Muller, John MD, MPH; Allstadt, Karen MD, MPH; Rennix, Christopher ScD, MS; Betts, Lawrence MD, PhD; Krevonick, Patricia BS; Hammett, Mark MD, MPH
Medical surveillance examinations on workers exposed to specific toxicants in the workplace are mandated by federal regulation.1 Navy occupational medical surveillance programs, including occupational medical surveillance programs for exposures to certain metals, are conducted in accordance with the Medical Matrix, a compilation of surveillance program requirements that meet or exceed federal regulations.2 Occupational exposure to various metals has been associated with alterations in hematological parameters: arsenic and lead (Pb) have been associated with anemia, and mercury (Hg) has been associated with increased red blood cell count and decreased red cell hemoglobin.3–5 Chronic nonoccupational exposure to a form of chromium (Cr), Cr picolinate (in which Cr exists as Cr+3), has also been associated with anemia.6 True anemia results from blood loss or from decreased production or increased destruction of erythrocytes.7 Medical Matrix requirements include a complete blood cell count (CBC) in medical surveillance programs for the metals arsenic hexavalent Cr (Cr+6), Pb, and Hg.
Changes in 2006 to the Occupational Safety and Health Act hexavalent chromium standards lowered the Cr+6 action level to 2.5 micrograms per cubic meter of air, calculated as an 8-hour time-weighted average, and a directive was issued to Occupational Safety and Health Act inspectors to examine more closely worksites with detectable surface levels in eating and drinking areas.8,9 As a result of these changes, industrial hygienists at a Navy military aircraft maintenance repair facility (MRF) recommended including workers from additional shops in the Cr+6 medical surveillance program. The recommendation was made because some chrome-related operations were being moved to different locations and, based on previous sampling results, these shops were now going to meet the (now lowered) exposure criteria for medical surveillance program enrollment. Personnel at the MRF performed paint application and removal, welding, and machining operations involving products and processes containing metals. Some processes were unique to aircraft maintenance and repair. Workers were routinely examined under different programs because of potential exposure to numerous toxicants, including Cr+6, aluminum (Al), cadmium (Cd), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), mercury (Hg), silver (Ag), strontium (Sr), and zinc (Zn). Biological monitoring was only performed as part of medical surveillance programs for Cd (blood and urine), Pb (blood), and Hg (urine).
The MRF worker population was part of a coastal community in which many people participate in water-related recreation, especially fishing. In addition, the MRF encouraged workers to donate blood by offering time-off awards. Seafood was a major dietary component. Area groundwater had been found to contain arsenic, and some of the population's drinking water came from local wells.
In early 2009, the occupational and environmental medicine (OEM) physician performing routine surveillance examinations on workers recently enrolled in Cr+6 medical surveillance noticed that an unusually large number of hematocrit values were below the laboratory lower limit of normal; thus, those workers were classified as anemic. An extensive investigation was launched to determine the extent of abnormal laboratory findings among the workers and potential excessive occupational exposures to certain metals. Upon learning why they were undergoing further testing, workers became concerned about possible excessive exposure to Cr+6, to the extent that T-shirts were produced, worn by workers on Fridays, emblazoned with skull and crossbones and proclaiming “I am being poisoned by chrome VI.” Requests for environmental differential (“hazardous duty”) pay were also made. Local consultative support was requested from industrial hygiene, hematology, and pathology. In addition, the Navy and Marine Corps Public Health Center and an independent OEM physician-toxicologist were brought in for support in the investigation. This report details the salient findings of the occupational health investigation of the abnormal laboratory values and the industrial hygiene sampling.
A workplace walk-through was completed, and industrial hygienists performed surface and air sampling within the involved shops. Personal breathing zone (PBZ) air sampling was performed on workers representative of various jobs being done. Semiquantitative surface sampling was performed in 54 shop areas for 16 metals: those known to be present plus five others that are part of a panel (“Inductively Coupled Plasma Scan”) offered by the laboratory, including arsenic beryllium (Be), cobalt (Co), molybdenum (Mo), and vanadium (V). Sampled areas included floors, working surfaces, workbenches, walls, windowpanes, desks, break room tables, and the top of a printer. Testing for Ag was limited to only those areas where Ag was used (24 areas).
To evaluate laboratory-to-laboratory variability, split whole blood samples of workers not enrolled in a metal surveillance program were sent to the local naval hospital (in-house) laboratory and to a private local laboratory for CBC analysis to verify the apparent prevalence of anemia among workers. In the early stage of the investigation, a hematocrit value below the local naval hospital laboratory normal range was used as the primary determinant of the presence or absence of anemia. As the investigation proceeded and in an effort to use a directly-measured parameter, investigators decided to use hemoglobin instead of hematocrit to determine the presence or absence of anemia.
The OEM physician initially reviewed CBC values from workers enrolled in Cr+6 surveillance. She subsequently expanded the review of CBC values to workers enrolled in one or more metals surveillance programs (ie, not only Cr+6 surveillance). Each worker initially classified as anemic had at least one previous hematocrit value; the initial hematocrit was used as a baseline to evaluate for change over time. Workers with low hematocrit (initially) and low hemoglobin (later in the investigation) were recalled to the occupational medicine clinic for repeat CBC testing. Those whose repeat values remained low were contacted and offered follow-up by their personal physician or by the OEM physician. The latter evaluation consisted of a standardized in-depth occupational, social, and medical history, a complete physical examination, and extensive laboratory testing to determine the etiology of the worker's anemia. Hematocrit and hemoglobin values were entered into a Microsoft Excel10 spreadsheet, and analyzed using SPSS11 Paired Samples t Test and results plotted in histograms.
Measurement of blood or urine metals was obtained in a limited number of workers. Blood and urine Cr levels were determined in 11 of the anemic workers evaluated by the OEM physician. Knowledge of medical findings beyond routine surveillance was limited to workers with anemia who chose the OEM physician to do follow-up and those who communicated to the OEM physician the results of evaluations by their private health care providers.
Initially, 318 workers were identified as enrolled in surveillance programs for one or more metals. Eventually, this was expanded to include a total of 331 workers who had CBC results. Of 331 workers, 14 had repeat hematocrit values below 37 (ie, below what could be explained by hematocrit-calculation variations) and 43 had hemoglobin values below 14. Thus, 54 of 331 workers, or 16.3%, were anemic when using hematocrit or hemoglobin (or both) as criteria. Of those, 20 were further evaluated by the local naval hospital OEM physician. Selected demographic information on workers is summarized in Table 1.
Differences between initial and recent hematocrit values ranged from −11.3 (hematocrit decreased from 45.4 to 34.1) to 12.8 (hematocrit increased from 26.9 to 39.7). As a hematocrit of 26.9 in a new hire factory worker seemed unusual (ie, the 26.9 value may be spurious, although that individual was noted to have other hematocrit values of 21.3 and 39.7), summary statistics were calculated with and without that record (ie, for 318 and 317 workers, respectively). For 318 workers, the mean change in hematocrit was −1.1 (median of −1, standard deviation of 2.6, and a variance of 6.8). For 317 workers, the mean change in hematocrit was −1.1 (median −1.0, standard deviation of 2.5, and variance of 6.2); including the 26.9 hematocrit did not much change the analysis. Thus, for 317 (318) workers with an average of 4.7 years between initial and most recent hematocrit, there was an average decrease in hematocrit of 1.1 (significance <0.001). Superimposed curves derived from histograms illustrate the decline in hematocrit values in Figure 1.
Eventually, 115 workers had repeat CBCs. Data analysis of the hematocrit values of the first 78 (after which hemoglobin was chosen over hematocrit to identify anemia) showed values ranging from 31.6 to 44.1. The mean hematocrit was 39.8 (median 40.3, standard deviation of 2.58, and variance 6.67). The change from the previous hematocrit to the repeat hematocrit ranged from 5.8 (ie, hematocrit increased from 36.3 to 42.1) to −7.7 (hematocrit decreased from 39.3 to 31.6). The mean change was −0.37 (ie, a decrease of 0.37, median 0.6, standard deviation 2.67, variance 7.14, significance 0.229). Thus, at a “population level,” there was no difference in the repeat hematocrit values (ie, about the same proportion were slightly low and the average repeat hematocrit remained slightly low).
The age of the predominantly male population increased during their time in metals surveillance programs such that the average age changed from the 40- to 49-year age group to 50- to 59-year age group. Using the SPSS One-Sample t test, the difference between US male population hematocrit drop of 1 (between the average hematocrit of the 40- to 49-year and 50- to 59-year-age groups) and the worker population drop of 1.1 was not significant (0.536).
Of the 10 workers not enrolled in a metal surveillance program who had their blood analyzed by both the local naval hospital laboratory and a private local laboratory, 3 had hematocrit values less than 40 (the lower limit of normal) as reported by the naval hospital laboratory; the private laboratory reported all 10 hematocrit levels as greater than 40. Blood samples from an 18 additional workers not enrolled in metals surveillance were sent to the two labortories and analyzed for both hemoglobin and hematocrit. All hemoglobin values from both laboratories were within normal limits (mean values identical at 15.0, and no paired values differed by more than 0.3), but the naval hospital laboratory reported 3 of the 18 hematocrit values as less than 40, while all private laboratory reported values were greater than 40. The discussion with the pathologist prompted by the discrepancy between the in-house and private laboratories revealed that the hematocrit reported by each laboratory was a derived (calculated) value, and that hemoglobin was measured directly.
Although there was very slight variation between laboratories in individual values, the mean values were the same; none of the 18 would have been classified as anemic using hemoglobin (reported by either laboratory) as the criterion. Hematocrit mean values differed by 2, however, and using hematocrit (reported by the local naval hospital but not by the external lab) would have resulted in classifying 3 of 18 persons as anemic.
The results of PBZ sampling for Cr+6, total Cr, SrCrO4, and Cd performed by local industrial hygienists are displayed in Table 2.
Notably, among all workers with elevated PBZ levels of Cr+6, total Cr, SrCrO4, or Cd, only one had anemia. That worker had elevated PBZ SrCrO4 and donated blood; follow-up in that individual was done by his private health care provider, and results were not available to the authors.
The worksite walk-through identified practices requiring modification. Upholstered chairs were found in areas where metal dusts and fumes were produced. Food and drink were noted in work areas. Isolation hoods were too small for some aircraft parts where dust was being generated. Pedestal fans were placed such that floor dust was mobilized and exhaust-venting efficiency was decreased. Most of these practices were corrected immediately, so that work exposures did not remain constant during the investigation.
Wipe samples from multiple surfaces analyzed for 16 metals documented the presence of metals in the workplace, both in work and break areas. For illustration purposes, results from 5 of 54 locations are displayed in Table 3.
Findings for those workers who chose to be evaluated by the OEM physician or who communicated results of evaluations by their private health care providers are listed in Table 4.
In all 11 workers for whom blood and urine Cr levels were obtained, the results were within normal limits. Blood and urine Cd levels were also normal in 17 anemic workers. Six workers had elevated As in their heavy metal screens, although the workers did not work around As. None of the 6 had evidence of marrow suppression; 2 had elevated 24-hour urine As (total) levels (one was very high and the other was minimally elevated). Both were sent to their personal physicians for further evaluation.
The prevalence of anemia found in an apparently healthy workforce seems remarkable. Laboratories would be expected to base a normal range on two standard deviations above and below the mean for healthy persons at that laboratory. Thus, the prevalence of anemia in a healthy workforce could be expected to be approximately 2.5%. However, the MRF workforce, although apparently healthy, was not entirely so. While some workers with underlying conditions could be expected, the proportion (over 16%) of workers with anemia was not expected by the physicians involved with the investigation. With the aging of the workforce, similar findings (anemia or other medical conditions) in the near future may be anticipated. If economic conditions force people to delay retirement, the effect would be magnified.
According to National Health and Nutrition Examination Survey data, in males the change from the 40- to 49-year age group to the 50- to 59-year age group is accompanied by a hematocrit drop of approximately 1 point (45 to 44), thought primarily related to testosterone levels.12 Thus, although the mean hematocrit level of the study population was slightly low, the decline in hematocrit with age was consistent with US population data.
The “nonmetals workers” who served as control groups (of 10 and 18 people, using only the criteria, “works at MRF and not in metals surveillance,” ie, not exposed) helped to identify a systemic error in classifying workers as anemic. Although many medical students learn to “spin a crit,” one can no longer assume hematocrit values are directly measured. The modern equipment used at the local naval hospital and at the outside laboratory measures hemoglobin spectrophotometrically; hematocrit is then calculated using one of several commonly used formulas. Interestingly, the hemoglobin values from both labs for the control groups were almost identical; using local naval hospital hematocrit values overclassified workers as anemic.
As there was no arsenic found at the worksite and the arsenic was not speciated, the source of arsenic exposure for the 2 workers with high urine total arsenic could not be determined. The most likely source was thought to be seafood or contaminated groundwater (both common in coastal northeast Florida). Elevated urine arsenic from seafood is usually thought to be of no clinical significance. One of the workers had exceptionally high urine arsenic level. Attributing the etiology of mild anemia solely to arsenic in one or both of those workers may not be correct.
Although the Navy Cr+6 and Cd surveillance programs require a CBC, it is unclear how (or, possibly, whether) anemia in humans is related to occupational exposure to those metals. Cr picolinate is a component of some vitamins, and, while it may cause anemia with excessive ingestion, we are not aware that there is any known relationship between that and occupational Cr+6 exposure. We have not identified with certainty the basis for including a CBC in Cr+6 and Cd medical surveillance; a 1981 National Institute for Occupational Safety and Health publication that recommended a CBC for Cr+6 surveillance is likely, although it mentions leukocytosis, leukopenia, and monocytosis, but not anemia.13 Chromium has been found to compete with Fe for binding to transferrin and impairs Fe metabolism and storage; in animals, the reduced Fe, Fe binding capacity, and ferritin correlated with reduced hemoglobin.14,15 However, in children receiving parenteral nutrition, although elevated serum Cr was shown to correlate inversely with serum Fe, hemoglobin values did not diminish.16 We are aware of a single animal study that found anemia that ameliorated with time with exposure to Cr.17 Anemia from Pb or arsenic exposure is well documented. Anemia related to Cr or other metals is less well-understood. If occupational Cr+6 exposure causes anemia (and we are not aware of studies to support that), how likely it is to do so without causing other findings, such as nasal irritation, ulceration, or perforation, asthma, irritant or allergic contact dermatitis, and chrome holes, is unknown. What may or may not be related to Cr+6 exposure are the 6 workers with “anemia resolved, no etiology determined.” If Cr causes a transient anemia in animals, does it do so in humans? If so, we cannot be certain whether the “resolved” anemia was related to occupational or other factors or laboratory variation.
Blood Cr levels were normal in the current investigation. Nonstainless steel needle venipuncture may be required when elevated Cr levels are followed, as Cr in the stainless steel may result in spurious results, although the magnitude and significance of that effect is not established.18,19 Interpreting results also is problematic, as normal values are not well-established.
The lack of strong evidence linking Cr+6 and Cd occupational exposure to anemia suggests that the Navy requirement to obtain a CBC for Cr+6 and Cd workers should be reconsidered. Other surveillance methods (ie, the history, physical, urinalysis, or other laboratory test) may identify overexposure sooner or more reliably.
An area for further study is examining the prevalence of various medical conditions (whether actual disease or laboratory abnormalities) among an apparently healthy workforce as it ages. This would be important both for worker health (eg, if the prevalence of worker hypertension increases, more workers should take medication) and for surveillance (if anemia becomes more prevalent, perhaps other or additional tests should be done to improve sensitivity and specificity).
Limitations of the current investigation include incomplete medical findings on workers, particularly those followed up by their personal health care providers from which feedback was not received, and uncertainty as to whether occupational exposures contributed to the anemia of workers with ready explanations for their anemia (eg, hypopituitarism, chronic renal failure). Workers with normal initial CBC values were not rechecked. Thus, if almost 9% of workers had anemia that resolved, it cannot be excluded that some initial CBC values were either inaccurate or that more workers with transient anemia would be identified with more repeat CBC testing.
Finding an unexpected number of anemic workers posed a challenge to the busy OEM physician. Although there were work practices identified as requiring improvement among the Cr+6 workers, there did not appear to be an obvious cause of anemia. In addition to a meticulous and thorough review of cases, it was apparent that assistance was needed. The support from local and remote professionals provided practical help with worksite and worker evaluation, statistical analysis, hypothesis generation, and reassurance.
In summary, the occupational medical surveillance program, a critical part of the multidisciplinary approach to the prevention of work-related illness and injuries, “worked.” It identified a potential trend at the MRF, evaluated it expeditiously, and by using a multidisciplinary approach, several workplaces within the MRF are now safer and healthier for the worker, and several workers are now being treated and followed by their personal physicians for newly-diagnosed health issues.
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