Document 6ebG5XNzdnyp1p7Jwr7J99pE

c c o l ~j work environ health 8 (1982) 169-177 Occupational exposure to arsine An epidemiologic reappraisal of current standards f sy Philip J Landrigan, MD, MSc, Richard J Costello, PE, CIH, dilliam T Stringer, MS' The interpra in biology. 79, chapter 7. adels and SOU- demiol 43 Interaction n J epidemioi i# Y y and estimatfqj Xm J e p i d e w 1! F Confound& Am J e p i d e q id antagonism 44 Am J e p i d e q ition of synerp4l -demiol 103 (1979 I i epidemiol S Walker Am J epide -wergism. h --66 Bootstrappi nalysis of netricb 36 (1 of aisease att !iect of two fa LANDRIGAN PJ, COSTELLO RJ, STRINGER WT. Occupational exposure to arsine: .4n epidemiologic reappraisal of current standards. Scand j work environ health 8 (1982) 169-177. In an evaluation of chronic occupational exposure to arsine (ASH:$), an epidemiologic survey was conducted at a lead-acid battery manufacturing plant. Personal (breathing zone) air samples were obtained for the measurement of exposure to arsine and particulate arsenic (As), and area air samples were also collected for the determination of arsenic trioxide (As.O$ vapor concentrations. For the quantification of arsenic absorption, total arsenic content was determined in duplicate 24-h urine samples. Arsine in 177 breathing-zone air samples ranged from nondetectable to 49 !cg/ma. The highest levels were found in the battery formation area, where arsine is generated by the reaction of battery acid with lead-arsenic alloy. Exposures to particulate arsenic (maximum 5.1 !cg. mY) and to As.O;j (maximum 0.44 !4g/m3, expressed as As) were generally lower. Urine analysis showed that eight (70.5 "'0) of 39 production workers had urinary arsenic concentrations (corrected to a specific gravity of 1.024) of 50 y g l l (0.67 !imol/l) or above, indicating increased arsenic Absorption. None of eight office staff had elevated urinary arsenic levels. A close correlation was found between urinary arsenic concentration and arsine exposure (Pi = 47; r = 0.84; p = 0.0001). Arsine levels above 15.6 !cgim3 were associated with urinary arsenic concentrations in excess of 50 !cg,'l (0.67 !tmol!l). No correlation was found between urinary arsenic content and exposures to particulate arsenic or to Xs-,O:j. Consumption of neither seafood, red wine, tobacco, nor contaminated drinking water accounted for urinary arsenic excretion. It was concluded that the current arsine exposure standard, 200 ceg;m3, fails to prevent chronic increased absorption of trivalent arsenic from the inhalation of arsine. Key terms: arsenic. epidemiology. industrial hygiene. occupational medicine, workplace standards ir:.:!.. gas (.4sH:;) is the most acutely toxic ,r-,: i n o r g a n i c a r s e n i c (10). I n h a l a t i o n ,LL. . r a p i d i n t r a v a s c u l a r hemolysis. i,m,:.xsof h e a d a c h e , d y s p n e a , n a u s e a . .:!d - illiting begin 2 to 21 h after inha- ,.:: I , . I n s e v e r e cases t h e y a r e followed : -.)%: r a p i d a p p e a r a n c e of a n a l m o s t :).,:k ..::omonic clinical t r i a d of a b d o m i n a l -,::: -2rnaturia. a n d j a u n d i c e (15, 27, 31). !) I 1)' -' ., I 1 of Surveillance. Hazard Evaluations id Studies, Ndtional Institute for Oc- Safety dnd Health. Cincinnati. - nlted States q u e s t s to D r P J Landrigan. Division 'Idnce Hazard Evaluations and Field YIOSH. 4676 Columbia Parkway. Cin- iH 45226 VSA Death is caused by acute renal f a i l u r e . a p p a r e n t l y t h e result of massive tubular damage induced principally by the intrat u b u l a r p r e c i p i t a t i o n of h e m o g l o b i n (10). Standards limiting occupational exposure to arsine have, for the most part. been intended to p r e v e n t a c u t e toxicity (1). In the United States, the arsine exposure s t a n d a r d of t h e O c c u p a t i o n a l Safety a n d Health Administration (OSHA) is 200 l/g:rnY, m e a s u r e d as a n 8-h t i m e - w e i g h t e d average (46); t h e guidance in the United K i n g d o m is a hygienic limit of 200 !(g m9 (8). The Scandinavian countries h a v e also adopted an exposure standard of 200 !tg m;!, w i t h the exception of Sweden w h i c h h a s a d o p t e d 50 !rg.'m3 as i t s stan- dard. 0353-31403 82 030169-09USD3.25 Current occupational exposure standards for arsine are not intended to protect against any toxic consequences which may result from chronic inhalation of the gas (4). Chronic inhalation of arsine in concentrations below those required to produce acute toxicity would appear however to be widespread in modern industry. Potentially exposed workers include metal smelters and refiners, metallurgists, solderers, lead platers, battery makers, and manufacturers of semiconductors (10, 45). In such workers, inhaled arsine is rapidly removed from lung tissue (35) and is oxidized to form elemental trivalent arsenic (As':') and arsenous oxide (arsenic trioxide, As,O,,) (10, 2 7 ) . Both of these species of arsenic have been shown to be human carcinogens (26). To evaluate arsenic absorption in workers with chronic occupational exposure to arsine, we conducted an industrial hygiene and medical survey at a lead-acid battery manufacturing plant (25). We found chronic arsine exposure at levels below the current OSHA standard, and we found a strongly positive correlation between arsine concentrations in the air and the urinary excretion of arsenic. Arsine exposures of less than one-tenth the current OSHA exposure standard were associated with the urinary excretion of arsenic in amounts significantly greater than a population norm of 50 ,/cg,l (18). These observations suggest a need for a downward revision of the arsine standard to protect workers against the possibly carcinogenic consequences of t h e chronic absorption oi trivalent arsenic through the inhalatior. o! arsine gas. Background The plant which we evaluated has beer. in operation since 1965. It employs approximately 200 workers and produce.. lead-acid storage batteries accordin; :c conventional technology (fig 1) (48). L e x oxide is produced during the tumbling 0: lead pigs in air in a ball mill. The os:dt is then mixed with sulfuric acid and (1-her minor additives to form a paste, and :i?t paste is applied to grids cast of me7.:ll!c lead. The lead-lead oxide plates are 32sembled into groups, welded toge::er placed in plastic casings, and attached 1' posts and terminals. The assembled batteries are filled with acid, and in the &;tery formation area of the plant u t "formed" electrically by the applic&:!or of direct electrical current. After formation, batteries are either drained ?nc shipped dry or sealed and shipped m i ? acid. Arsenic is used in battery production aan alloy with lead in concentration.< 0: 0.5 to 0.7 O:O (48). The arsenic incrsasrbreakage resistance ("hardens" the l a c and increases resistance to electroche::!Cz, corrosion (41). The introduction of arsenic to ba::er: PURCWASIO LEAD PURCW A SED LEAD AI PURCWASID LIAD flOl*CI -Fig 1. Process flow Lea' acid battery plant, Novem?1980. (* = job category w ' ' potential exposure to 21rb0'" arsenic species) Banufactu lia1 exposL Arsine ma formation comes into may be f ( operations !eased into alloys are senic trios generated alloy. such Methods lndustrza 1 The envirc in the pre; to measure psures to late arsenic centrations survey focL plant areas sure to on appeared t i time of the were emplc areas. To measu Particulate velaped a <, comprised ester filter charcoal tuk 0.2 Ymin (7 train was r w e t and fil that of a cr tctte operat (13)- The cc -rn wer those of the muected ful On each of t h u g h ThL mi on all th to arsel bcted full-s day f c who h &PJ$!'knee gr measu e' triox ? a m comF dI 170 9anufacturing creates a hazard of poten- lulose ester filter pretreated with sodium 1131 exposure to several species of arsenic. carbonate and glycerol (CARB filter sys- .kri;ne may be generated in the battery tem) (5. 7). Development of this system formation process when lead-arsenic alloy was necessary because arsenic trioxide io,T1t'sinto contact with acid (24). Arsine can exist in both particulate (fume) and be formed also in scrap recovery vapor states at normal plant temperatures. L,perations.Particulate arsenic can be re- Earlier studies had demonstrated that 25 into the air whenever lead-arsenic to 90 o of arsenic trioxide vapors pass Jil,l~s are cut or fragmented. Finally, ar- through a conventional mixed cellulose , r n : ~trioxide fumes or vapors may be ester filter and that 4 to 40 " j o through ;,cklrated by the heating of lead-arsenic both the conventional filter and its back- :,ilt>V. such as occurs in welding (7). up pad. The CARB system, by contrast, was shown to be more than 90 O , o efficient Methods in the collection of arsenic trioxide (5, 7). Area air samplers were positioned at six d and o t h e ,te, and t k incl.istrialhygiene survey plant locations that offered a wide range of exposure to airborne species of arsenic. of metaue' ThL, environmental sampling undertaken togeth14ites are &9 attached :n ?he present investigation was intended to measure personal (breathing zone) ex- psures to arsine and to airborne particu- "9'2minb1theed bat-* plant a&: arsenic and to determine area air con- centrations of arsenic trioxide vapor. The .<urvey focused on those job categories and applicatio2 i f t e r forma-.' rained and nipped with plar,t areas where the likelihood of expo.;Ure to one or more species of arsenic dppared to be the greatest (fig 1). At the :Ime of the survey, 42 production workers reduction ag ntrations of iic increaser ;" the lead) itrochemicd \yere employed over three shifts in these are.?s. TI, measure breathing zone exposures to pa:r:culate arsenic and arsine, we devel, lped a two-component sampling train coc:?rised of a 13-mm mixed cellulose : to battery t-s:cr' filter followed in series by a 150-mg charcoal tube operated at a flow rate of J.? min (7). The inlet of this sampling was restricted to provide a casette and filter face velocity equivalent TO :ha: of a conventional 37-mm filter cas- ;e:tt- operated at a flow rate of 2 Lmin ,131 The collection characteristics of this were shown to be comparable to f the conventional method (7). We m!:-cted full-shift breathing zone samples Full-shift samples were collected at each of these locations for each of the 4 d of the survey. All air samples, both personal and area, were collected with personal sampling pumps equipped with automatic flow rate controllers. All samples were analyzed for arsenic content by atomic absorption spectroscopy a t the Utah Biomedical Test Laboratory with a modification of method S309 of the National Institute for Occupational Safety and Health. To evaluate the possibility that plant workers might have been exposed to arsenic in drinking water, six tap-water samples were collected from sinks and drinking fountains at the plant. These samples were collected in acid-washed plastic bottles, to which 0.5 g of sodium ethylenediaminetetraacetate (EDTA) was added as a preservative. The samples were refrigerated and shipped to the same laboratory as the air samples for arsenic analysis by atomic absorption spectroscopy with a hydride evolution technique (36). No drinking water samples were collected elsewhere in the community outside t h e plant. on tach of the 4 d of the survey (Monday thr,-mlrgh Thursday) for all volunteer work- Medical examination ?rs (Jnall three shifts with potential expo- The medical component of this survey sure to arsenic species. In addition we col- was intended to measure workers' absorp- 1ec:ed full-shift sampIes on the day shift tion of arsenic and to correlate absorption day for 4 d from the eight office with exposure to arsine and to other spe- 'low - Lead- nt. November -ategory with 3 to airborne who had agreed to participate as a re"fi.e-'remnceeasgurroeu p. ar e a air concentrations of ars?.r.ic trioxide, we developed a collection YTcm comprised of a 37-mm mixed cel- cies of airborne arsenic. To measure arsenic absorption, we col- lected 24-h urine samples on the second and third days of the workweek (Tuesday and Wednesday) from all production and 171 office workers who had agreed to par- Results ticipate in the air sampling survey. (Makeup samples were collected on Thursday Industrial hygiene s u r v e y Table 1. Per category - and Friday from workers who had missed the previous collections.) Workers were given arsenic-free plastic collection bottles with written instructions for the collection of complete 24-h urine output and for sanitary precautions to be observed during the urine collection. At the conclusion of each 24-h period samples were collected at the plant and shaken by hand until they appeared homogeneous. The volume was measured, and the specific gravity determined by a refractometer. A 125-mi aliquot was taken from each sample and placed in an acid-washed plastic bottle, to which was added 0.5 g of sodium EDTA as a preservative. These aliquots were held at the plant a t 4'C for the duration of the study and were then shipped refrigerated to the laboratory for arsenic analysis. As a quality control measure, two separate 125-ml aliquots were taken from each of 12 urine samples. These duplicate aliquots were separately numbered, and sent to the laboratory with no indication that they represented paired samples. Also, four sample collection bottles were washed in the field with distilled water, and the washings sent to the laboratory with EDTA preservative for arsenic analysis. A total of 179 breathing-zone air sampies were collected from 48 workers for arsine analysis (table 1). Arsine concentrations ranged from less than the limit of detection to 49 ;/g;m:3. The highest mean exposures were found for the battery formation job categories: process attendants (20.6 ;/g'm:{), power spin operators (14.5 ;rg,,m3), and conveyor formativn handlers (13.7 !rg:mJ). There were no dif- ferences for the arsine exposures between days. The evening shift had significan:!!: higher arsine exposures than either of the other two shifts (p < 0.05). A total of 177 air samples were co1lec:t-d for 48 workers for the measurement ,Jf particulate arsenic (table 1). Arsenic concentrations ranged from less than the limit of detection to 5.1 ;rg'm`J. Nine valurs (5.1 I' u) were above 2 !tg/m3, t h e recor?:mended exposure standard of the Nationd Institute for Occupational Safety and Health (23). The highest mean exposures were found for assembly line (post burn) (0.9 !rg `m"). element battery repa:r (0.87 ,rrg m:%)a, nd salvage and remelt 0.69 r/gjm'3)workers. There were no significant differences for the particulate a?* senic exposures between days or shifts. Forty-nine area air samples were cc;- c `Job category Assembly line Battery stackt Boosted stoc- , Conveyor for: Element batte Gravity checK High rate tes Immersion fill Power spin Process atter Salvage and Scrap coordi Tiegel opera: Office Total a Job categc , Each wor were avera of the two in the subs workers wt specimen. t. tion of that quent anal! Duplicate At the time of the collection of the lected for the measurement of arsenic tri- , plant from urine samples. each worker was asked oxide vapor (table 2). The highest mean arately to t whether he or she had eaten any salt concentrations were found for the element ment was water fish, shellfish, or crabs during the battery repair (0.36 !rg.'mJ) and post bu!-!l these dup preceding week. This procedure was de- (0.18 !rg m:j) areas. coefficient I .signed to assess the major possible dietary The six drinking water samples collected The wask source of arsenic. Also, by means of a in the plant contained no detectable a:- bottles we: supplementary questionnaire, the workers senic. arsenic ana were queried concerning their typical use in any of t of tobacco and consumption of red wine. Medical e x a m i n a t i o n After extraction with nitric, perchloric, "and sulfuric acids, urine samples were Thirty-nine (93 o) of 42 production work- Eight (11 Urinary ar5 (0.68 ,umol analyzed for total arsenic content by ers with potential exposure to airborne bations of ?.tomic absorption spectroscopy with an arsenic species participated in the medical (hble 3). automated hydride evolution technique. survey. Eight office workers participated arsenic con This technique does not distinguish among as a reference group. Were empll species of arsenic, but measures the total Forty-three of the participating workel's urinary excretion of the absorbed arsenic provided two 24-h urine samples, and foil[. the greates in battery of any species. The results of the analyses provided a single sample. The mea!l were corrected t o the specific gravity of urinary arsenic concentration (correcttsd Wnary ar (0.80 ,urn01 "standard" urine (SG 1.024). The lower for specific gravity) from the first day of battery fo limit of detection for arsenic in urine was collection was 31.5 ,,rg.l (0.42 ymol 1): and 1 !rg/l (0.013 !lmol/'l). on the second day 24.9 !rg!l (0.33 ;(mol 1). U n a r y ars &wiCework 172 Table 1. Personal (breathing zone) exposures to airborne particulate arsenic and arsine by job category - Lead-acid battery plant, November 1980. ntratioG if dete, an expo, - J forma, rtendant )peraton ormation 2 no difbetween iificantiy e r of the collected -merit of enic conthe limit $e values e recomNational ety and xposures 3st burn) repair melt 0.69 ) signifiAlate ar- shifts. vere colsenic tri2st mean . element lost burn collected :able ar- on workairborne e medica1 :.ticipated , , workers and four ?e mean corrected i t day of ol i), and ; ,/mol/l). I , Number of workers Particulate arsenic (~g/m3) Number of Mean SD samples Assembly line (post burn) gattery stacker a BosSted stock a Conveyor formation handler a Element battery repair Gravity check acid leveler Hlgn rate tester immersion filler power spin operator a process attendant a Salvage and remelt operator Sc-ap coordinator Tlegel operator Office TO.RI 4 2 2 6 5 4 2 2 2 3 3 3 2 8 48 16 8 8 23 19 12 8 8 6 12 12 11 6 28 177 3 Job category in the battery formation area. 0.93 0.08 0.08 0.09 0.87 0.08 0.08 0.66 0.08 0.11 0.69 0.09 0.32 0.08 1.38 0.0 0.0 0.02 1.53 0.0 0.01 1.64 0.01 0.08 1.15 0.04 0.43 0.00 Arsine (/cg/m3) Number of Mean samples SD 16 1.92 7.09 a 8.12 3.98 8 4.42 1.67 24 13.74 10.89 20 10.82 8.64 12 2.78 1.95 a 11.63 3.94 a 2.00 1.20 7 14.48 7.15 12 20.57 8.56 12 0.15 0.19 11 0.95 0.52 6 0.51 0.34 27 0.06 0.11 179 Each worker's results from the 2d iyvere averaged, and the arithmetic mean of the two corrected values was employed ;n the subsequent calculations. For those u ~ r k e r swho had provided only a single jprcimen, the corrected arsenic concentratiGn of that sample was used in the subsequent analyses. Duplicate aliquots were prepared at the plant from 12 urine samples and sent separ :3tely to the laboratory. Excellent agreemcint was seen for the blind analysis of i h s e duplicate specimens [correlation coefficient (r) = 0.991. The washings of four sample collection bu;tles were sent to the laboratory for ar5enic analysis. No arsenic was detected !r, any of these samples. Eight (11.0 ",u) workers had corrected uxnary arsenic concentrations of 50 !(g 1 (0.6'8 !tmoljl) or above; none had concentriitions of 100 jrg!l (1.34 !tmoll'l) or higher (tr,ble 3). AI1 the workers with urinary ar-enic concentrations of 50 !ig/l or above w*re employed in production areas, and thr greatest number (six) were employed in battery formation. The highest mean ur:nary arsenic concentration [44.6 //g 1 (0.60 !trnol/l)] was also found among the b t t e r y formation workers. The mean urinary arsenic concentration of the eight oiiice workers was 14.4 !/g;l (0.19 !tmoI 1). Table 2. Arsenic trioxide (As2O:r) vapor con- centrations by plant area - Lead-acid battery plant, November 1980. Area Boosted stock Element battery repair Battery formation Post burn Salvage and remelt Tiegel Total 10 3 11 7 11 7 49 0.02 - 0.36 0.06 0.11 0.07 0.18 0.14 0.07 0.12 0.06 0.07 Six workers reported that they had eaten seafood or shellfish during the week prior to this investigation. The urinary arsenic concentrations of these six work- ers ranged from 4.25 to 53.5 pgll (0.060.71 pmolil); the one value over 50 !rg/l (0.68 !tmoIil) was that of a battery formation worker. The mean urinary arsenic concentration of the six workers who had eaten seafood was 20.8 !tg!l (0.28 {tmolil), and the corresponding mean of the remaining 41 participants was 28.7 ,ug/l (0.38 ,umol/l). Five of the 22 workers who completed a supplementary history ques- 173 tionnaire reported that they occasionally drank red wine (maximum 1 glasdmonth). The mean urinary arsenic concentration of these five workers, was 22.9 pgil (0.31 ;imol'l), while that of the 17 workers who reported no red wine consumption was 23.4 !rg,l (0.31 {tmolil). Thirteen of the 22 workers who completed the supplementary questionnaire reported that they smoked tobacco. Their mean urinary arsenic concentration was 21.2 ygll (0.28 !lmol/l), while that of the nine nonsmokers was 26.7 pg/l (0.36 ymolil). The respondents to the supplementary questionnaire did not differ significantly from the nonrespondents with respect to urinary arsenic concentration. To evaluate quantitative relationships between the urinary arsenic concentrations and concomitant exposures to airborne arsenic species, we examined product moment correlations (6) between the mean (corrected) urinary arsenic concentratiun of each worker and his or her meac Table 3. Urinary arsenic concentrations, mean and distribution by job category - Lead-acid ba!- tery plant, November 1980. Job category Assembly line (post burn) Battery stacker b Boosted stock b Conveyor formation handler b Element battery repair Gravity check acid leveler High rate tester Immersion filler Power spin operator b Process attendant b Salvage and remelt operator Scrap coordinator Tiegel operator Office Total Number of samples 4 2 2 6 5 3 2 2 2 3 3 3 2 8 47 Urinary arsenic (ttg/I a) 50-99 trgll (N) Mean SD 0 16.9 3 8 1 42.0 21 9 0 13.6 9 3 2 46.3 28 2 2 38.4 i a 5 0 17.6 10 3 0 33.2 12 0 34.2 6 7 0 36.4 5 4 3 69.0 14 1 0 0.3 4 0 0 9.7 1 2 0 7.9 3 7 0 14.4 14 0 0 *breathing-z 'full-shift ticulate a r was under trioxide bt were avail, The corr urinary ar mean persc to arsine 5 , lationship (fig 2) Li the other llate arsenic a possible concentrat as compar nary arsei for the b group the at the pla Mean a * (95 o coni Or greater with urin 50 ,ug 1 (0 linear est Sures of 2 associated tions of i ( Discussio. a 1 /lg/il = 0.01335 :tmolil. b Job category in the battery formation area. - .YO 10 - -ID i 60 - v :51 n L0 -1I -I I c aa I1ss-. . e'., /- , 0 ,I 0 ,/ .s.-O,C I ,/' 0 // ,/- CO*IIOfMCf .,:n i i . ZU. i 17 I = am4 * oooei Fig 2. Correiation between arsine exposure and urinarv arsenic excretion - Lead-acid batte- ry plant, November 1980. (1 !ig, arsenic/! urine = 0.01335 ttmol ar- The data sults of pr shown ars in the m, batteries the likeli greatest d lead-arsen battery ac Inhaled body flu] bolically Trivalent a human been ass( three tyF disease, t mom cell skin canc Persons e in the cht 174 I -espon mnai 4le non., iry ar- mshipi rations rne ar- ct mo- mea& `- tration mean CId bat- --I -so 3.8 21.9 9.0 28.2 18.5 10.3 12.4 6.7 5.4 14.1 4.0 1.2 3.7 14.9 rrelation sine ex` urinary >xcretion - d batte- .overnber .' l l g ar- ? urine = ., 3.no1 ar- 2) breathing-zone exposures (mean of four fuli-shift samples) to arsine and to part,culate arsenic. No correlation analysis undertaken in the case of arsenic tr:oxide because only area air samples ,\..r.re available. The correlation of the workers' mean ,,:.nary arsenic concentrations with their mean personal (breathing-zone) exposures tO arsine showed a close quantitative rela:!onship ( N = 47; r = 0.84; p = 0.0001) (fig 2). Little correlation was found, on the other hand, with exposure to particulate arsenic (N = 47; r = 0.075; p = 0.62), a possible reflection of the much lower concentrations of particulate arsenic in air as compared to arsine. The highest urinary arsenic concentrations were found fcjr the battery formation workers, the group the most heavily exposed to arsine a; the plant. Mean arsine exposures of 15.6 ,icg!m3 (95 " , o confidence interval 13.2-19.4 {rgim3) IJT greater were found to be associated 1.v:th urinary arsenic concentrations of 50 !rg.1 (0.68 ,itmolil) and above (fig 2); b y linear extrapolation, mean arsine exposures of 31.2 ,ugim3 and above would be associated with urinary arsenic concentrai:ons of 100 {cgll (1.34 !tmol'l) and higher. posed through the consumption of contaminated drinking water (44) or through the use of arsenical medications (28). The prevalence of arsenic-induced skin cancer appears to be related to total arsenic dose (29, 44). Exposure to trivalent arsenic has also been associated with angiosarcoma of the liver. In such cases, exposure has been through the drinking of arsenic-contaminated wine (41), or through the use of Fowler's solution (9). Trivalent arsenic has, in addition, been found to cause cancer of the lungs and bronchi. Excess mortality from lung cancer has been observed in several studies of smelter workers (17, 19, 34, 37, 39), as well as in studies of pesticide manufacturers and formulators (12, 20, 30). vineyard sprayers (41), and underground gold miners (29). In general, the frequency of excess lung cancer for workers exposed occupationally to trivalent arsenic or to arsenic trioxide has been related directly to their cumulative lifetime arsenic exposure (26). Trivalent arsenic has, finally, been associated in two studies with increased mortality from malignant neoplasms of the lymphatic and hematopoietic tissues (2, 30). The number of cases cited in each of these reports is however small, and further evaluation of the possible relationship will be required. Discussion The data from this study confirm the re>;litsof previous investigations which have :.Town arsine to be an occupational hazard : the manufacture of lead-acid storage L:teries (16, 24). In battery production, :.-.e likelihood of arsine exposure is the 2 reatest during electrical formation, when I.>ad-arsenic alloy comes into contact with ixttery acid. Inhaled arsine is rapidly dissolved in h i d y fluids (35) and is degraded metabolically to yield trivalent arsenic (10). Trivalent arsenic is well established as 5 human carcinogen (18, 26, 33). It has bcen associated with the occurrence of three types of skin cancer - Bowen's dxease. basal cell carcinoma, and ;quar u u s cell carcinoma (28). Arsenic-induced s h n cancers have been observed among persons exposed occupationally to arsenic in the chemical (32) and wine-making (41) !ndustries. as well as among persons ex- Inhaled arsenic is, for the most part. excreted via the urine j18), and the urinary arsenic concentration appears to be the most accurate indicator of current or recent (1-3 d) absorption of inorganic arsenic (11). Urinary arsenic concentration may provide an especially accurate reflection of recent arsine absorption, given the high solubility and rapid metabolism of inhaled arsine. Although the range of values considered "normal" in previous studies of urinary arsenic concentrations has varied, due primarily to differences in laboratory methods, over 95 II of the urinary arsenic concentrations of populations without occupational or other specifically identified exposures to arsenic has been found to be below 50 !ig.'l (0.68 pmolil) (3, 11, 21, 22, 40, 47). Three studies (32. 38, 42) have reported mean urinary arsenic concentrations of 80, 85. and 130 !cg:l (1.07, 1.13, and 1.74 ,i/molil), respectively, for allegedly nonexposed groups; however, in each of the studies, persons in the "control" groups either 175 worked in proximity to arsenic-contaminated areas or had had previous occupational exposure to arsenic. The data from this investigation indicate that the current OSHA standard for occupational exposure to arsine - 200 ;ig of arsine./ms of air (46) - a standard which is intended principally to prevent the acute toxic effects of arsine inhalation (I), does not prevent chronic increased absorption of trivalent arsenic from the inhalation of arsine. The data indicate that a mean arsine exposure of 15.6 pg!m3, less than one-tenth the current legal standard in the United States, is associated with the excretion of 50 ;rg of total arsenic.:l of urine (0.68 rtmol,'l), and, by linear extrapolation, the 'data indicate that a mean arsine exposure of 31.2 /ig,m3 would be associated with the excretion of 100 /lg of arsenic11 of urine (1.34 prnoU1). To prevent potential chronic toxicity among workers exposed to arsine, consideration should be given to a downward revision of the OSHA arsine exposure standard. The current OSHA standard for exposure to other species of airborne arsenic is 10 ,ugim3 (46), and the National Institute for Occupational Safety and Health recommends 2 !i/m3 as the standard for occupational exposure to all species of inorganic arsenic, including arsine (23). It would seem reasonable that the x s i c r exposure standard be made compatible with those for other species of arsenic. Acknowledgment We should like to thank Dr G Pershagen, National (Swedish) Institute of Environmental Medicine and Department of Environmental Hygiene, Karolinska Institute, Stockholm, Sweden, for his valuable advice concerning this manuscript. References 1. American Conference of Governmental Industrial Hygienists. Documentation of the threshold limit values for substances in workroom air. Cincinnati, OH 1971, pp 16-17. 7. Axelson 0. Dhalgren E, Jansson CD, Rehnlund SO. Arsenic exposure and mortality: A case-referent study from a Swedish copper smelter. Br j ind med 35 (1978) 8-15. 3. Baker EL Jr, Hayes CG, Landrigan PJ, Handke JL. Leger RT, Housworth WF. Harrington JIvI. A nationwide survey of heavy metal absorption in children 1ivir.p near primary copper, lead, and z : : ~ smelters. Am j epidemiol 106 (1977) 261273. 4. Bulmer FMR. Rothwell HE, Polack SS. Stewart DW. Chronic arsine poisoning among workers employed in the cyan:de extraction of gold: A report of fourtern cases. J ind hyg toxicol 22 (1940) 111-124. 5. Carlin LM. Colovos G, Garland D, Jam.n F2'0. Mabui Lung posed ron hc 21. Milhat exposL Envirc- 22. Morse Landr. tiple L. a sme 23. Natior ,MI, Klenck M, Long T, Nealy CL. .4naly'- ical methods evaluation and validatii ? and F1 stand:) Rockwell International Corporation. SLjtional Institute for Occupational Safe::i , organi (NIOS and Health, Cincinnati. OH 1981. ( F i z J 24. Nation report to NIOSH Contract 210-79-00601 and t. 6. Colton T. Statistics in medicine. Lit:..,. storap Brown and Company. Boston. M-4 1974. men t 7. Costello RJ. Eller PM. 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