0.61 0.32 Arch Environ Health--Vol 18, June 1989 f SPEC ( Table 6 Sample* i Normal i I Normal Normal Normal i Sugar present * From five coworkt i i Hence, as betw i i t a toxic substance justed concentrat i vantage that it is (b) Diet.--It the quantity of u related to the p; The excretion of be increased by s cal data from tl Table 3.4 If diet does n absorption) of hi i t i olites, etc, and if rected for body i absorption, the .< iii will lead .to err specimens from ; i particularly with Assuming a cons: metal for subject i gravity-adjusted edly when on the Table 4.'1 A samj diet would indie: sure as that obi protein. ! (c) Exercise < 4 salt, and other s< mally accompani volume, and also ! total solids. Duri mg the specific voided per hour i found under nor tion arises as to tions of heavy n and solvent metal We have carri ration experimei t workers. In som were not obtaim-c which did seem t in Table 5. I it DUP050312884 u& SPECIFIC GRAVITY IN URINALYSIS--ELKINS & PAGNOTTO 999 Table 6.--Effect of Sugar Lead Found Using Adjustment for Sample* SG Normal Normal Normal Normal Sugar present 0.25 0.20 0.21 0.16 0.04 * From five coworkers. Creatinine 0.20 0.24 0.22 0.16 0.17 Hence, as between the rate of excretion of a toxic substance and the specific gravity-ad justed concentration, the latter has the ad vantage that it is little affected by size. (b) Diet.--It has long been known that the quantity of urea excreted in the urine is related to the protein content of the diet. The excretion of other solids also appears to be increased by a high-protein intake. Typi cal data from the literature are shown in Table 3.* If diet does not affect the excretion (or absorption) of heavy metals, solvent metab olites, etc, and if the rate of excretion (cor rected for body size) is a true index of absorption, the specific gravity adjustment will lead to error when applied to urine specimens from persons with varying diets, particularly with respect to protein content. Assuming a constant excretion rate of heavy metal for subject D of Table 3, the specific gravity-adjusted values would differ mark edly when on the different diets, as shown in Table 4.-* A sample taken on the low-protein diet would indicate twice as severe an expo sure as that obtained on the diet rich in protein. (c) Exercise and Sweat.--Loss of fluid, salt, and other solids in perspiration is nor mally accompanied by a reduction in urine volume, and also in the rate of excretion of total solids. During a period of heavy sweat ing the specific gravity-adjusted volume voided per hour may be as little as half thatfound under normal conditions. The ques tion arises as to whether or not the excre tions of heavy metals, radioactive isotopes, and solvent metabolites are similarly affected. We have carried out a number of perspi ration experiments on lead and mercury workers. In some cases meaningful results were not obtained. (Hie findings in four cases which did seem significant are summarized in Table 5. In three of lire four cases, concentration of the urine sample is accompanied by an in crease in the actual concentration of lead. This confirms the premise on which the specific gravity adjustment is based. In every case, moreover, the excretion of lead per 24 hours is greater in. the dilute than in the concentrated samples. This finding would be consistent with reabsorp tion of lead in the kidney tubules, and ex cretion of significant amounts in the sweat. Loss of body fluid as sweat may exceed the amount excreted in urine over a period of several hours, by a factor of five to ten. The composition of sweat approximates that of blood plasma for many ingredients. On the other hand, due to the fact that the volume of plasma filtered by the kidney in the course of a day is more than 100 times the volume of urine excreted, the concentra tion in the urine of those ingredients which are not reabsorbed in the kidney tubules, may exceed the plasma concentration by an equivalent amount. In the case of such sub stances, the loss through the sweat would be relatively unimportant. On the other hand, the loss in perspiration of a substance such as salt, which is strongly reabsorbed in the kidney, may be as great or greater than the excretion in the urine. (d) Samples Containing Sugar.--Occa sionally urine specimens of high specific gravity have been found to contain large amounts of glucose. For such urines, the specific gravity is not a good index of "con centration." Determination of the osmolality or creatinine value usually reveals that the sample is dilute with respect to ingredients other than sugar. In such cases expression of results as "milligrams per lItersK," or even "milligrams per liter" may lead to erroneous conclusions. In Table 6 the lead contents of urine from a number of grinders in a bronze foundry are listed. One of the men consistently ex creted sugar, and the urine, while of high specific gravity, had a low creatinine con centration. When the lead contents of the samples were calculated, using the specific gravity adjustment, this man alone was found to have no significant exposure. How ever, if the results of the analyses are ex pressed using a creatinine adjustment (1 mg of lead per 2 gm of creatinine), the exposure Arch Environ Health--Vol 18, June 1969 Y K. - \, P- .b: \ t h[ i h f- s; fruujjfufivf DUP050312885 i^wt..tf.'i..ijii..f>,i;f).' ii-!M..',r;Wi,,i;ii 1000 SPECIFIC GRAVITY IN URINALYSIS--ELKINS & PAGNOTTO of this individual is found comparable to His creatinine output, during the same peri that of has coworkers. od, was at a rate of 1.75 gm/day, compared Data from samples known to contain sug with an average of 1.92 gm for workers with ar have been excluded from our statistical BSAs between 2.10 and 2.19 sq m. compilations (Table 2). The lowest credible excretion was 0.34 Maximum and Minimum Credible Excretions liters,, per day, obtained from a 41-year-old chemist, who submitted a 24-hour sample. His creatinine excretion was 1.0 gm/day; It has been shown that three nonpatholog- the average for his size group (1.60 to 1.69 ic factors--body size, diet, and sweating, sq m) is 1.38 gm. each may affect the rate of excretion of It is seen that the excretion of A, in terms specific gravity-adjusted urine by a factor of of adjusted volume per 24 hours, exceeds approximately two. The maximum variation that of Q by a factor of seven. This is in rate f excretion, due to these factors surprisingly close to our theoretical value of alone, would be a ratio of approximately eight, the maximum probable difference re eight fo one. That is to say, a small man sulting only from variations in size, diet, (53.5 kg [120 lg]) on a low-protein diet, and degree of perspiration among male who is sweating profusely, could be expected workers. Subject A is much larger than Q, to excrete total solids at approximately one but we have no knowledge of the diets of eighth 1% X }A X VS = Vsl the rate of a these men. It appears unlikely, however, large man (104.1 kg [230 lb]) who is on that Q, a scientist, was sweating heavily } a high-protein diet and is not perspiring. throughout the 24-hour period. Hence it is ';'i We have examined the individual values probable that factors other than those which among approximately 600 timed samples, we have considered are partly responsible 1 collected, from some 400 workers, and select for the marked differences in rate of excre ed the two with the highest and lowest tion. A "credible" excretions, respectively, in terms If the lead values are considered, each '"'l of litecSg per day. The pertinent data are man would be considered mildly exposed on shown in Table T. Since adequate supervi the basis of his specific gravity-adjusted val sion of sample collection was not provided in ue. If, on the other hand, the 24-hour excre every case, we have rejected those samples tions are considered, A would be well in the which did not meet an arbitrary criterion of harmful exposure range, while Q would ap i reliability, namely, a creatinine excretion pear to have no significant exposure. Correc within 25% of the average for the same size tion for body size does not alter the situation group as the worker. materially. A number of the timed samples collected In Table 8 comparable data are given for indicated 24-hour excretions below 0.34 two mercury workers. These men are of litere bid were rejected because of low crea comparable size, but the 24-hour excretion $ "M tinine values. The lowest value was 0.18 of total solids (litersg) was nearly four literg, with a projected creatinine excretion times greater for K than for W. As a result, of 0.30 gm/day. A smaller number of results the specific gravity-adjusted mercury value on the high side were also rejected. The for W is greater than that of K by a factor highest value was 3.52 liters,, per day, with of over four, in spite of the fact that the a daily creatinine excretion of 6.5 gm. rates of mercuiy excretion (1 mg/24 hr) In assembling the data for Table 2, values are approximately the same. If we consid were generally rejected if the rate of creati ered only the specific gravity-adjusted val nine excretion differed by more than 50% ues, we would conclude that W is harmfully from the average for the same size group. In exposed, but that the exposure of K is with selecting "credible" excretions, however, the in safe limits. On the other hand, if wc stricter criterion of not over 25% deviation considered only the 24-liour excretions of from the mean was chosen. mercury, our conclusion would be a border The highest credible excretion was 2.39 line exposure (0.25mg/day) for each man. liters,, per day, projected from a 514-hour The data at hand do not enable us to sample from a 35-year-old foundry worker. decide which of the preceding interpreta- Arch Environ Health--Vol 18, June 1969 "ST DU P0 50312886  SPECIFIC GRAVITY IN URINALYSIS---ELKINS & PAGNOTTO 1001 Table 7.--Maximum and Minimum Credible Excretions Subject Height Weight, ib BSA. Sq m UtersE per 24 hr Creatinine per 24 hr (gm) Lead mg/literg mg/24 hr A 6 ft tin 209 2.19 2.39 1.75 0.13 0.31 O 5 ft 4 in 138 1.67 0.34 1.10 0.10 0.03 Table 8.--Excretions of Two Mercury Workers Subject KW Height Weight, Ib BSA, Sq m Litersg per 24 hr Creatinine per 24 hr (gm) Mercury mg/literg mg/24 hr 5 ft 10 in 175 1.97 2.13 2.12 0.11 0.23 5 ft 10 in 147 1.83 0.54 1.52 0.43 0.26 tions is the more valid, in either of these situations. Of the factors which we have considered, body size and sweating probably affect rate of excretion more than they in fluence concentration adjusted for specific gravity. Oh the other hand, normal varia tions in diet do not influence the rate of excretion of toxic substances, so far as is known, but they may affect the total solid content of the urine and thereby the specific gravity-adjusted values for many individual substances. Formation and excretion of urine is a complicated process, and many unknown variables contribute to the total rate of ex cretion, as well as to the rates of excretion of many individual substances. In cases such as those given in Tables 7 and 8, a logical procedure would be to average the results obtained by the two methods of calculation. The resulting value can be considered an exposure index for the hazard in question. In the above cases the lead exposure indices of A and Q would be 0.22 and 0.07, respec tively; the mercury exposure indices of W and K would be 0.37 and 0.17. This investigation was supported by Public Health Service research grant 5R.01-UI-00402. References 1. Levine, L., and Fahy, J.P.: Evaluation of Uri nary Lead Determination, I Industr Hyg Tox 27:217223 (Oct) 1945. 2. Goldwater, LJ.: The Urinary Excretion of Silica in Non-silicotic Humans, -I Industr Hyg Tox 18:163- 166 (March) 1936. 3. Elkins, Il.B., and Pagnolto, L.D.: Is the 24- Hour Urine Sample a Fallacy?, Amer Industr Hyg Assoc J 26:456-460 (Sept-Oct) 1965. 4. Price, J.W.; Miller, M.; and Hyman, J.M., Jr.: Relation of Specific Gravity to Composition and Total Solids in Normal Human Urine, J Clin Invest 19:537554 (May) 1940. 5. ' Kuno, Y.: Human Perspiration, Springfield, XU: Charles C Thomas, Publisher, 1956, pp 251-276. 6. Pitts, R.F.: Pkysiohgy of the Kidney and Body Fluids, Chicago: Year Book Medical Publishers, Inc., 1963. , i* [; ' C. r i- s' S'- \ . iy- ir r. PHOTOSYNTHESIS The general kinds of pollution that may enter a stream due to man's activities are suspended solids, toxic pollutants, organic pollutants, and heat. The most obvious effect of a suspended solids load is to reduce light penetration into the water. Light is important for the process of photosynthesis which produces oxygen and thus replaces the oxygen used by respiration. It has been shown that photosynthesis is usually move important than turbulence in generating oxygen for the aquatic ecosystem. However, this may vary depending upon circumstances. Our studies have shown that most organisms live in the photosynthetic zone. . Therefore, if this photosynthetic zone is reduced, the area for species occupancy is also reduced for most animals.--Patrick, R.: Aquatic Communities and the Problems of Water Quality, General Systems 13:125-127,1968. Arch Environ Health--Vol. 18, June 1089 - wrwr? l: r. i ; j ip DUP050312887