Document wqQ3Yy4gZOKoJZvNmjaYG3Qpd

IHorizons - Biological Monitoring V: Dermal Absorption Vera Fiserova-Bergerova (Thomas), PhD J. Thomas Pierce, PhD ... Chemicals believed to have the potential which was estimated to average 1.8m2 for hr).I 1-'3) The penetration rate depc for significant dermal absorption are listed a male and 1.6m2 for a female (male: 70 kg. the vehicle and sate ofaggregation& in the 'IhresholdLimit Values and Biolog- 170cm;female: 58 kg. 160cm).'') the chemical is applied. Skin ink ical Exposure Indices for 1988-1989 booklet with a skin notation.'l) Since there are few means available to monitor dermal exposure using external measurements, biological monitoring is recommended "to determine the relative contribution of der- Chemicals can penetrate through the stratum corneum and diffuse into the dermis where they enter into the capillap blood. The chemical is then carried by sys- temic circulation to other tissues where it is deposited, metabolized. and excreted.I8) Creases the p e n a m i o n rafe. Percutaneous penetration is a 1 diffusion process mediated by two*; ways: intercellular (polar) pathw; transcellular (lipophilic) pathwq Penetration rates for both pathways. mal exposure to the total dose" that the The rate limiting step in dermal absorption r e d y related to solubility of the ch worker received during occupational ex- is either the penetration rate through the in water and lipids and indirectly \ posure to chemicals with a skin notation.' I ) Since systemic adverse effects are related to biological levels of the chemical or its metabolite. or to the total dose. biological monitoring is. under cenain circumstances. 3 bener safeguard than air monitoring stratum corneum (uptake rate) or the rem o d rate of the chemical from the dermis (absorption rate). Both processes are intluenced by physicochemical propenies of 'the chemical. namely biosolubility, and by physiological status of the slon. lecular weight. Numerous m d proposed for determining fluxfron i d propenies of the drug. These P arecently critically reviewed by can be applied to the prediction c absorption potential of industrial I data. Quantitative data on dermal absorption of industrial chemicals are scattered and dermal notations are inconsiSfent.(2J)In the absence of inhalation exposure. significant concentrations of exposure indices were measured in blood. urine, and exhaled air of volunteers having dermal contact with liquid solvents which carry n o skm nom- The absorption rates relate directly to blood perfusion of skin. Perfusion in- c r m with the temperarure of the environmenr a n d physical activity of t h e worker.'9) Since cardiac output increases in a similar manner, it can be assumed that perfusion of dermis accounts for about 53 percent of cardiac output and perfusion of the hvpafermis for about 2.5 percent. c3k (organic n o n e l e ~ o l Y ~ ~ ) . fwdel providing r a n a b l e P r d flu* I" can be described by the tali equation: -FI = CS.31 (0.038 15 + 0.153 P)e-OOISMw where: 1 : *- tion.l+-b)These studies indicate that a con- FI = flux in mg/cm2ihr tribution of dermal exposure to the total dose is more common than is indicated by a skin notation. ' Mechanism of Dermal Absorption Skin is formed by layers o f various cell ~ p e swhich. according to their composition m d function. are identhed as the three Flux The stratum corneum functions as a diffusion barrier. The penetration rate of a chemical through the stratum corneum is known ;LT tlux. Flux is defined as the m o u n t of a chemical ( mg or pnol) that penetrates the stratum corneum upon direct contact with a defined unit of surface area of skin c, = the concentration of satu aqueous solution of the in mg/ml *.. = ocranol-\lc.ater panition coem kIvc' = molecular weight e = ba5e of [he natural l o e r i h Numerical constants are derived p rameters pertinent to the diffusion p y x basic layers shown in Table 1. Thickness of (cm') during a defined unit of time (min. through the stratum corneum. The the layers, their weights. and perfusion are given for 3 resting reference human with a body weight of 0' kg, body height of 10' cm, and cardiac ourput of 6 L'min. The numbers are mean values which vary from TABLE 1. Diagram of Skin Layers Thickness, Weight m9 Perfusion, Umin c one pan of the body to another. If two numbers are given. the first value relates stratum corneum dead cells llvlng cells 10 40 100.90 0 +;'" to males m d rhe second to females.'-) Dermis proteins. blood cel; 1250 2500.1700 02 'lL" I The surface area of the skin can be considered as cqual to body surface a m (SA). 614 Hypodermis connective tissue fat (adipose tissue) W 8 2 - ~ 1 4 4 5 $ 2 'D. 1~909 AIH 1 3 7 5 W 7500.13000 0 15 .& *-Y APPLIED INDUSTRIAL HYGIENE i4t8 * nential expression in equation 1 indicates that the flux of chemicals with large molecules is negligible. A molecular weight of 500 has been given as a practical limit, al- though this may not be the case for dis- eased skin.' In oihp flux can be determined experimentallv by measuring the diffusion rate across an excised section of stratum corneum.(16J7)Flux can also be determined in ttitlo either by measuring the losses of' a chemical which has been hermetically applied to a defined area of the skini5'or by measuring the elimination of the chemic31 and its m e t a b ~ l i t e s . ( ~ . ~T. Ih~e Jr~es'ults of measurements depend on the method employed. Values obtained by measurements of elimination should be cautiously applied since the pharmacokmetic pattern for dermal absorption is rarely fully ap- preciated. Because of regional variations in skin permeability. the measurements depend on the region where chemical con- &a with the skin took place.'11' Regional variability in can be attributed to cell sion rate. Significant spe in dermal penetration ported.'20' If the chemic vehicle (solution,air. ointmen etration rate depends on the tion and solubility of the che vehicle.' ! I ) The wide spread of mentally-determined pen a.p.parent from examples c o m p i 1 4 & Table I1 (column Flm& TABLE II. Dermal Absorption Potential of Chemicals with BaS Predict nv nv mg/w MW LogP H20 sol. WmI L (Ref.) - fl fl* Nonvolatile (9 e 5 torr) e x Aniline 10 93.1 0.90 34.0 0.5 (23) 0.64 3.0 (24) 0.0075 e x DMAC 35 87.1 -0.77 943.0 1.00 0.026 o x DMF 30 73.1 -1.01 944.0 2-8 125) 1.03 0.023 ox ex Furfural Nilrobenzene 8 96.1 0.99 83.0 5 123.1 1.85 1.9 0.2 (19) 9 x lo-' 112) 0.2-3 (26) 1.82 0.19 0.W 0.004 o x Parathion 0.1 291.3 3.81 0.024 0.6 (27) 0.015 7x l(r o x PCP 0.5 266.4 5.01 O.OO08 0.012 O.ooo4 e x Phenol o x Styrene 19 94.1 1.48 67.0 215 104.0 2.95 0.30 0.004 (12) 0.2-0.7 (23) 0.03 (32) 0.06 (18) 12.0 (33) 4.62 0.52 0.014 0.161 Volatile (SVP : 5 lorr) 0 Benzene 30 78.1 2.13 1.78 2.8 0.19 (32) 0.70 0.022 ex Carbon disulfide 30 76.1 2.00 2.94 0.8 0.05 (28) 0.89 0.022 Chlorobenzene 350 112.6 2.46 0.50 41 0.24 0.26 3 Ethyl benzene 435 106.2 3.15 0.20 0.06 (32) 17 0.16 (29) 0.53 0.33 28 (29) 0 n-Hexane 180 86.2 3.94 0.014 1.1 6 x lo-' (32) 0.31 0.14 o x MY1 alcuhol 260 32.0 -0.77 791.0 1900 8.3 (12) 11.5 (30.31) 2.02 0.195 0 Methyl chloroform 0 MEK 1900 133.4 2.49 4.4 590 72.1 0.28 353.0 0.93 0.37 (32) 1.64 1.42 254 2.45 0.44 Perchloroethylene 335 165.8 2.60 0.40 0.43 0.005 (32) 0.11 0.24 (32) 0.25 0 Toluene 375 92.1 2.69 0.60 2.2 0.047 132) 18 (5) 0.69 0.28 0 Trichloroelhylene 270 131.5 2.29 1.10 1.5 0.27 0.20 i0 0.006 (32) Xylene 435 106.2 3.14 0.18 1.7 0.13 (33) 0.50 0.33 - - -! 70 (5) N01eS: MW = molecular m g h t log P = iogarilhm 31 octanol-der partition cOellicient H?OmI = saturated aqueous sotuiion = Nater-gas paartition coellicient F,I = axperimtally determined HIM (rdetma are in wmthesis) FI = fluvdicted using eauation 1 FI' = uitical !lux as determined by equation 5,'IF = critical flux lor dermal absorption 31 vapon 'eauallon 7) svmbol 3 ' On ihe let side 01 Ihe :able indicates the dermal absorption potmtlal Mi$ indicates dermal ioxicily potential (see text). x indicates skin notation In TLV-BE1 booklet 'I1Bold number indicates dermal absorotion p~tentlalor vawr F-16 4PPliED lNDUSTRlA1 HYGIENE WE I f Q HI-3600 New instrumentationfor measurement d non-ionizingradiationfrom video display terminalsand accurate measurementsof power fmquency EMF (Electricand MagneticFields) from electric power lines. 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Site License - .-_. -P $299.95 ORDER THE EQUALIZER Dbase TODAY! $495.00 CALL 1-800-225-5669SEVEN DAYS A WEEK. MASTERCARD OR VISA, P.O. & CO. CHECK. DATACHEM, WESTBORO, MASSACHUSITS Requires 2 (7ZOk) a I1 D ,3404 DOS LO+,WXTIAT or eomphbk (also available in 5 114") Qrrlr&Dmoam 116 Dermal Absorption in TABLE 111. Factors Affecting Dermal Absorption Industrial Settings The amount of dermally-absorbed chemi- cal is directly related to exposure duration and surface area of the exposed skin, and it is affected by the form of the chemical contacting the skin. Since dermal and pulmonary absorptions are pharmacokinetic I Physicochemical piopeflies of the chemicals solubility in: water nonpolar solvents dilfussion coefficient molecular weight Eft* Grading processes, the absorption rate changes with volatiliy time. Moreover, dermal absorption is affected by the physical acti\lieof the worker. namely by the skin temperature and increased perfusion of the dermis in the exp o x d area of the skin.(*,21)Factors influencing the absorbed amount are summarized in Table 111. Form of Chemical Dermal absorption in an industrial setting can occur upon eqo..ure to raporsor upon direct dermal contact with liquid chemicals or with their solutions. Condensation of vapors of chemicals with low vapor pres- II Physiological and anatomical parameters of the exposed skin thickness of the stratum corneum hydration of epidermis perfusionof dermis lipid content in external layers of skin disease state of skin 111 Form of exmure exposed area of skin duration of dermal exposurec state 01 aggregation vehicle: concentration in vehicle solubility in vehicle environmental temperature humidity physical activity of the worker exposure by other routes (intensity and duration) 1 fi t _-8 -._- ?l . ,- ll tt n L t t t sure o n the body surface can significantly incre3se dermal absorption of vapors."9) Dermal absorption of solids (dust, aero- sols, etc.) can be facilitated by their dis- solution in perspiration. The dermal pen- etntion rare of dissolved chemicals appears to be directly related to their concentration and indirectly to their solubility in a solvent. A prolonged contaa with liquids usu- Pharmacokinetic Considerations ally results in biochemical changes in skin Penetration rate (flux)through the stratum m d skin permeability.' i3' corneum is influenced by the physiological Chemicals Exposed Area of Skin While the surface area o f skin exposed to vapors, gases, and aerosols usually corresponds to the body surface area, the surface area of skin expo& to liquids is difficult to estimate. In an industrial setting, the area of body surface exposed IOliquids usually accounts for only 3 small fraaion of body surface, S A Hands are usually subjected to exposure to liquids. It was estimated that the surface area of one hand ( u p to the wrist) accounts for 2.5 percent of S A , and the area of an outstretched palm and fin- status of the skin at the exposed area. Certain changes in the penetration rate usually 3 p p m at the beginning of the exposure during 3 soalled lag-period.">' During W lagperiod the concentration buildup in +e epidermis and dermis rakes place. At the same time, the mast significant biochemical changes in the stratum corneum are induced by contaa with the chemical. 0therwise, the penetration rate, under stable dermal exposure conditions, remains constant. On the other hand, the absorption, Le., the transfer of the chemical from the dermis into capillary blood. is a diffusion There are three slmilarities ~n the hnetic pattern of inhalation and exposures. 1 The absorption rates are diffusion of chemicals cellular s t r u m r e of par sues and are related'to b i c & q , %1. In ;u1 industnal setting, both s u r a are enduring. *.,. .+ 3. The absorbed amount is equaq;&c persed in the entire crrdiac oucpr p r i o r to e n t e r i n g circulation. the syste.q~.$.@.&. C gers accounts for 1 percent of SA") The process dependent on the dermis-blood The interaction between dermal id area exposed to dust or aerosols can ac- concentration gradient and the diffusion pulmonary absorption is apparent i f t k *count for 3 large fnction of body surface. coefficient itself. Since concentrations of studied chemical is 3 gas or a volatile Spills or contaminated clothing c m also the chemical in the e?rposed dermis and i d . moderately soluble in blood (* result in exposure of a large M y surface. blood rise at different ntes, the dermal ples are hydrophobic organic solvena) Duration of Exposure eabsorption rate is 3 h n a i o n of time.(*.") These chemicals, when absorbed d e n n a b The absorption rate is affected not only by are p a ~ l Vremoved in the lung by The duration of dermal exposure to va- the dermal rate but also by the supply of tion,' 4-6. 21 Consequently. the dermal--* pors, aerosols. and dust can be considered the chemical from other routes. of which sorption reduces o r suppresses the pd. equal to the length of 3 shift. On the other inhalation is the most common in indus- m o n a r y u p t a k e p r i o r to making hand. the duntion of dermal contact with trial settings. When the uptake and elimi- contribution to the body burden. ThW* b wliquids or solutions depends on the work- nation prcxesses approach steady state, dermal uptake of volatile chemical ing process involved and the personal skills dermal md pulmonary absorption mtes ue effect o n biological levels than d e d ' l p and hygiene of the worker. F-18 more o r less c o n s m t and time indqxmdent. '* Itake of nonvolatile chemicals. H e ..&i*. APPLIED INDUSTRIAL HYGIENE I4B * I DataChem Uormerlv UBTL. 1nc.l OTECTION %5f Hghly Motmtional How the Ear Works Latest Auditorv Research Sensorifleural Hearing Loss Proper Protection Covers OSHA Standards I I I j I I i &It Lake City (Sol)266-7700 1-800-356-9135 -2.*c:-.Cincinnati (513)733-5336 1-800-458-1493 hreshold Limit Values +.w._a-nd Biological Ex osure B-&: Indices for 198 -90 Be sure to order your booklet today! ..r, -.-;A&dbosptatetidcesarairdidpprloiwpoicsaeldagTeLntVss for over 700 cheiiiica[ Biological Erposiire Indiccs -io1 1988 ACGIH Policy Statanent on iise of TLVs -ptkgal staiidardr - p i a ! 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Criteria for significant dermal ab- that the concentration of the chemical in the epidermal water is equilibrated with the concentration in the ambient air: Constants for prediction of flux us1 a n be found in references 34-39. panition coefliaentscm be found UI sorption potential can be selected arbitrarily, depending on which effect of dermalabsorption is under consideration.Thus, we CM decide that biological monitoring FICaD= -EA FL' -loOOc,t SA TLV A where: References 1. American Conference of P.-..5- of inhalation exposure is appropriate only if the absorbed amount of chemicals does not exceed 30 percent of the pulmonary uptake during an occupational inhalation exposure to the threshold limit value-time weighted-average (TLV-"A), or if dermal absorption of volatile chemicals does not increase the arterial blood concentration 30 percent above the mncentrarion reached during occupational inhalation exposure to the TLV-'IWA(22) The hvpothetical flux, which meets this criterion, is further referred to as critical flux. FI'. Critical flux can be determined by comparing the dose resulting from inhalation exposure to the TLV-WA with the dose resulting from the same inhalation exposure but with additional dermal exposure of a defined area of skin. We arbitrarily chose to calculate critical flux for exposure of 2 percent of the body surface to a liquid and for whole-body expasure to a TLV concenmtion of vapors. Thus. during inhaiation exposure only, the dose. D, is equal to pulmonary uptake: SA = body surface ( = 18000 cm2) C~ = saturated aqueous solution of the chemical in mdml A = the appropriate water-gas parti- tion coefficient The expression obtained after substitution indicates that the critical flux for vapors depends only on the solubility and volatility of the chemical. To evaluate toxicity potential of dermal absorption, we used the algorithm described above, but w e arbitrarily assumed that [OXicit). is associated with tripling the dose and biological levels. Such critical fluxes, FI" and FI", respectively, are described by the following equations: FI" = 5 TLV and (8) dusrrial H g ~ e n i s t s :Thres and Biological Exposure Indices for 19eg 1989. ACGIH. Cincinnati, OH (1%). 2. Grandjean, P.; Berlin, A; Gilbert, M; ning, W.:Preventing Percutanew tion of Industrial Chemicals:'Ihe % notation. Am.J. Ind. Med. 14:97-107 ( I i 3. scanseni. G.;Piolatto, G.; R u b h , &&, Notation in the Contexr of W 0 r k p k . b posure Standards.Am. J. Ind Med 14- 732 (1988) -5. p<- - 4. S t m , RD.; Dodd. H . C . : A b ~ p t i ~ & . bon Tetrachloride. Trichloroechykn. R. trxhlororrhylene. Methylene C h l e 1.I .I ,-TrichloroethaneThrough the Skin. Ind. Hyg. J. 25:439-146 (3964). 5. Dutkiewia, T.; Tyns, H.. Skm Absorprbad ---_Toluene, Styene. and Xylene by MaR &J Ind. Yed. 25243 ( 1968). 6. Site. A; Nakaiima. T.:Differences-F Skin or Inhalation Exposure in the tion and Excretion Kinetics of -T thylene and Toluene. Br.J. Ind. M e d .. 49 ( 1978). -. Repon of the Task Group o International Commission Protection No. 23, p. 54. N e w York f 1974). 0 = Vaw (TLV-c,) T (2) The potential for dermal toxiciy can be overestimated if the TLV is based o n irri- and during simultaneous inhalation and tation or discomfort. dermal exposures at which the dose and biological levels increased by 30 percent Dermal Absorption Potential of 1.3 0 = \jaw(TLV-1.3 caw)T + FI' x EA x T (3) Chemicals with 8Els Orgmic chemicals for which BEIs dre rec- where: ommended a r e listed in TJble 11. The table lists the parameters used for calculation of V h = alveolar ventilation in Uhr tlux and c r i t i d flux. Dermal ab.sorprion cdv = alveolar concentration in mgL T = e.xpasure duration in hours can significantly intluence the biological levels if the predicted flux is larger than EA = exposed surface in cm2. the critical flu. FI'. Such dermal absorp- tion potential is indicated by "0" on the After substituting from Equation 2 into left side of the table. Chemicals with the "*".Equation 3, the equation can be rearranged dermal absorption exceeding FI" are in- to c3lculate the critical flux: dicated by Chemicals with such exten- FI* = 0.3 x TLV EA x V,,, sive dermal absorption usually carry a skin (4) notation in the TLV table ( i n Table I1 indicated by "x"). 8. Guy, RH.; Hadgtaft. J.: cumeous absorption ' prmch. Toxicol. .4ppl. ( 1985). 9. Bunon. AC.: Physiology and Biophysiq'd the Circulation. pp. 13-22. Year Boa&&& ical Publishers. Inc.. Chicago. IL (I-' 10 D u p d . P.H.:Skm P e r m e a b i l i y n K o y k h lation to I\leasuremen:nrsof Percu-, .iorption in Toxicology. In D e r m a t w 0p;y. 3rd ed..F.N.Yarzulli and H.I. E&.. pp. 525-550. Hemisphere Publkt& Corp., Washington. DC (1988). t I 11. Schruplein. RJ.:Permdility of the Skin In Handbook of Ph!siolop. Reactions to Environmental .writs.pp. 299-32Z D.HK LS Ed. .\rnrrican Physiological Society. Be- [I .i rhesda. MD ( 19-l 11. Schaefer.H.: 2esch.h. Stungen.G.: F b . ~ Skin Permeability. pp. 829-831. Sprir\gs- V'rrlag, New York f 1982). 13. Dugard. P.H.. Scw.RD.:;\bSorpUOn ThrouBzI Skin. In: Chemotherapy of Psoriasis. H.P. After substituting Valv = 900 Lrhr and EA = 360 cmd, the critical llux (expres.wd in mg/cm2/hr)c m be related to the TLV (expressed in m./Z) bv a simple expression: FI' = ;3iTLV (5) Similarly. critical llux for whole body exposure to vapors can be derived. xssuming The notation of dermal absorption potential is not necessarily an indiator of increased health risk. It indicates, however. that the correlation between Lir me-surenirnt5 and biological me;lsuremenu can be weakened or nonexiaent. L'ndcr such circumstances. biological monitoring provides information on total expcmre of a o r k e r s and not o n inhalation exposure in the workplace. Raden, Ed.. Section I10 of Internatid cyclopedia o f Pharmacology and t i a . pp.125-142. Perpmon P ~ ~ S So.d d England 19%). 1t. Oshomr. D.W.. Cornputxional Methods Prcdiaing Skin Perrneabili? P h i i d al ManufaauringTechnical I.'p&te. Pp.41- *4- ('piohn Co. c.qril 19%). l i Ijerner. G..Cooper. E.R. MMtxieIs of P1.rmCJbilin'. In: ~nnsciermaD~ eliVal d D N ~ S .Val. 11. pp. 41-55. h F KvdonieuSd I F-20 L uAPPLIED INDUSTRIAL HYGIENE 14n CRC Press, Boca Raton. FL Toxicology Ltrs. 10367-372 (1982). 34. Leo, A;Weininger, D.: Medchem Softuve 25. Maxfteld, M.E.; Barnes.J.K;Azar, A; Trochi- Release 3.33.Medicinal Chemistry Project, H.: percutaneous Absorption of Or- mowia, H.T.: Urinary Excretion of Metab- Pomona College. Claremont, CA (1985). Method for Measuring olite Following Experimental Human Ex- 35. Hansch,C.;Leo.A: Substitutent Constanrcfor of Chlorinated Solvenrs posure to DMF or to DMAC.J. Occup. Med. Correlation Analpis in Chemistry and Biol- Rat Skm. Ind Health 15131- 17:506-511 (19-5). ogy.vl'iley-lnterscience Publishers, New York 26. Salmowa.J.; Piouowslu, J.: &tempt on the (1979). u.:.MawdSley,SJ.; scoct, Quantitative Estimation of Nitrobenzene Re- 36. Leo,A;Hansch, C.;Elluns,D.: Partition Coef- Some Glycol Ethers sorption in Expenmental conditions. Med. ficients and Their Uses.Chem. Rev. 71:525- V i b o .Environ.Health F%q. 11:l-14 (1960).(in Polishi 616 (1971). 7:193-197 (1984). 27. Fredriksson, T.: Studies on the Percutaneous 37. Verschueren, K:Handbook of Environmen- Ea;-, M.; Droz. P.O.; Guillemin. M.: HU ipa rxpoSure to Spiene. VI. Percutaneous .vi ''&uxprjon in Human Volunteers. 11-11.Arch. Absorption of Parathion and Paraoxon. 111. tal Data on Organic Chemicals, 2nd ed.Van Rate of Absorption of Parathion. Acta Derm. . N m d Reinhold Co., New York (1983). Venerol. 41:353-362 (1%1). 38.The Merck Index. An Encyclopedia of Chem- '?&sup. Environ. Health 55:331-336 ( 1985). 28. Baranouska. B.: Emluation of Skm Absorp- icals and Drugs. 9th ed. M. Windholz, Ed. : The Absorption, Metab tion of Carbon Daulphide. Int. .kchiv. Gew- Merck & Co.. lnc., Rahway, NJ(1976). n of Furfural in Man. Int. erbepath. Gewebehyg. 21:362-368 (1%5). 39. lange's Handbook of Chemistry. 12th ed.. iron. Health 41:159-168 (in German) JA. Dean, Ed. McCnw-Hill Book Co.,New 29. Dutloewia, T.;Tyas, H.: A sN& of the Skin York ( 1979). S w ,RC.; Maibach. H.I.: PercutaneousAb- .*--: in Man and Animal: A Perspecuve. Toxicity pp. 1 1 1-126.V A Driu .Eds Academic Press. Inc New Absorption of Ethylbenzene in Mm. Br. J. 40. Fiserova-Bergerova,V.: Gases and Their Sol- tnd. Med. 24:330-332 (1%:). ubility: A Review of Fundamentals. In: Mod- 30. Durkiewia, B.: Konczalik. J.; Karwacki, W.: eling of Inhalation Exposure to Vapors: Up- Skin .4bsorption and Per Os Mministntion rake. Distribution, and Elimination. Vol. 1. of MethYlol in Men. Int. Arch. Occup. En(Thomas),V Stmula- viron. Health 4?81-88 ( 1980). sorption of Organic Sol- 31. Sedivec.V.; Mraz. M.;F1ek.J.:Biological Mon- +p ~3-. 28.V. Fm-Bergerov?.Ed CRC Ras. 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