Document reBa2DYNOvXzrXL79mzVGXb9G

TRANSLATION: Pietrova, A. and D. Bakalov: INVESTIGATION OF URINE FOR PORPHYRIN IN SOME OCCUPATIONAL POISONINGS. (Izsledvane na urlna za porfirini pri nyakoi profesionalni otravyaniya.) Khigiena (Sofia), Vol. 6, No. 4, pp. 37-41, 1963. The literature contains little on the use of the coproporphyrin level in the urine as an indicator during early diagnosis in various occupational dis eases [3, 6 and 7]. Insofar as such information exists, it relates mainly to coproporphyrin of type III. Such data are known for some cases of lead poison ing. For example, M. I. Gusev [4] reports on the effect of small concentrations of lead on porphyrin metabolism in children. Along with that it should be noted that the data on the coproporphyria level in most of the cases are given on the basis of qualitative or semi-qualitative investigations (spectroscopic, for example). In connection with the unsatisfactory state of the question of early diag nosis in occupational poisoning, we posed ourselves the task of verifying: Cl) the extent to which coproporphyrinuria is a certain, early and sensitive indicator in the above-mentioned cases and (2) the extent to which it is mani fested in intoxications on which information is lacking in the literature* For that purpose, coproporphyrin was determined in the urine of persons poisoned or under the influence of various poisons -- nitrobenzene, lipoid solvent, heavy metals, etc* The coproporphyrin level was determined with the Fischer- / Say method as modified by D. Bakalov [1]. In some of the cases the levels were investigated qualitatively and for urobilin. In parallel with the above investigations, hepatic tests were conducted on the patients and the questionably ill. The urine was taken from patients in the Clinic of Occupational Diseases N40760 and Poisonings of the Chair of Hygiene and Labor Hygiene of the Higher Medical Institute in Sofia, the Clinic of Occupational Diseases and Poisonings of the NIOTPZ (the Scientific Research Institute of Poisonings and Occupational Dis eases) and from clinically healthy persons working at the D* Dimitrov State Rubber Plant* The results obtained were compared with those from the hepatic tests [Weltmann, MacLagan, cadmium test and Gross, and in certain cases also TakataAra], and also with the results of investigations of urobilinogen and urobilin in the urine (Table 1)* * TABLE 1. TOTAL NUMBER OR URINE INVESTIGATIONS 59 Number of urine specimens with coproporphyrin up to 100 y/24 hours 29 Number of urine specimens with coproporphyrin above 100 y/24 hours 30 with positive hepa tic test in the blood 10 with increased quantity of uro bilinogen or uro bilin in the urine 12 with negative hepa tic test in the blood 20 with unincreased quantity of uro^ bilinogen or uro bilin in the urine. is It Is evident from Table 1 of 59 urine specimens of persons poisoned with various poisons which were investigated for the quantity of coproporphyrin, 30 give porphyrin (coproporphyrin above 100 y in the urine taken in 24 hours)< 2 i DUP050058715 That norm was determined by us in the urine of a large number of healthy per sons by the same method as used in the investigation. It also coincided with norms given in the most recent literature [3, 5]. Of the 30 cases (Table 1) established by us to have porphyrinuria, in 10 positive results were obtained from investigations of hepatic tests in the blood, and in 12, positive results for urobilinogen and urobilin in the urine. Statistically processed, the above data show that the percentage of investi gated persons with coproporphyrinuria (above 100 y) was between 31.5 and 70.5%, whereas the interval of positive hepatic test among them varies from 7.5 to 59.1%, and that of positive results of urobilinogen and urobilin in the urine, between 13% and 67%. That statistical verification proves the complete reliability of the data. It is clear that the increased production of coproporphyrin in the urine is a very early and sensitive indicator of liver damage* surpassing all the rest. It also must he noted that in a majority of our cases it is a matter of a slight degree of poisoning or rather of toxic imitation which clinically was so poorly expressed that often the original diagnosis of "doubt of poisoning" was replaced by "neurosis" and "neurasthenia". Consequently, the qualitative investigation for coproporphyrin is of essential importance for the early diag nosis of occupational poisoning and especially of occupational effects. The urine specimens investigated by us derived from persons with the following poisonings or toxic effects (Table 2). p?* 3 DUP050058716 TABLE 2, .Type of poisoning or effects Benzine Benzene Diraethylsulfate Lead Carbon monoxide Mercury Uranium Copper Sulfurous gas TNT Methyl chloride Nylon Aniline Acetone Potassium cyanide Zinc + lead + copper NaOH 4- liquid soap Nicotine HjS + Beriev (Beriliev - beryllium) dichloride Investigation of urine for quantity of coproporphyrin cases 29 no. of those cases with coproporphryin a 1i 10 44 22 21 10 11 11 43 11 10 22 3i 31 I0 11 10 10 4 DUP050058717 It is clear from Table 2 that 19 types of poisonings were investigated, three of which were combinations. Coprop orphyrin was established in 13 types of intoxication. Those were poisonings with benzine, benzene, lead, carbon . monoxide, mercury, copper, sulfurous gases (SO^ and SO^), TNT, methyl chloride, aniline, acetone, potassium cyanide and sodium hydroxide + liquid soap, Of the enumerated poisonings, only for acetone, benzene, lead, aniline, and carbon monoxide are there literature data indicating that they cause por- hyrinuria, and that was only qualitatitively established. Quantitative inves tigations conducted by us show that that can also occur in intoxications with TNT, benzine, copper, sulfurous gases, mercury, methyl chloride, potassium cyanide, and sodium hydroxide + liquid soap, in which damage is done to the parenchyma of the liver, the spleen, bone marrow, the reticulo-endothelial system, nervous system, etc. Hence it was established, although with caution because of the small number of cases, that the group of poisonings in which there is disturbance of porphyrin metabolism is broader than was known up to now. As a very large percentage of the urine specimens investigated by us (29) were from persons poisoned or subjected to the effect of benzine, that made it possible to make a deeper study of coproporphyrinuria in that type of poison ing and obtain more reliable results. The number of cases with benzine poisoning coming from the mentioned clinics was supplemented by workers from the G. Dimitrov State Rubber Plant who had been exposed to the effect of large concentrations of benzine. To evaluate working conditions at the plant (concentration of benzine vapor, dustiness and microclimate), generalized results of an investigation 9\ made on October 11, 1962 by the chemical laboratory under the Second SES were used (Table 3). _ ] i i f \ j * j * 4 DUP050058718 TABLE 3 3 mg/m Mean d u st concen- Mean benzine concen tra tio n , m g/liter tra tio n , Number o f te s ts Shop Relative humidity Air velocity Remarks Rubberizing 3 1.36 -- Mixing 3 0.56 60.2 Confection 4 1.57 -- Vuleanizer Average 3 0.77 1.06 60.2 Above maximum allowable Above maximum allowable Above maximum allowable Above maximum allowable Above maximum allowable Above maximum allowable Above maximum allowable Above maximum allowable Aspiration of the air Ventilation of the work Ventilation of the work The data of Table 3 show that the workers in the G. Dimitrov State Rubber Plant are in contact with high concentrations of benzine vapor (mean for the entire plant, 1.06 mg/liter)which exceeds the sanitary norm for benzine (0.3 mg/liter -- News, No. 66, August 8, 1952). As the benzine concentration is highest in the confection shop, tests were made of urine specimens of 18 workers (men and women) from it. The urine samples were taken during the working time of eight hours, when the measured results were recalculated for 24 hours (Table 4). 6 DUP050058719 TABLE 4. TOTAL NUMBER OF INVESTIGATED URINE SPECIMENS. 29 Of patients 11 With porphyrinuria (above 100 y ) Of workers (G. Dimitrov State Rubber Plant) 18 With porphyrinuria (above 100 y) initials Iv. Khr. A, V. G. F, V. I. L. A. lv. Ch. G. D. S. T. St. M. N. A. D. copropor phyrin, Y% 11 40 20 18 18 22 24 copropor phyrin, y/24 116 600 240 300 260 220 360 initials T, K. K. 2. Tsv, P. M. I, . E, P. D, copropor phyrin, Y% - 18 8 12 32 coproporphyrin, Y/24 315 106 224 288 .! ! i j It is evident that of 11 patients with benzine poisoning 7 gave porphyri`nuria (36.6Z) and that as regards the workers from the G, Dimitrov State Rubber Plant out of 18 examined 4 (22.2%) gave a high quantity of porphyrin in the urine. These data also were verified statistically. It turns out that for the patients with benzine poisoning the percentage of positive cases varies between 20.5% and 100%. It is interesting that in the workers, although in a very small percentage, disturbance of porphyrin metabolism was established. Such a finding shows how sensitive the indicator investigated by us is. 7 DUP050058720 Conclusions 1. Coproporphyrinuria is a sensitive and very frequently encountered in dicator in occupational poisonings. It gives information about slight damage of the liver. 2. The hepatic tests of the blood used up to now in clinical practice [Weltmann, MacLagan, Gross, Takata-Ara and cadmium test] and urobilinogen and urobilin in the urine give a positive result in very advanced and very severe damage of the parenchyma of the liver. 3. In benzine poisoning coproporphyrinuria is much more frequent in patients. It is manifested even in clinically healthy persons who have been In contact with benzine vapors for a long time. 8 DUP050058721 REFERENCES 1. Bakalov, D,: News of the Department of Biological and Medical Sciences, Bulgarian Academy of Sciences, Vol. 3, p. 97, 1959. 2. Bakalov, D.: Khigiena, Vol. 2, p. 59, 1963. 3. Bermann, I.: Porfirica Choroia, (Porphyria.) 1960, p, 48, 4. Gusev, M. I.: Oigiena i Sanitariya. (Hygiene and Sanitation.) 1959, p. 7, 5. Eberhard, G.: Lehrbuch der phaiologischen Physiologic. (Textbook of Path-* ological Physiology.) 1912. 6. Lehnarfcz, E.: EinfUhrung in die chemtsohe Physiologic. (Introduction to Chemical Physiology.) 1959, 7. Leuthardt, F.: Lehrbuch der physiologischen Chemie. (Textbook of Physio- logical Chemistry.) 1959 r 9 I .1 DUP050058722