Document gaXpnLB2az3Za0d0yyKkJk5K9

tNHKO'MIMM tost AKt H 14, 68 - 72 (1977) Chromosomal Damage in Men Occupationally Exposed to Vinyl Chloride Monomer and Other Chemicals Ci.akk W, Hr u ii, Jr.. ,\\:> ( lit k'i i K, D( \i<) \ i L an iir ,nut liirth /></<'< f' Pmsion. Hnuiiu ot l./nih ( inh< !,>r |)hm\e I'ublu flcullh brn/ii. f S. Ihyu/l/'li el Ifentlh. I ih/i <jh"0. witI Wellwc. ItllHI Cliflti/l KtnlJ. X.li.. `Kthiniii. i/toiyni JOJ.li Jdll\ G \Mill.) Oiiupiitninul Health S/ut/itw (iniuf). lJniiiiMi\ nf \nr/Ji (\irolma w Chapel Hill. Chape! Hill. North Carolina 275N A Ml Richard J. Waxyvhi.kr National Institute for Occupational Safety ami Health. Center for Hi\ea\e ( wtirol. Cincinnati. Ohio JSJ2h Received July 14. 1976 INTRODUCTION Data tram various sources suggest that the biologic effects of vinyl chloride monomer (VCM) include mutagenicity as well as oncogenicity. Pertinent studies include observations concerning the mutagenic effects of' VC'M in bacterial test systems (Ranmig cf al.. 1974: Rartsch et til.. 1975), mutagenicity of VC'M metabolites in mammalian cells (Huberman ct al.. 1975). and cytogenetic studies of polyvinyl chloride (PVO) polymerization workers (Ducatman <7 til,, 1975: Funes-Cravioto. ct al.. 1975: Kilian ct at.. 1975: Purchase et til.. 1975). Also relevant may be observations suggesting increased fetal loss in families of PVO workers (Infante ct al.. 1976). Among the several cytogenelic studies reported, three have suggested increased chromosomal breakage among polymerization workers {Ducatman et at.. 1975: Funes-Cravioto ct al., 1975: Purchase d al.. 1975). and one has not I Kilian cl al., 1975). This report concerns cytogenetic analyses conducted on workers employed at a rubber and plastics plant, some exposed to VCM and others not. MATERIALS AND METHODS The work described here was part of a cross-sectional study designed to provide muitiphasic medical screening data on the health status of men employed at a large rubber and plastics plant The overall study was conducted jointly by the Center for Disease Control <CDC) (National Institute for Occupational Safety and Health and Bureau of Epidemiology) and the Occupalional Health Studies Group of the University of North Carolina in cooperation with the Firestone Corporation and the United Rubber Workers. Results of the entire study, together with a detailed description of the study's design and methodology, will be published separately. Cupvnght < by AtMifemiir Inc Mi rights til rtprodiKHOfl >' any fuim fpsci veJ 68 ISSN IKII t I Cytogenetic chromosomal bre mtrn; specimens > 1^75 (2 on both socl> employed i pVC polymeii/.n 4 in PV< r^>" fnaniilactuit on. history cWv.aK ss records. Initially. the m exposed to V( ^ analyses showed was selected (Ap directly to any I pared in the s.i" workers at the ; between April I VCM and induworker slides H industry-conin') from the first i\ > Jures I Moorhen*1 phyiohemagglun za r~ os Frequencies > 32 Levels of bicaka ^ were significant! the P 0-01 levv At the same lime groups themseK months worked not vary sigmfu. An effort was hence extent ot was seen lot ind bers and bceausNo gradient wh* ment or of en\pl` too small to pet Chromatid gt Similar tvpes o' groups. When review /fw-ce. ^Exposed ,ern(cals f |,ir i\f ,itnl W. If,in- ,f Ow/v) H/t). ( onlrol is of vinyl chloride v Pertinent studies M in bacterial test ugcmcitv of VCM cytogenetic studies itman <t ol.. 1^76: ,/ nl.. I97S). Also m lamilics of PVC ic studies reported. ,>ng polymerization < Purchase a til.. 'iicerns cytogenetic l.istics plant, some designed to provide i mplnv ed ul a larce :irl> hv the Center l Safety and Health unties < iroup ol the .- Coiporaiion and diet v, ith a detailed Mishevl separately. < 11Rt>MOSt)MKS AM) VINW. UII.OKIDK 69 Cytogenetic analyses, primarily designed to measure frequencies of chromosomal breakage, were performed on peripheral blood lymphocytes from 35 men: specimens were obtained from IX men in October 1974 and 19 in January 1975 <2 on both (illusions). Subjects were restricted to men primarily or exclu sively employed for JO v ear-, or longet. in 3 different employment categories: 14 in PVC poly me i i/at ion t presumed high exposure to VCM. intermittent or sustained). 4 in PVC processing (presumed low exposure to VCM). and 17 in rubber tire manufacture (industry eonliols: presumed negligible exposure to VCM). Work history details weie obtained by interview and confirmed by review of company records, initially, the study was designed to compare breakage frequencies in workers exposed to VCM with frequencies in other workers. However, when initial analyses showed no significant differences among worker groups, a control group was selected (April 1975) consisting of four male employees at CDC not exposed directly to any laboratory chemicals. Material for cytogenetic analysis was pre pared in the same manner with the same reagents as the earlier material from workers at the plant. To assess comparability in microscopic reading of slides between April 1975 and the earlier dates, previously read slides from the high VCM and industry control groups were blindly interspersed among the CDC worker slides, Breakage frequency recorded on the second reading of high VCM/ industry control slides (6.0^ of 150 scored metaphases) did not differ significantly from the first reading. Cytogenetic material was processed using standard proce dures (Moorhead <7 <//.. I960). Cells were cultured for 72 hours in the presence of phytohemagghitinin. Ciicmsa staining was used without handing. RESULTS Frequencies of chromosomal breakage in each group are shown in Table 1, Levels of breakage in all three industry groups, whether exposed to VCM or not. were significantly increased over the CDC control level, the high VCM group at the P <0.01 level, the low VCM and industry control groups at the P <0.05 level. At the same time, no significant differences were noted between the three industry groups themselves. Groups were comparable in terms of age and number of months worked. Breakage frequencies for individual subjects within groups did not vary significantly one from another. An effort was made to relate levels of breakage to duration of employment and hence extent of potential toxic exposure (Table 2). While a significant gradient *as seen for industry controls, interpretation is uncertain because of small numhns and because the mean age of subjects increased with employment duration. Sm' gradient was seen for the high VCM group, whether in terms of total employ ment or of employment in contact with VCM. The low VCM exposure group was small to permil analysis by exposure duration. Chromatid gaps comprised the majority (S6'7) of aberrations seen (Table 3). s,miUr types of aberrations were seen with similar frequencies among all four rruups. DISCUSSION 'Mien reviewed in terms of comparisons between worker and nonworker ISsNimi o*l l 4 1Uirflt j 70 HI- A 1 H ) l Al 1 AIM 1 1 I i \ m ' Cl C'H KM Mi 1ISOM \l Hkl \ k M , 1 l\S ) \ I'l >S( K 1 (imiii' Melaphnscs Nurnhei Axct.igc -...... - Avcrngo Number Number Percent t of ;igc of months worked NumlH-'r with with I'.xpoMirc suhjccls (range' Intngci scored brenknge breakage'1 High VCM 1 ow VCM Industry controls CIXcontrols 14 44.4 (44-65) 4 52.5 (46 58) 17 48.s (51 -581 4 44 5 <57 241.1 1215 - *46) 515. K (261 541) 505.8 (114-557) -- 1 105 180 1506 5K6 74 14 77 21 6.7 7.8 59 5.6 " levels of statist kill significance: High VCM vs CDC control, - 7.09, P - 0.01; low VCM vs CIX' control. - 4 64. /' - 0.05; industry control vs (.`IX' control. y - ' 45. /' = 0 05: high VCM vs low VCM. v" - It- IK. /' = 0.05: high VC'M vs industry control. *' - OKI. P - '0.05. TAIH.I- 2 l.nn.s. or CiiKmniMiMAi Bmiakai.i in Ri i v rioN i o Km 'IIM III D< U\l ION Metaphascs Exposure High VCM (total employment) High VCM (VCM employment) Industry controls Months worked 100- 199 200 - 299 XN> 399 100-199 200 - 299 300- 399 100 199 200-299 300 - 399 Number of Mibteets Average Average number age of months worked <1 _ K 47.4 6 52.2 _ 264.6 326.5 X^ (1 dfi = 0.16, P >0.05 Number scored _ 700 405 Number with breaks , 49 25 2 60.0 9 47.7 3 47.7 179.0 252.3 318.3 100 7 755 53 250 14 X* (2df> - 0.58. P>0.05 2 31.0 2 44.5 13 51.8 132.5 265.5 338.6 100 76 1130 0 1 76 X` 12 <//) - 9.91 . P -- 0.01 Percent with breaks _ 7.0 6.2 7.0 7.0 5.6 0 1.3 6.7 33 rCO 20 -Ca s | i groups, the present observations are not inconsistent with prior studies suggesting that industrial exposure to VCM is associated with an approximately twofold increase in levels of chromosome breakage as measured in culture of peripheral blood lymphocytes. In contrast with at least one prior report (Huberman et at., 1975). however, breakage consisted mostly of simple chromatid gaps rather than more complex forms. ; : ' [ f i X f 3" 3 u T -- --- -- L-J -s. I -J o s e >v o O OB -J --J c O C -- & w oe 3e ~ 'J> -J SO -.J -I -- C? S C -C ' ^ i 9- -j o c p o vC * ~-i ij l - -i -> r- CD >s HO I HOI II) 1ANIA O.W S N\OSlH\()jr i UIH|) .U-'ljllM `Jra I'tji ' pi /' IM'UI IXjll| | | | [iM.'iijili.iaU |i' o 111!;i vm \|.i jv:uu\ n u> .4 1>1 . \ 1 l '>. 0 (I I*" 4 S 11 U'., Hi S'- s. ill ; ! r-i >: '"i' 0 ; hf >*> \^iMlq (Jliw -.'V'-'H p.iu> Him J-XJUl" ID r~ CO M >1 I V H l(J <H S<l I) ./ `IH II W.)A 'IS|M si) 0 tCw i W.).\ w*| Hill ./ >. 4 A' ft's LL *'L i'4 fl n mv> JW-'I0,| Upss j>4Uir>s s.isiiqdf l-'i\ .1 I' IK 11 > 72 ov iiiifMi. ; J Cl. K1 '* S The fuel that overall breakage levels were similar in workers exposed heavily, lightly. 01 negligibly to VCM may implv. in this part ieuLir work setting at least, the presence ut' agents other than VCM capable of inducing chromosome breaks. Because of the w ide range of chemicals to which rubber workers at this plant were exposed (primarily solvents of various kinds), it was impossible to relate any particular agents to the abnormal effects observed No cleur-em pattern was seen to relate degree of breakage to duration of exposure. Lead and SUMMARY Measurements of chromosomal breakage were made in peripheral blood lym phocytes from workers exposed heavily, lightly, or negligibly to VCM at a large rubber-plastics plant. Breakage levels in all three groups were significantly in creased over levels in nonindustrial controls. BreaLrge consisted mostly of simple chromatid gaps. The results suggest that other agents, in addition to VCM. may cause cytogenetic damage in workers employed in the rubber/plastics industry. ACKNOWLEDGMENTS We wish 10 thank Mrs. Debra Jackson for her technical nssisiance and Mr. Jure Honsworth for statistical advice. REFERENCES Uartsch. H.. MuUivcitte. C . and Mmcs;ih. K. Human, at and mouse Iner-mcdmied mutagenicity of vinyl chloride in .V A {>)iiitnitoii si rains, hn. J t atu <1 15, 429 417 Ducat man. A., Hirschhorn. k.. and SelikolT. I. J 11975). Vinyl chloride exposure and tin mail chromo some aberrations, \tutnt. 51, 161 I6X. Fiines-t'raviolo, I1.. Lambert, H.. l-indsten. J..ctl (1975). i.cller to editor, I.,,iuft I, 459. Hubei mail. F... Harlech. H.. amt Sachs. 1, .0975). Mutation induction in Chinese hamster V7' t elk by two vinyl chloride metabolites, chlorocthylcnc oxide and 2-chloioacetalUehydc. hit J. (<in< 16. 679 644. Infante. P. F . Wagoner . J. K.. McMicbacl. A. J.. ft ol. i 1976). Genetic risks of vinyl chloride l.mu < i 1. 7.U-735 Kilian. 11. I.. Pivciano. 1). J.. and Jacobson. t\ H. tl97f>). Induslti.il monitoring: A cytogenetic approach. Ann. .V. ). An/d. Sri. 269. 4 II. Moorhead. P S.. Nowell, I*. IMcllnian, W. J.,<f nl. (I960). Chromosome preparation of leukocytes cultured from human peripheral blood. (VI/ Ht<>! 20, hit 616 Purchase. L F. H.. Richardson. <1. K.. and Anderson. [>. 11975), tetter to editor, l.mu ft 2. 4 It) 411. Rannug U.. Johansson A.. RamcL (' . and Waehtmeisier. C. A <1974) The mutagenicity of vinyl chloride after metabolic activation Amhio 5, 194 - 197. ,,ui> tin' Di r Knvtrvtnnt'n.> hmiud informal i evte 6-aminolcvu pregnant women activity and cr\u mean level ol W data vd-o show i activity than no and fetal erythi" inhibit erythi os r~ The adverse ol 03 yew* they have ^ descriptions to si the toxic elTeets years, this arca ol dissemination of The earliest mu inhibition of (he involved in the hi lead that it is par lead are mettsura of this enzyme h general populah. traffic policemci industrialized cn Nikkanen. WOi been found to ci One group of r toxic effects of 1 Agency. Agency has sug woman and (etuthan the general Unlhei ml ormau l ,,p, ,,,hl ''' ' " V' "