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C\q&^ -^g o Is the 24-Hour Urine Sample a Fallacy? HERVEY B. ELKINS, PLD., and LEONARD D. PAGNOTTO Division of Occupational Hygiene, Massachusetts Department of Labor and Industries, 286 Congress Street, Boston, Massachusetts ` @ A study has been made of the use of 24-hour excretion (actual or projected) in comparison with the concentrations adjusted for specific gravity, as measures of exposure to lead, mercury, benzene, and trichloroethylene. It has been found that timed samples show a somewhat greater variation than values adjusted for specific gravity. When different individuals are considered, differences in body size affect the rate of excretion, as indicated by timed samples, to a certain extent. Other factors, however, appear to be of greater importance. The evidence presented, although not conclusive, suggests that the value adjusted for specific gravity is a better index of exposure than is the timed sample. i Introduction tration of heavy metal, solvent metabolite, or radioisotope in the urine will also vary rTHE LITERATURE of industrial medi- greatly. In such cases the rate of excretion is cine and industrial hygiene pays slight much more nearly constant than the concen attention to methods of expressing urinalysis tration. ' `* results. A few discussions of this problem, Ingestion of a pint of beverage may in- ' most of them limited to the element lead, crease the flow of urine more than eightfold have been published1-8 but are largely ig for a two-hour period. Our laboratory has nored by workers with other metals, radio received 24-hour urine samples that varied active substances, solvents, and insecticides. in volume from less than 350 ml to more than Papers on these materials usually report find- 3500 ml. Some authorities discount the im ings on the basis of 24-hour samples, or, not portance of compensating for such variations, infrequently, timed samples of shorter dura on the ground that they are so rare as to be tion. When even short timed samples can- unimportant. It has been our experience, i ' not be obtained, the results are ordinarly however, that about 10% of the urine sam j given as parts per million, microcuries per ples received are so dilute as to create a | liter, or other unit of concentration in the serious error if adjustment is not made. Dur I urine, invariably accompanied by an apology ing a 12-inonth period, for example, mote ; | for not using timed samples, than 118 urine specimens with a specific : j If we are dealing with averages, either pro- gravity of 1.012 or less were submitted t*,a* i cedure may lead to approximately equivalent our laboratory, for analysis for lead, mercury, j results. In individual cases, however, especi- phenol, trichloroacetic acid (TCA), or ar j ally when, owing to variation in fluid intake, senic. j the rate of mine excretion varies, the concen- Adjusting for Specific Gravity This paper was presented at the Annual Meeting of the American Industrial Hygiene Association, Philadelphia, Penn sylvania, ApiH 2G, 19u4. This work was supported by Public Health Service Re search Grant 00055-06, from the Division of Occupational Health. Twenty years ago Levine and Fatty pro posed that variations in lead urine values be compensated by adjusting the concentratieu according to the specific gravity of the urine. - N36927 DUP050312888 i.-im'flH Industrial Hygiene Association Journal Ta b l e I . Excretion of Several Industrial Poisons in Successive Samples of Urine Substance Lead Mercury Uranium Lead Trichloroacetic acid Weighted average Duration 24 hr 24 16 4 4 "Adjusted for specific gravity. Number of Subjects 19 41 ' 632 Average Percentage Deviation 24-hr Sample Adjusted Cone.* <mg/24*hr) (mg/Iitcr) % 14 3250 8 9% 15 33 185 18 14 .457 li.i'v suggested the formula: mg/liter (at Sp.Gr. 1.024) = (mg/liter) X 0,024 specific gravity--1.000 ........ - plete. The results calculated on the basis of the specific gravity adjustment-were more consistent than those baspd on the 24-hour excretion (projected or actual): .dwrc the. left half of the equation is the . .line adjusted to a specific gravity of 1.024, . :.d the actual specific gravity of the urine Ta b l e II '; Variation in Excretion of Several Industrial Poisons within Groups Having Similar Exposures. i-nple is used on the right side of the equa- Average Percentage Deviation During a study of various facets of excre Ti of industrial poisons in urine, we have ..'do a number of comparisons between duos obtained by this procedure and those aired by use of timed samples. The cus' 'inary procedure in problems of this sort is Substance Number of Groups Lead Trichloroethylene Dichlorobenzcne . 18 13 4 2 Weighted Average. 24 hr Sample Adjusted Cone.* (mg/24-hr) (mg/liter) 25% 30 32 25 27 2119% 16 24 39 aAdjustedfor specific gravity. 1 collect successive urine samples from an dividual and determine the extent to which d:o two values in question vary. We have '' "lie this with workers exposed to four dif- One. possible reason for this difference, which we considered, was body size. It seems logical to assume that a large man will in * rent hazards, with the results shown in Table I. The average deviation was, in general, less '"r long than for short samples. In the latter i! the deviation was significantly less when hale more dust or fume, and absorb and excrete more of the substance or metabolite, than a small man in the same environment. Our data on timed samples from lead work ers have been split into two groups, consist d:o specific gravity adjustment was used than lion timed excretions were considered, i hose deviations are notably lower than those ing of individuals above and below average size. The results are given in Table III. As a measure of size we have used body surface 'uained by Levine and Fahy2 and, in the area, as calculated from the tables prepared of the timed samples, by Barnes.1 according to the formula proposed by Du - further comparisons were made by obtain- urine samples from different members of ;oups of'workers, all with similar exposures. * Dio results are summarized in Table II. In Ta b l e III Relationship between Body Size and Lead Excretion in Urine '!'t* majority of cases, timed samples of six right hours, projected to 24 hours, were ':'cd. It was found that such samples were, " the main, more reliable than 24-hour samsince, on questioning of the workers, the Item Number of subjects Average body area, in2 Lead excretion, mg/24-hr Lead excretion, mg/Iitcr Body Size Croup Smalt Large 39 1.80 0.154 0.174 35 2.05 0.193 0.180 :ior were frequently found to be incom "Adjusted for specific gravity.  458 September-Oclobcr, bois.1 The average exposures of the two groups are similar, if measured by the specific gravity adjustment, but the. excretion per day is significantly higher for the larger men. A different but consistent finding, is ob tained if our data on a group of men exposed to benzene are similarly treated (Table IV). Ta b t ,r IV Relationship between Body Size and Phenol Excretion of Subjects after Exposure to Benzene Item Number of Subjects Average body area, m* Phenol excretion, mcr/24-hr Phenol excretion8, mg/liter Body Size Group Small Barge 6 1.72 170. 224. 4 1.95 176. 179. aAdjustcd for specific gravity. In this case the values adjusted for specific gravity indicate that the smaller men are on the average more heavily exposed than the large men. The rate of excretion per 24 hours, however, is slightly greater for the larger men. If these findings are typical, it must follow that the total excretion of large men, based on volume adjusted for specific gravity, will on the average exceed that of smaller men. Our data on the average 24-hour urine ex cretion of various size groups are given in Table V. VTa b l e Relationship between 24-Hour Volume of Urine Excreted and the Body Size of Subjects Surface Area of Body, ms 1.25 - 1.69 1.70 - 1.79 1.80 ~ 1.89 1.911 - 1:99 2.00 - 2.09 2.10 - 2.25 Urine Volume, litcrs/24-hr.a Projected Actual 0.82 0.98 0.96 1.01 1.03. 1.17 0.62 0.86 0.84 0.87 0.80 1.10 Adjusted for specific gravity. There is a marked difference in exciei-;, between the smallest and largest sizes: s; differences are less noteworthy in the in-,, mediate groups. The projected values consistently higher than die actual vale owing probably to diurnal variation in r.c of excretion--the samples that were pmji-... ed'were nearly all taken during the day, when excretion is generally at a hi"!., rate than during the night.5 We also obtained samples from pairs <: workers who worked side by side or h.v: similar jobs in the same work area. Com parisons of urine excretion of different ha;, ards from two such pairs are shown in Tab;VI. As we might predict, the larger men shuv. a significantly greater daily excretion, where as the differences in the values adjusted fm specific gravity are much less. In the ca-i of foundry workers A and I, however, tl.. differences in daily excretion are much greater than would be expected from the size (lit ferenccs, since, although A is a very lany man, his coworker, I, is also well above avci age size. A similar picture can be obtained from paired workers of equal size, one of whom show's a high rate of excretion, and the edict a low one. For instance, two molders ant! two pourers in the same foundry where A ami I worked showed similar variation, although all were of' about equal size, as shown in Table VII. These differences bring out the fact that the 24-hour excretion, in terms of volume, adjusted for specific gravity varies gn-uth among individuals, regardless of difference', in size, and only when averages are consid ered does size appear to be a significant fac tor. There are undoubtedly several reasons for Ta b l e VI Excretion of Paired Workers Worker A l P F Body Area (in2) 2.19 2.04 1.94 1.57 Hazard 24-hr Sample (mg/24-hr) Lead Lead Benzene (phenoH Benzene (phenol) 0.22 0.09 252. 143. Adjusted lor specific gravity. Adjusted Cone.6 (mg/litcrl 0.11 0.14 152. 119. DUP050312890 .iuicriean Industrial Hygiene Association Journal Ta b l e VII Urinary Lead Excretion of Paired Workers of Equal Body Size ' Worker D S Ab T Bod(yVA)rea 1.75 1.78 1.83 1.89 Job Moldcr Molder Pourer Pourer 24-hr Sample (mg/24-hr) 0.125 0.21 0.29 0.145 Adjusted Conc.a (mg/liter) 0.165 0.12 0.22 0.23 "Adjusted for specific gravity. Ta b l e VIII Average Urinary Lead Excretions of Foundry Groups Number in Group 6. 9 Jobs . Average Body Area <m"> Melters and nourers Molders 1.93 1.88 "Adjusted for specific gravity. Lead in Urine mg/24-hr mg/litcr* 0.172 0.182 0.202 0.127 Lead in Air tmg/ccp) 0.32 0.19 459 tliis, such as diet and kidney function. It seems unlikely that there is a close re lationship between the volume Of air breathed nr the' amount of fume or vapor absorbed, and the rate of excretion of urine. Our studies of these men, A and I, and S and D, included four investigations over a 14-month period. The findings were es sentially the same in each case. If we pos tulate that these men, who had all worked fur years in the foundry industry, have reached essential equilibrium so far as lead intake is concerned, this means that they are 'xrrcting about as much as is being absorbed. Since A and S are excreting nearly twice as much lead in thfe urine as are I and D, it must follow that they are eliminating less via "ilior channels, if total absorption and ex cretion are the same. This means that the hotly burden of lead in A and S is no great er. and in fact is probably less, than that of I and D. That this may be so is suggested by die higher values adjusted for specific gravity f the latter men. If we accept the above reasoning, the nec- 'Uiry conclusion is that milligrams of lead pi i liter, adjusted for specific gravity, is a bet'<r index of lead absorption than is millicr.uus pgr 24 hours. Further evidence fav1,1 able to this theory may be found in Table ^ HI. Based on 24-hour excretion, the ex,rf,i|>re of the molders is slightly greater than that of the melter-pourer group. The values, adjusted for specific gravity, however, indi cate a considerably higher lead absorption by the latter. In addition, the measurements of lead in air confirm the greater exposure of these men in comparison with the molders, who do not themselves handle molten metal. In October 1963, blood samples were ob tained from the melters and pourers and from others, including floor and platform workers and molders. Unfortunately, the foundry had been working only a few days a week during the summer, and lead levels were well re duced over those found during the winter and spring. The findings are summarized in Table IX. The group averages confirm the greater exposure of the melters and pourers in com parison with the others studied. In the indi vidual cases, workers A and S have higher blood leads than coworkers I and D, even though for the latter the values adjusted for specific gravity are higher. Pourer T, how ever, has a higher blood lead than Ab. But the differences in all cases are too slight to be conclusive. One possible reason for the differences noted between the melter-pourer group and the molders lies in the higher temperatures to which the pourers are subjected. It is probable that loss of perspiration may be a major factor in causing the lower total excre- -7 : DUP050312891 460 September-Oclobei, Ta b l e IX Urine and Blood Lead Values of Foundry Workers Number or Identification Job . Lead in Urine mg/24-hr' mg/liter8 Lead in Blood mg/100 gtn blood -. 6 Mcftcrs-pourcrs 0.153 0.171 0.059 /, 7- ' Motdcr&-platform workers 0.091 0.095 0.044 A Platform worker 0.11 0.C7 0.058 I Platform worker 0.07 S Moldor 0.15 0.12 0.09 0.047 0.Q54 D Molder 0.10 0.11 0.046 Ab Pourcr 0.23 0.IS 0.055 T Pourer 0.20 0.23 0.066 ^Adjusted for specific gravity. lion by these men in comparison with the but he does not suggest another procedun molders, whose .exposure to heat, as well as that will work for samples of all ranges u! to fume, is somewhat less. . dilution. Conclusion As between the timed sample and the spe cific gravity adjustment, however, we believe Although these data, in general, fall into that the data we have favor the latter a- 11; j the pattern indicated above, more study is providing the more meaningful results ' M needed, in particular, more blood lead deter minations on men with higher exposures, be References fore we are warranted in concluding defi nitely that the value adjusted for specific gravity is more significant than the timed 1. Ba r n e s , E. C.t Possibilities of Control of Lead Exposure- by Examining Less Than 24-Hour Urine Samples. I Ind. Hyg. Toxicol. 21: 464 (November 1939). sampler It seems likely that, if this conclu 2. Le v in e, L., and J. P. Fa h y : Evaluation of Uritt.u- Lead Determinations. 1. The Significance of the Siu-cilic .f sion is confirmed for lead, it will also apply Gravity. J. Ind. Hyg. Toxicol. 27: 217 (October 1915;. to other elements and metabolites of organic compounds, although not necessarily to all such substances. We do not intend to imply that the specific 3. Br u u s o a ar d , A.: Vurderingen av Blyverdicr i Urin. Nord. Hyg. fidskr. 42: 71 (1961). 4. DuBoia, E. F.: Basal Metabolism in Health and Dij.-w (Lea, Philadelphia, Pennsylvania, 1927). Cited in Tf>t, Physiological Basis of Medical Practice (C. H. Best ;m.l N. BL Taylor, Eds.), 3rd Ed., p. 898. The Williams A Wilkins Co., Baltimore, Maryland (1943). gravity adjustment is necessarily the best method of expressing urinalysis results. Kehoe has criticized both this method and. the 24hour sample .as being physiologically unsound. 5. Bes t , W. R.: Physiologic Factors m Urinary Crcafuun* Excretion, Report 118, Medical Nutrition Laborator*. U. S. Army, Fitzsintons Army Hospital, Denver, 0*1*** nado' (October 22, 1933). 6. Ke h o e. Ro ber t A.: Industrial Lead Poisoning. Tn in dustrial Hygiene and Toxicology, 2nd rev. ed., Yol. I* p. 957, Interscience Publishers, New York (1963). , Facts About Lead The Lead Industries Association has prepared a booklet. Facts About Lead and Industrial Hygiene, which will be of interest to many persons in the areas of occupational health and industrial hygiene. A historical narrative of the facts ' and fallacies regarding lead poisoning is presented. This is followed by sections on the balance of lead in the body and the control of industrial exposures to lead in various forms. A section on safeguards and practical suggestions is also included. Copies of this publication may be obtained from the Lead Industries Association, Inc., 292 Madison Avenue, New York, New York 10017. .i M DUP050312892