Concentrations of Phenol, O-Cresol, and 2,5-Xylenol in the Urine of Workers Employed in Occup Environ Med: First Published As 10.1136/Oem.51.5.354 on 1 May 1994

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354 Occupational and Environmental Medicine 1994;51:354-356 Concentrations of phenol, o-cresol, and 2,5-xylenol in the urine of workers employed in Occup Environ Med: first published as 10.1136/oem.51.5.354 on 1 May 1994. Downloaded from the distillation of the phenolic fraction of tar

Grazyna Bieniek

Abstract high temperature phenolic fraction of tar Phenol (87.3 mgal), p-cresol (58-6 mg/I), (carbolic oil) and exposed mainly to phenol, o-cresol (76.9 mgl), and 2,5-xylenol (36-7 cresols, xylenols, and other phenolic deriva- mg/) were detected in the urine of work- tives. Control urine specimens were collected ers employed in the disttion of the from 26 male subjects not exposed profession- high temperature phenolic fraction of tar ally to phenol, cresols, or xylenols. All men (carbolic oil). The concentrations of were smokers. these compounds in the urine of non- exposed male workers was 11-7 mg/l, 25 7 URINE SAMPLING mg/l, 68-1 jug1l, and 69 ag/l respectively. Urine samples were collected as follows: (1) The excretion rates were 4*20 mg/h for voids collected after four hours at work phenol, 2*4 mg/h for p-cresol, 3.3 mg/h (examined directly after the and of the work for o-cresol; and 1*5 mg/h for 2,5-xylenol. shift) from exposed male workers and non- The highest concentrations of the men- exposed subjects. (2) Successive voids, col- tioned compounds were detected in urine lected for 24 hours from 16 exposed male collected between eight and 10 hours workers. from the beginning of exposure. The kinetics ofexcretion are considered. URINE ANALYSIS The concentrations of phenol, p-cresol, (Occup Environ Med 1994;51:354-356) o-cresol, and 2,5-xylenol in the hydrolysate of urine were determined spectrophotometrically Phenol is a normal constitutent of human after separation by means of thin layer chro- urine1 2 and concentrations above the physio- matography on polyamide gel with the devel- logical level have been found in the urine of oping solvent chloroform-methanol (99:1 people that have contact with benzeneA or V/V).l4 The concentrations were corrected for phenol.56 pCresol also occurs in the urine of a specific gravity of 1-024 and for creatinine non-exposed people and its concentration can concentration in the urine. http://oem.bmj.com/ reach 50 mg/I.7 Small amounts of o-cresol Because of the low concentrations of have been detected in the urine of workers in o-cresol and 2,5-xylenol in urine of occupa- contact with toluene.>" tionally non-exposed workers, gas chroma- After exposure to p-xylene, 2,5-xylenol was tographic techniques were used for these found in urine." compounds. Because high concentrations of o-cresol and 2,5-xylenol were found in hydrolysates of STATISTICS

urine from workers in a carbochemical plant, Geometric mean and geometric SD were cal- on September 28, 2021 by guest. Protected copyright. measurement of excretion of these com- culated. Toxicokinetic calculations were made pounds in successive portions of urine col- according to the methods of Piotrowski."5 lected during 24 hours was undertaken. Results Materials and methods The metabolite concentrations were assumed The investigation was carried out on 106 male to distribute log normally. Table 1 gives the workers employed in the distillation of the concentrations of phenol, p-cresol, o-cresol,

Table Concentration and excretion rate ofphenol, p-cresol, o-cresol, and 2,5-xylenol in urine Value correctedfor Urinary No of Observed value Excretion rate metabolite Group subjects (mg/i) Creatinine (mg/g) Specific gravity* (mgll) (mg/h) Phenol A 89 67-8 (2-483) 38-2 (2-212) 87-3 (2-182) 4 20 (2-281) B 26 13-8 (1-604) 8-3 (1-531) 11-7 (1-486) 0-53 (1-876) p-cresol A 106 54-3 (1-722) 32-5 (1-784) 58-6 (1-841) 2-43 (2 064) B 26 28-2 (1 514) 17-8 (1-515) 25-7 (1-430) 1-32 (1-785) Department of o-cresol A 77 58-9 (3 031) 38-8 (2 243) 76-9 (1-614) 3-31 (2 204) Biochemistry and B 24 75-0 (1-684)t 62-2 (1 594)t 68-1 (1-567)t 3 75 (2 862)t Biophysics, Silesian 2,5-Xylenol A 64 30-4 (2-775) 17-4 (1-720) 36-7 (1-614) 1 50 (1-794) Medical Academy, 41- B 15 79-1 (2-636)t 54-5 (2-366)t 69-0 (2-178)t 3 92 (2-263)t 200 Sosnowiec, Poland Values are geometric means (geometric SD); A = workers employed in the distillation of carbolic oil; B = non-exposed male G Bieniek workers. Accepted for publication *Specific gravity of urine 1 -024. 25 October 1993 tValues in #g/l, ,sg/g, #g/l, and pg/h for o-cresol and 2,5-xylenol in non-exposed workers. Concentrations ofphenol, o-cresol, and 2,5-xylenol in the urine ofworkers employed in the distillation of the phenolicfraction of tar 355

and 2,55-xylenol in the four hour samples of Discussion urine ifrom the workers and non-exposed Considerable differences in the concentration

subject,S. of vapours of phenolic compounds at various Occup Environ Med: first published as 10.1136/oem.51.5.354 on 1 May 1994. Downloaded from The:necessity to use hydrolysates of urine is sites of the work area, difficulties in defining evidenc-e that the compounds are excreted in time of the exposure of particular workers, urine ira the form of conjugates, probably as and likely absorption of phenolic compounds glucuro)nides and sulphates. through the skin are reasons why measure- In 1 (6 workers employed in the distillation ment of the mean metabolite concentration in of cartbolic oil, the excretion of phenol, the urine seems to offer the most rational o-cresol1, and 2,5-xylenol in successive voids of solution for realistic estimation of exposure. urine c-ollected during 24 hours was deter- Technologically processed carbolic oil con- mined. The highest concentrations of pheno- tains phenol (14%), o-cresol (4 8%), and 2,4- lic comr pounds were found during the first two and 2,5-xylenol (1 8%). High values for con- hours after the end of the work shift. centrations of phenol, o-cresol, and 2,5- The urinary excretion of phenol, o-cresol, xylenol in the urine confirm that exposure to and 2,!5-xylenol as a function of time from these compounds occurred. Because o-cresol the be,ginning of exposure was examined has been detected in the urine of persons mathennatically. The elimination of phenol, having contact with toluene12 high concen- o-creso.1, and 2,5-xylenol in the urine of work- trations of o-cresol in the urine of the workers ers can be described by the equations shown might be the result of their exposure to both in the fifigure. toluene and o-cresol present at the workplace. Because of considerable fluctuations in the For technical reasons, the data on urinary concern tration of p-cresol in urine of non- concentration of the phenolic compounds are exposesI persons, the excretion ofp-cresol has not accompanied in this series of investiga- not been considered here. tions by counterpart data on their concentrations in the air of the work premises. The data suggest, however, that in the absence of data Urinary excretion as a function oftime. (A) 120 _A on air concentrations, the determination of phenol; regression equation .. phenolic compounds in the urine may be valid t < = . . . as a comparative test of exposure. for 8-8, c(t) 105 0, (I-e-1 11011))Jor t > 8-8, E 90 _ *. . * Th~~~~~'e similar shape of the excretion curves c(t) = 105 (l1_e-0 16(t+l,,e-0 16(t-8-8) . presented in the figure suggests similarities in k = 0-161h, t,,2 = 4.3 _**../ ' the metabolism of these phenolic compounds. hours. (B) o-Cresol; .5= 60 j* .* .- i\ a'The phenol, o-cresol, and 2,5-xylenol regression equationfor C excretion curves found under conditions of t = 62-68 <8-8, o(t) .. *" a are (l-e-0346t-l));jor t > 8-8, -C7, 300 , Em exposure in carbochemical plant similar c(t) = 62-68 (1-e-034(t')) 0- . to the curve obtained by Piotrowski'5 after e 034"t8-)); k = 0-341h, t,12 experimental exposure of humans to phenol. = 2-0 hours. __i_ With regard to phenol itself, the fit of the (C) 2,5-Xylenol; regression http://oem.bmj.com/ equationfor t < 8 4, c(t) 0 2 4 6 8 10 12 14 16 kinetic curve is only approximate. The real = 85-6 (1-e-"023!;for r > values suggest a more prolonged process of 8&4, c(t) = 85-6 (I-e-0239 e-0 23(t-84); k = 0-231h t,12 = B elimination, a phenomenon discussed earlier 100 hours. I by Paradowski2 in the case of workers with 3-0 CD c = concentration of E longstanding exposure to aromatic com- compounds in urine; t = 80 Such excretion does not timefrom start of exposure. pounds. prolonged Note: o-cresol and cC occur in volunteers not previously exposed to 60 2,5-xylenol were not found _ . . aromatic compounds (unpublished data). on September 28, 2021 by guest. Protected copyright. in some urine samples in . With this reservation in mind the studied phe- which phenol was found. Co 40 Hence there are fewer a, nolic compounds are characterised by high points on graphs B and C 0 ._ / \ * turnover rates, which principally exclude their than on graph A. 6 20 possible accumulation in the course of subse- *______quent days of exposure. 0 The kinetic results presented here show 0 2 4 6 8 10 12 14 16 that phenol, o-cresol, and 2,5-xylenol are quickly excreted into the urine. Thus the I C results of the biological monitoring relate to 100 _ * * on the of urine collection rather E0e exposure day 1U than on the preceding days. a, 80 .5c 80 60 I thank Professor JK Piotrowski for his assistance in kinetic 60 calculations, and Professor T Wilczok for the a,c supervising ) work. I am grateful to K Klimek MS for her help with 40 statistical analyses. 40 x 20 Ls 20 1 Dutkiewicz T. Evaluation of benzene exposure using the 0 1 I ' phenol test in industrial conditions. Med Pr 1965;16: 0 2 4 6 8 10 12 14 16 25-30. (In Polish.) 2 Paradowski M, Jakubowski M, Podoski M. Toxicokinetics Exposure of benzene in man: excretion of phenol in urine and of benzene with expired air after single and 4-d exposure to Time (h) benzene. Med Pr 1984;35:85-96. (In Polish.) 356 Bieniek

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