Document 9165gKgKmyymEa1OonEvpN6D

rOTICE: This material he protected by oopyr - British Journal of Industrial Medicine 1982;39:361-369 Metabolic and health consequences of occupational exposure to polychlorinated biphenyls A B SMITH,* JOANNE SCHLOEMER,' L K LOWRY,' A W SMALLWOOD,' R N LIGO," S TANAKA,* W STRINGER,' M JONES,'t R HERVIN,' AND CJGLUECK1* . From the United States Department ofHealth arid Human Services, Public Health Service, Center for Disease Control, National Institute for Occupational Safely and Health, Division ofSurveillance, Hazard Evaluations and Field Studies,1 Robert A Taft Laboratories, and Lipid Research Centre,2 University ofCincinnati Medical Centre, Cincinnati, Ohio, USA abstract In surveys of three groups of workers occupationally exposed to polychlorinated biphenyls (PCBs) serum PCB concentrations were quantitated as lower chlorinated biphenyls (L-PCBs) and higher chlorinated biphenyls (H-PCBs). Serum L-PCB and H-PCB concentrations were many times greater among workers employed in power capacitor manufacturing than among the general population, even comparing employees never assigned to work in PCBexposed areas. Statistically significant positive correlations of symptoms suggestive of mucous membrane and skin irritation, of systemic malaise, and altered peripheral sensation were noted with increasing concentrations of serum PCB. No clinical abnormalities attributable to exposure .to PCB were observed. Serum PCB concentrations were positively and significantly correlated wi Jutamic-oxa'.acetic transaminase (SGOT), serum gamma-glutamyl transpeptidase (GGTP), ana plasma triglyceride, and inversely correlated with plasma high density lipoproteincholesterol. These correlations were present across all study sites. These findings are indicative of PCBs' physiological effect on the liver, whose long-range health significance is unknown. Nevertheless, the consistent positive association of serum PCB w*th plasma triglyceride and negative association with plasma HDL-cholesterol may have long-term cardiovascular consequ ences. Polychlorinated biphenyls (PCBs), a class of chlori animal food sources,11 many countries placed nated aromatic hydrocarbon compounds, have increasingly stringent restrictions on their use. In the become widely dispersed in the environment. United States occupational exposure to PCBs is now Manufactured in the United States from 1929 to limited almost exclusively to servicing and repair of 1977 by the Monsanto Industrial Chemicals Com PCB-containing transformers arid mining machin pany and marketed under the tradename Aroclor, ery; operation and servicing of hydraulic and heat the growth in their annual sales to a peak of transfer systems that may still be contaminated with 85 054 000 pounds in 1970' is evidence of their ver detectable levels of PCBs despite efforts to drain satility and of a past general lack of concern for their and replace them with non-PCB substitutes; and potential toxicity. After 7 series of mishaps that recycling waste oils, sludges, and products coated resulted in contamination by PCBs of human and with substances that contain PCBs. Inadvertent -Present address: Medical Division. E I duPont de Nemours and Co, Inc, Wilmington, Delaware. tPrescnl address: Kaiser Aluminum and Chemical Company. Ravenswood, West Virginia. exposure may occur as well, stemming from leaks of closed-system devices such as capacitors and trans formers that contain PCBs. In 1975 the National Institute for Occupational tDr Glucck's support (or this work came from NHLBI Contract No Safety and Health (NIOSH) initiated a study of the 1-HV2-2914L (Lipid Research Clinics) and General Clinical effects of occupational exposure to PCBs. This Research Cenue Grant RR00068-18. ' report describes cross-sectional surveys of three . Received 14 September 1981 Ar--oted 9 December 1981 groups of workers occupationally exposed to PCBs. ' The places of employment were an electrical equip- 361 mi TOWOLDMONOQ59892 362 Smith, Schtoemer, Lowry, Smallwood, Ligo, Tanaka, Stringer, Jones, Hervin, and Clueck ment manufacturing plant, with exposure to 42% haul of transformers at a maintenance facility. Data chlorinated biphenyl in the manufacture of electrical were obtained from 46 employees of the private util power capacitors; and a public and private utility ity company--15 who' worked in transformer company, with exposure to 54% chlorinated maintenance, 10 in transformer overhaul, and 21 in biphenyl in the maintenance and repair of distribu other jobs without occupational exposure to PCBs. tion transformers. The electrical equipment manu facturing plant was chosen for study because a con INDUSTRIAL HYGIENE EVALUATIONS current epidemiological study of community resi Reports describing industrial hygiene evaluations at dents41 provided background data on serum PCB each fadlity are available from ABS on request. concentrations within the general community. The Ambient levels of airborne PCB and levels of skin two utility companies were included in the survey contamination with PCB were measured during sur because the type of work performed there was veys of industrial hygiene conducted at times thought to represent occupational exposures to roughly concurrent with the medical surveys. Per PCBs that were likely to continue in the electrical sonal air samples were collected on florosil, a mag industry.6 ' nesium silicate absorbent, by using a Sipin SP1 pump operating at a flow rate of about 200 cc/min Materials and methods for two to seven hours. The PCBs were desorbed from the florosil with benzene and analysed by using STUDY SITES AND POPULATIONS a gas chromatograph with an electron capture detec The electrical equipment manufacturing plant began tor. The limit of detection was 0 01 /ig per tube. operations in 1958. The production of large power Skin wipes were collected on Whatman smear tabs capacitors was the only operation using PCBs. From No 50 by wiping the forehead, nose, and cheek area 1959 to 1971 Arodor 1242 was used; after 1971, of selected workers. The wipe samples were ana Arodor 1016 was used. Aroclor 1242 and 1016 are lysed by the same procedure to. determine the both 41-42% chlorinated biphenyls, but Aroclor amount of removable surface contamination with 1016 has fewer biphenyl homologues with five or PCBs. greater chlorine, atoms per biphenyl nucleus than Aroclor 1242.' At the time of the survey (April CLINICAL METHODS 1977), the impregnation fluid was being switched The medical surveys were undertaken to determine from PCBs to an isopropyl biphenyl. The areas of the relation between selected dinical and biochemi presumed greatest exposure to PCB were the cal findings, and plasma PCB concentration as an capadtor-processing area (designated- department indicator of occupational exposure to PCB. A ques "F-30") and maintenance (designated department tionnaire was administered to each participant by a "G-44") which required work throughout the whole trained interviewer to obtain demographic data, and plant. Data were obtained from 228 active white work hygiene, alcohol and tobacco consumption, employees of the electrical equipment manufactur family and medical'histories (a copy is available ing plant: 167 hourly employees (140 men, 24 from ABS on request). Present and previous occu women) and 61 salaried employees (59 men, 2 pational histories were obtained from plant em women). ployment records. A brief physical examination was At the public utility company the operation with performed by one of three physidans. N .ither the potential exposure to PCBs entailed maintenance interviewer nor physidans were blinded with respect ' work on transformers filled with " Askarel." Askarel to the jobs held by the partidpants. contains PCBs (Arodor 1254 or 1260) either alone The following determinations were performed or in combination with tri- or tetrachlorobenzenes, using standard methods on blood drawn after a or both. Work was done on the protector and prim 12-hour fast: haematology (haemoglobin, ary switches (only the primary switch contained haematocrit, leucocyte, and differential count), Askarel) of about 125 transformers throughout the SMA 12/60 (serum calcium, inorganic phosphorous, year. Data were obtained from 47 employees of the glucose, urea nitrogen, uric add, cholesterol, total public utility company--14 who worked in trans protein, albumin, total bilirubin, alkaline phospha former maintenance and 33 in other jobs without tase, lactic dehydrogenase, and glutamic-oxalacetic occupational exposure to PCBs. transaminase (SGOT)), serum glutamic-pyruvic At the private utility company the operations with transaminase (SGPT), serum gamma-glutamyl potential exposure to PCBs were maintenance transpeptidase (GGTP), serum creatinine, serum operations--that is, draining and filling operations direct bilirubin, serum. T-4, serum protein elec on transformers that contained Askarel and yearly trophoresis, and blood lead. Urinary creatinine and inspections of the transformers--and limited over quantitative coproporphyrin, uroporphyrin, and 0755260 TOWOLDMONOQ59893 Metabolic and health consequences of occupational exposure to polychlorinated biphenyls 363 porphobilinogen were measured on spot urine specimens. Urinary glucose and protein determina tions were performed at the study site by dipstick method. Plasma total cholesterol, triglycerides (TG), and high density lipoprotein cholesterol (HDL-C) determinations were performed. by the Lipid Research Centre, University of Cincinnati, follow ing standardised Lipid Research Centre methods,'' slightly modified'for HDL-cholesterol determina tions.* Low density lipoprotein cholesterol (LDL-C) levels were calculated9 in all subjects except three with triglyceride levels greater than 400 mg/dl. The clinical evaluations at the public and private utilities were- identical with those described above, except that, in addition, urinary 17-ketosteroid and 17-hydroxysteroid concentrations were measured and standardised for urinary creatinine excretion on spot urines. Serum PCB determinations were performed by Environmental Science and Engineering, Inc, in Gainesville, Florida, using a slightly modified ver sion of an electron capture gas chromatographic procedure developed for the Office of Toxic Sub stances, United States Environmental Protection Agency.,#n PCB components were quantitated as lower chlorinated biphenyls (L-PCBs) and higher c inated biphenyls (H-PCBs) by comparing retention times on the gas chromatogram with those of standard samples of Aroclor 1242 and Aroclor 1254. Peaks eluting before DDE (injected in the column in a pesticide mixture control) were included in the serum L-PCB determination, and those after DDE in the serum H-PCB determination. The L-PCBs so quantitated were predominantly biphenyl molecules with four or fewer chlorine atoms per molecule, and the H-PCBs were pre dominantly biphenyl molecules with five or more chlorine atoms per molecule.11 Major peaks that appeared in both Aroclor 1242 and 1254 standards with equivalent retention times were quantitated only once, as either serum L-PCB or serum H-PCB. Because of the similarity in composition of Aroclor 1016 and Aroclor 1242, no specific quantitation was attempted'for Aroclor 1016, and instead the serum L-PCB quantitation was taken to be representative of the distribution of PCB isomers found in both these products. Because of the low concentrations of PCB, mass spectral confirmation of individual peak identity was not attempted. Quality control proce dures included the analysis of two in-vitro spiked pool specimens and of one blind split duplicate in each analytical run. STATISTICAL METHODS Inspection of histograms and normal probability plots of the various blood tests showed that logarithmic transformation (base 10) was required to "normalise" the following data: serum L-PCB and H-PCB concentrations, SGOT, SGPT, GGTP, AK, total and direct bilirubin, glucose, BUN, creatinine, T-4, TG, HDL-C, and LDL-C. Para metric statistical analyses were performed with the log-transformed data, using standard packaged statistical programs.1*'15 Deficits in tabulations from specified total numbers of participants are attribu table to missing values for data, which required elimination of the individuals with the missing values from the particular analysis.' . Results . ENVIRONMENTAL PCB LEVELS Electrical equipment manufacturing plant--The time-weighted average (TWA) personal air sample concentrations of PCBs, all obtained for workers in F-30, G-44, or an area ("miscellaneous assembly") adjacent to the impregnation ovens (located in F-30), ranged from non-detectable to 264 #ig/m\ with a median of 81 pg/m*. The current OSHA standard and ACGIH threshold limit value for 42% chlorinated biphenyls are both 1000 pg/m1. Skin smear wipes of selected workers, all from F-30 or the area adjacent to F-30, ranged from 10 Mg/100 cm* to 668 Mg/100 cm1 of PCB accumulated over the course of a shift. These findings indicated workrelated skin contamination by PCBs that would not be quantified under present sampling methods, which are limited to air sampling for PCBs. Public utility company--Two industrial hygiene surveys were conducted, one in November 1976 and the other in August 1977. During the November survey, all personal air samples for PCBs (analysed as Aroclor 1254) were under the limit of detection, --that is, under 1 Mg/tube, corresponding to a con centration of under 19 pg/m*. During the August 1977 survey, personal air samples for PCBs (analysed as Aroclor 1260) ranged from 37 to 215 Mg/m*. The current OSHA standard and ACGIH threshold limit value for 54% chlorinated biphenyl are both 500 pg/m*. Private utility company--Samples obtained during yearly inspection of transformers in underground vaults showed personal air exposures varying from 0-4 to 8-8 Mg/m5. Wipe samples from the hands and face of two employees varied from 5 pg/100 cm1 to 487 Mg/100 cm1. A wipe of the table top containing test equipment and the floor of the test area showed about 800 Mg/100 cm1 for PCBs, showing localised or general smearable contamination. Personal air samples obtained during overhaul of transformers varied from 3-1 to 82-3 pg/m*. Wipe samples from- 0755261 .435,* i>^aas_ 364 Smith, Schloemer, Lowry, Smallwood, Ligo, Tanaka, Stringer,. Jones, Hervin, and Glueck various tools and pieces of equipment varied from non-detectable (under 0-01 p.g/100 cm1) to 38 pzj 100 cm1. SERUM L-PCB AND H-PCB LEVELS Serum geometric mean L-PCB and H-PCB concen trations, 95% confidence intervals on the means, and range, are given for survey participants at each study site (tables 1, 2). As background data, it should be noted that the arithmetical mean L-PCB and H-PCB concentrations among residents of the community in which the electrical equipment manu facturing plant was located, without occupational or known unusual exposure to PCBs, were 11*6 ng/ml and 12-8 ng/ml, respectively. Mean serum L-PCB concentrations among work ers at the electrical equipment manufacturing plant ranged from about eight to 50 times the community background level, and mean serum H-PCB concen trations ranged from about two to four times the community background level. Mean serum L-PCB concentrations were many times greater among workers at the electrical equipment manufacturing plant compared with transformer maintenance and Table 1 Mean serum geometric mean L-PCB concentrations, 95 % confidence levels, and range Job description Electrical equipment manufacturing plant Current job in dept F-30 Current job in dept G-44 . Current job in neither F-30 nor G-44, but ever worked in F-30 ot G-44 Current job in neither F-30 nor G-44, and never Worked in F-30 or G-44 Community residents1 Public utility company PCB exposed . PCB non-exposed Private utility company PCB exposed PCB non-expoacd . So 14 12 55 140 89 14 32 25 . 22 Geometric mean L-PCB (ng/ml) and 95% confidence interval 502 306, 824 237 137,407 149 118.188 89 77, 103 11*6 (arithmetical mean) 14 15. 39 18 15, 35 * 22 17, 25 21 14. 27 . Range (ng/ml) 210-3330 34-2400 8-1500 1-370 5-52 1-59 9-48 12-52 Table 2 Mean serum geometric mean H-PCB concentrations, 95% confidence levels, and range Job description No Electrical equipment manufacturing plant Current job in dept F-30 Current job in dept G-44 Current job in neither F-30 nor G-44, but ever worked in F-30 or G-44 Current job in neither F-30 nor G-44, and never worked in F-30 or G-44 Community residents* . Public utility company PCB exposed PCB non-exposed Private utility company PCB exposed PCB non-exposed 14 12 55 140 89 14 . 32 25 22 ' Geometric mean L-PCB (ng/ml) and 95% confidence interval 44 31,62 51 24. 74 27 23, 32 22 20, 24 12-8 (arithmetical mean) 24 15, 39 7 4. 10 29 20. 43 8 5. 11 . Range . (nglml) 20-250 10-250 7-130 1-110 7-24 1-19 7-250 3-25 0755262 TOWOLDMON0059895 Metabolic and health consequences ofoccupational exposure to polychlorinated biphenyls 365 repair workers, while mean serum H-PCB concen trations among workers at the electrical equipment manufacturing plant more closely resembled con centrations among the transformer maintenance and repair workers. The relation of serum log(L-PCB) and log(H- PCB) concentrations, and personal air levels of PCBs, was examined among workers at the electri cal equipment manufacturing plant. Time-weighted average personal air level exposure measurements were available for 10 job descriptions, to which 20 participants in the survey were assigned. The corre lation of personal PCB air levels with serum log(L- PCB) concentration was significant (r = 0-66, p = 0 0013); but the correlation of personal PCB air levels with serum log(H-PCB) concentration was not (r = 0*37, p = (Ml). The lack of statistical significance of the latter correlation may well have been a function of the size of the data set available for the analysis. Data were not available to permit similar analyses for the transformer maintenance and repair workers. . The use of protective equipment (protective clothes, gloves, and respirators) increased with per sonal air level exposure. Thus, while a significant positive correlation between the use of protective er ment and serum log(L-PCB) and log(H-PCB) co..~ntrations could be shown (data not given), the primary association was likely between personal air level exposure and the use of protective equipment rather than the use of protective equipment and serum log(PCB) concentration. QUESTIONNAIRE DATA The relationships between serum PCB concentra tion and response to questions concerning symptoms and past illnesses were examined. Age and study site were potential confounding variables that had to be taken into account in the analysis, so that it might reasonably be inferred that any observed associa tions had not resulted from the effect of the con founding variables alone. The questionnaire response data were analysed by a logistic regression in which the logarithm of the odds for a positive ("Yes") response for the dichotomous variable (questionnaire response) was modelled as a linear function of independent predictor variables, such as serum log(L-PCB) and log(H-PCB) concentrations, as well as the confounders' age and study site. The following histories of symptom were significantly associated with either serum log(L-PCB) or log(HPCB) concentration, or both, in the presence of the confounders (see table below). PHYSICAL EXAMINATIONS No consistent patterns of abnormalities were noted on physical examination at any study site. None of the participants was found to have acneform lesions suggestive of chloracne. Although a correlation was noted between serum log(H-PCB) concentration and diastolic blood pressure at the electrical equip ment manufacturing plant (r = 0 1395, FUJ,, = 4-61), multiple linear regression including the addi tional confounding variables age and sex showed the apparent association of diastolic blood pressure with increasing serum log(H-PCB) concentration to have been attributable to an association primarily with age (partial r = 0-2742, F, ,,, = 17-64) as well as with sex (partial r = 0-1381, F1i117 = 4-27). LABORATORY DATA--BLOOD TESTS Simple correlations between serum log(L-PCB) and log(H-PCB) concentrations and the results of clini cal biochemistry and haematological tests were computed for participants at each study site separ ately. Statistically significant correlations are sum marised in table 3. To control for confounding by age (and sex, at the electrical equipment manufac turing plant), multiple linear regression equations were computed for each statistically significant cor relation, with serum log(PCB) concentration, age, and (at the electrical equipment manufacturing plant only) sex as independent variables. Because of the collinearity of serum log(L-PCB) and log(HPCB) concentrations, separate regressions were computed, with serum log(L-PCB) and the confounders) as predictors, and serum log(H-PCB) and the confounder(s) as predictors. The squared partial correlations, "partial R1," were computed. This is a measure of the variance of the outcome variable still to be accounted for by serum log(PCB) concentration, relative to the variance already Symptom . Coughing on the job or toon after work lrriiated er burning eyes Unexplained Iota of appetite Unexplained tingling in tbe hands Rath or dermatitis pWv'(l) 3-84) - 04)5. Associated with tog(L-KB) level in presence of confounders - x'(l)* 5-05 7-66 5-70 5-16 0-04 . Associated with log(H-FCB) level in presence of confounders -- 3-87 11-29 3-40 3-51 4-51 0755263 -'-'Al 366 Smith, Schloemer, Lowry, Smallwood, Ligo, Tanaka, Stringer, Jones, Hervin, and Cltteck Table 3 Product-moment correlations between selected clinical biochemistries and haematologies and serum log(L-PCB) and log(H-PCB) concentrations, by study site Clinical biochemistry Electrical equipment manufacturing plant Log(SGOT) Log(GGTP) 1 Unc acid Cholesterol Logftriglyceride) Log(HDL-cholesierol) Log(LDL-cbolestcrol) ' Beta-globulin Haemoglobin Public utility company Log(tngiycende) Log(HDL-<holterol) Private utility company Log(SGOT) Cholesterol ' Statistically significant (p < 0*03) correlation. No of observations 220 217 220 221 221 221 218 217 221 46 46 46 46 Correlation with serum log(L'PCB) 0-1308* 01936* 0-1151 01308 01621* -00837 00575 01163 0-0617 0-0222 00528 03173* 0-2872* Correlation with serum log(H-PCB) 01894* 02651* 01955* . 02615* 03212* -01473* 01473* 01526* 01492* ' 0-4292* -04148* -0-0927 00471 accounted for by the regression on the confounders alone.16 The results are summarised in table 4. Neither serum log(L-PCB) nor log(H-PCB) con centrations were significant predictors of serum uric acid, beta-globulin, LDL-cholesterol, or haemoglo bin when confounding variables age and sex were taken into consideration. Significant partial correla tions, however, in the presence of the confounding variables, between log(SGOT), log(GGTP), choles terol, log(triglyceride), and log(HDL-cholesterol); and either serum log(L-PCB) or log(H-PCB) con centrations, were still shown at at least one site. Given the same data available at three sites, it would be reasonable to expect meaningful correlations/associations to be found at more than one site. Accordingly, homogeneity of trend was investigated across all three sites by an analysis of covariance. The results are summarised in table 5. It is apparent that log(SGOT), log(GGTP), log(iriglyceride), and log(HDL-cholesterol) were Table 4 Partial correlations between clinical biochemistries and serum log(L-PCB) and log(H-PCB) concentrations, by study site ' Clinical biochemistry Electrical equipment manufacturing plant Log(GGTP) Unc acid Cholesterol Log(triglyceride) LogtHD L-cholesterol) Log(LDL-cholcsterol) . Beta-globulin Haemoglobin Public utility company Log(SGOT) Log(GGTP) Cholesterol Logftriglyceride) LoglHDL-cholesterol) Log(LDL-cholesterol) Private utility company Log(SGOT) Log(GGTP) Cholesterol Log(triglyceride) LogfH D L-cholesterol) Log(LOL-cholesterol) * Statistically significant (p < 0-05) correlation. Correlation with strum tog(L-PCB) 01085 01618' 0-0037 0-0899 0-1234 -00449 0-0001 00086 OOOOO 01436 0-0724 -00827 0-0819 0-0242 -OOlll . 03182* 0-0859 0-3227* 0 2661 00929 0-0421 . Correlation with strum bg(H-Pt'B) 01579* 02017* OOIOI 01822* 02526* -00887 00027 00128 00028 -01753 -00777 -02020 05182* -04403* 00474 -01242 -02115 -00357 -00494 -01425 00007 0755264 . I3t?5 TOWOLDMONOQ59897 Metabolic and health consequences of occupational exposure to polychlorinated biphenyls 367 Table 5 Inter-site comparisons ofcorrelations: homogeneity oftrend ofselected clinical biochemistries with serum log(L-PCB) and log(H-PCB) plus confoiinders Clinical biochemistry LogtSGOT) Log(GGTP) Cholesterol Log(triclvceride) Log( H DL-cholesterol) Regression on serum logtL-PCB) plus confounden Homogenous trend? Significant trend? Ye* Ye* Ye* Ye* Ye* No ` Ye* Ye* Ye* No Regression on serum log(H-PCB) plus confounden Homogenous trend? Significant trend? Ye* No No No. Ye* No . No No Ye* Ye* ' significantly associated with either serum Iog(LPCB) or log(H-PCB) concentrations, or both across all three sites. The trend was homogeneous for log(SGOT) regressed on log(L-PCB), log(GGTP) regressed on log(L-PCB), log(triglyceride) regres sed on log(L-PCB), and log(HDL-cholesteroI) regressed on log(H-PCB). The trend was not homogeneous for log(triglyceride) regressed on log(H-PCB).. Biochemistries for which non homogeneity of trend was noted in the absence of significant trend were of no practical interest. LABORATORY DATA--URINE TESTS Urinary glucose, protein, porphyrin, and steroid ex<--'don were not correlated with either serum L- 3 or H-PCB concentrations. Discussion Serum log(PCB) correlated significantly with symp toms suggestive of mucous membrane and skin irri tation, of systemic malaise, and of altered peripheral sensation; and with serum log(SGOT), log(GGTP), plasma iog(triglyceride), and log(HDL-cholesterol). These correlations occur in the absence of overt clinical dysfunction identifiable on physical exami nations. The simultaneous changes in SGOT, GGTP, plasma triglyceride, and HDL-cholesterol are evidence of an effect on the liver of exposure to PCB, the biological significance of which is not clear. A positive correlation between serum GGTP and triglyceride has been described,11 as has the rise of serum GGTP in the presence of drugs known to induce liver microsomal enzymes." It has been sug gested that the positive association of GGTP and triglyceride may reflect hepatic microsomal enzyme induction, with an increase in the hepatic content of enzymes related to triglyceride synthesis." In sup port of this conjecture, PCBs are well known to induce hepatic microsomal (mixed function oxidase) enzymes both in laboratory animals20 and in man.11 Therefore, alterations in liver enzyme tests in association with increasing serum PCB concentra tion ` may not themselves be predictive of future ch :c liver disease but may reflect liver micro somal enzyme induction. It should be emphasised, however, that the consistent inverse associations of loe(H-PCB) with log(HDL-cholesterol) at all three worksites may have long-term cardiovascular significance, given the significant inverse, indepen dent associations of HDL-cholesterol with coronary artery disease.22 In general, a lack of clinically apparent illness among workers with high levels of exposure to PCB and high serum PCB concentrations seems to have been the rule.21-2' None the less, correlations of exposure to PCB or serum PCB concentrations have been reported with various clinical biochemical tests in the absence of clinically detectable disease, including positive correlations with SGOT2*" and GGTP2* (Avitto V N. 15th annual meeting of US Public Health Service Professional Association, Houston, 26-29 May 1980), negative correlation with serum'bilirubin," and positive correlations with plasma cholesterol2* and triglyceride.51011 More recently, however, findings of "dermatotoxicity" in association with increasing plasma PCB concentra tions, and of increasing serum triglyceride concen trations in association with increasing plasma PCB concentrations, have been reported.11 Two reports1114 from Italy have documented, among workers exposed to 54% chlorinated biphenyl in the manufacture of electrical capacitors, signs of "hepatotoxidty" (primarily hepatomegaly) along with rises of liver enzyme tests and four cases of chloracne (among 80 workers). No "definite associ ation" was found between chloracne and blood PCB concentration. By contrast, abnormal liver enzyme tests and blood PCB concentrations, particularly trichlorobiphenyl blood concentrations, were posi tively associated. One would expect that adverse human health, effects from exposure to PCB, if they exist, would most readily be identified in groups with the greatest exposures (excluding poisoning attributable to acci dental contamination of food). None of the pub lished occupational or epidemiological studies (including ours), however, have shown that occupa tional exposure to PCBs is associated with any adverse health outcome, to be distinguished from 0755265 368 Smith, Schloemer, Lowry, Smallwood, Ligo, Tanaka, Stringer, Jones, Hervin, and Clueck demonstrable subdinical biochemical alterations. An exception to this is the occurrence of chloracne during the early years of its manufacture and use, and possibly currently as well, depending on circum stances of its use and exposure. This inability to show convincingly an adverse effect on human health from occupational exposure to PCBs may be partially attributable to the often encountered con fusion of multiple chemical exposures in the work place or in the general environment, which either directly or in combination, influence the health of exposed individuals. It is necessary to recognise, however, that clinical and epidemiological methods generally are not available that are sufficiently sensi tive and specific to allow a high degree of confidence that, when no significant individual or group effectshave been found, an adverse health effect still has not been overlooked. None the less, it is reasonable to emphasise the following observations that may have implications for a recommended standard for occupational exposure to PCBs. (1) Occupational exposure to PCBs may result in surprising rises in serum PCB concentrations among exposed workers (as in the electrical equipment manufacturing plant). Even for periodic low-level occupational exposure to PCBs (the two utility companies), demonstrable increases in workers* serum PCB concentrations could be identified. (2) Contamination of the skin with PCBs could be documented. Such contamination might consti tute a significant source of occupational exposure to PCBs, even though such contamination is not read ily quantifiable by routine industrial sampling methods. Although air level monitoring does not reflect the sole route of occupational exposure to PCB, environmental control based on PCB air level measurements, coupled with adherence to work practices intended to limit PCB skin and environ mental contamination, would probably provide a reasonable and acceptable approach to controlling exposure and absorption of PCB. (3) Statistically significant correlations of certain symptoms, serum log(SGOT), log(GGTP), plasma log(triglyceride), and log(HOL-cholesterol) with serum log(PCB) concentrations may be shown. These correlations remain significant when compari sons are made across three study sites widely separ ated in geographical distance. Although the meaning of these changes for the long-range health outcome of workers exposed to PCBs is open to speculation, these trends suggest that occupational exposure to PCB should be minimised. Unfortunately, data collected at one point in time do not allow the estimation of the cor relation between serum PCB concentrations and PCB personal air exposures that prevailed at times before the survey, and the data in themselves do not provide evidence to suggest a specific permissible exposure limit. References . 1 Lloyd JW, Moore RM, Woolf BS, Stern HP. Polychlorinated biphenyls. JOM 1976;18:109-13. I Higuchi K. ed. PCB poisoning and pollution. New York: Academic Press, 1976. 'Spaulding JE, Wessel JR. Occurrence and sources of PCBs in food. In: Interdepartmental task force on PCBs. Polychlori nated biphenyls and the environment. Springfield, Va: US Department of Commerce, 1972. *Bergh AK, Peoples AS. Distribution of polychlorinated biphenyls in a municipal wastewater treatment plant and envi rons. Science o/die Total Environment 1977;8:197-204. ' Baker EL Jr. Landrigan PJ, Glueck CJ. et aL Metabolic consequ ences of exposure to polychlorinated biphenyls (PCB) in sew age sludge. Am J Epidemiol 1980;112:553-63. * Environmental Protection Agency. Polychlorinated biphenyls (PBCs): toxic substances control. Federal Register 1977;42:26564-77. T Lipid Research Clinics Program. Manual oflaboratory operations 1974. Washington DC: 1975. (DHEW Publication No (NIH) 75-628.) * Ishikawa TT, Brazier JB, Steiner PM, Stewart LE, Gartside PS, Glueck CJ. A study of the .heparin-manganese chloride method for determination of plasma alpha-lipoprotein choles terol concentration. Lipids 1976;11:628-33. Friedewald WT, Levy RL Fredrickson DS. Estimation of the concentrations of low-density lipoprotein cholesterol in plasma without use of the preparative ultracemrifuge. Clin Chem 1972;18:499-502. "Environmental Sciences and Engineering. Inc. Analysis of polychlorinated biphenyl (PCB) in human blood serum sam ples. Final report. Gainesville, Florida: ECEI, 1977. (Research request No 2. EPA contract 68-01-3248.) II Taylor DG, ed. NfOSH manual of analytical methods. 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