The effect of diabetes on 4-year changes of hearing thresholds in male workers exposed to noise in a single company: a longitudinal study.

BACKGROUND: Recently, several studies have assessed the association between diabetes and hearing impairment. However, the effect of diabetes on hearing impairment is not well known in diabetic patients exposed to noise, a typical cause of hearing impairment. The aim of this study is to longitudinally analyze the effect of diabetes on hearing impairment in workers exposed to similar noise levels from 2013 to 2017 who had experienced little change in their working conditions. METHODS: The study subjects included 2,087 male workers exposed to noise in a single company and who underwent health examinations at the same hospital in Ulsan city in 2013 and 2017. Hearing impairment was defined that a pure-tone average of pure-tone audiometry (PTA) thresholds at 1,000, 2,000, 3,000, and 4,000 Hz was 25 dB and over in both ears. Statistical analyses were conducted using χ2 tests, ANOVA, and Cox proportional hazard models. We analyzed covariates that might affect hearing impairment, including age; working period; levels of total cholesterol, triglyceride, and serum creatinine; smoking and alcohol history; and noise level. RESULTS: The average PTA thresholds and their average changes between 2013 and 2017 were significant in the diabetes mellitus (DM) group than those in the normal and impaired fasting glucose group. Among the subjects with the same status of fasting glucose group in 2013 and 2017, the adjusted hazard ratios for incident hearing impairment among those in the DM group compared to normal group were 3.35 (95% confidence interval [CI], 1.54-7.29) in the left ear and 5.66 (95% CI, 2.01-15.98) in the right ear. CONCLUSIONS: This study suggested that the risk of hearing impairment in the DM group was significantly higher than that in the normal group in both ears, even when exposed to similar noise levels.

Arsenic levels in the groundwater of Korea and the urinary excretion among contaminated area.

Drinking water is a main source of human exposure to arsenic. Hence, the determination of arsenic in groundwater is essential to assess its impact on public health. Here, we report arsenic levels in the groundwater of 722 sites covering all six major provinces of Korea. Water was sampled in two occasions (summer, 722 sites and winter, 636 sites) and the arsenic levels were measured with highly sensitive inductively coupled plasma-mass spectrometry method (limit of detection, 0.1 µg/l) to encompass the current drinking water standard (<10 µg/l). Seasonal variation was negligible, but the geographical difference was prominent. Total arsenic in groundwater ranged from 0.1 to 48.4 µg/l. A 88.0-89.0% of sites were <2.0 µg/l and the remaining ones generally did not exceed 10 µg/l (6.4-7.0%, 2.0-4.9 µg/l; 2.4-3.0%, 5.0-9.9 µg/l). However, some areas (1.0-9.2%) exhibited >10 µg/l. Notably, urinary arsenic excretion of people around these regions was markedly higher compared with non-contaminated areas (<5 µg/l) (79.7±5.2 µg/g (N=122) vs 68.4±5.4 µg/g (N=65) creatinine, P=0.052). All stratified analysis also revealed higher urinary excretion, where a statistically significant difference was noted for non-smokers (85.9±12.7 vs 54.0±6.3, P=0.030), suggesting that arsenic-contaminated groundwater may contribute to its systemic exposure.

Relationship of cigarette smoking and hearing loss in workers exposed to occupational noise.

OBJECTIVES: To investigate the effects of smoking on hearing loss among workers exposed to occupational noise. METHODS: From the results of a special workers health examination performed in 2011, we enrolled 8,543 subjects exposed to occupational noise and reviewed the findings. Using self-reported questionnaires and health examination results, we collected data on age, smoking status, disease status, height, weight, and biochemistry and pure tone audiometry findings. We divided the workers into 3 groups according to smoking status (non-smoker, ex-smoker, current smoker). Current smokers (n = 3,593) were divided into 4 groups according to smoking amount (0.05-9.9, 10-19.9, 20-29.9, ≥30 pack-years). We analyzed the data to compare hearing thresholds between smoking statuses using analysis of covariance (ANCOVA) after controlling for confounder effects. RESULTS: According to ANCOVA, the hearing thresholds of current smokers at 2 k, 3 k, and 4 kHz were significantly higher than that of the other groups. Multiple logistic regression for smoking status (reference: non-smokers) showed that the adjusted odds ratios of current smokers were 1.291 (95% confidence interval [CI]: 1.055-1.580), 1.180 (95% CI: 1.007-1.383), 1.295 (95% CI: 1.125-1.491), and 1.321 (95% CI: 1.157-1.507) at 1 k, 2 k, 3 k, and 4 kHz, respectively. Based on smoking amount, the adjusted odds ratios were 1.562 (95% CI: 1.013-2.408) and 1.643 (95% CI: 1.023-2.640) for the 10-19.9 and ≥30 pack-years group, respectively, at 1 kHz (reference: 0.05-9.9 pack-years). At 2 kHz, the adjusted odds ratios were increased statistically significantly with smoking amount for all groups. At all frequencies tested, the hearing thresholds of noise-exposed workers were significantly influenced by current smoking, in particular, the increase of hearing loss at low frequencies according to smoking amount was more prevalent. CONCLUSIONS: Current smoking significantly influenced hearing loss at all frequencies in workers exposed to occupational noise, and heavier smoking influenced low-frequency hearing loss more greatly. There was a dose-response relationship between smoking amount and low-frequency hearing thresholds; however, this was not observed for high-frequency hearing thresholds. Therefore, well-designed prospective studies are needed to clarify the effects of smoking on the degree of hearing loss.

Cohort study for the effect of chronic noise exposure on blood pressure among male workers in Busan, Korea.

OBJECTIVE: It has not yet been established whether exposure to chronic noise induces an increase in blood pressure or an increase in the development of hypertension. Therefore, a cohort study was performed to identify the effects of chronic noise exposure on blood pressure. METHODS: Five hundred thirty male workers at a metal manufacturing factory in Busan, Korea, were enrolled in the study. They were monitored with an annual health check-ups for nine consecutive years from 1991 to 1999. The subjects were divided into four groups which were determined by noise level categories (NLCs) according to the exposure of noise intensity; NLC-I: office workers who were exposed to <60 dBA at work; NLC-II: worksite technical supporters or inspectors who were intermittently exposed to noise and were not using hearing protection devices; NLC-III: worksite workers exposed to a noise below 85 dBA (TWA) and used one type of hearing protection device, earplug or earmuff; NLC-IV: worksite workers who were exposed to a noise level of 85 dBA or higher in average and used both earplug and earmuff. RESULTS: After controlling the possible confounders, such as baseline age, smoking, alcohol intake, exercise, family history of hypertension, systolic blood pressure (SBP), or diastolic blood pressure (DBP), and changes in body mass index (BMI), we determined that the mean values for the SBP over the duration of this study were 3.8, 2.0, and 1.7 mmHg higher in groups NLC-IV, NLC-III, and NLC-II, respectively, in comparison to that of the NLC-I group. There was no significant difference in DBP among the groups. CONCLUSION: This study suggests that chronic noise exposure increases SBP independently, among male workers.

Arsenite-enhanced procoagulant activity through phosphatidylserine exposure in platelets.

Numerous epidemiological studies have reported the close relationship between arsenic in drinking water and cardiovascular disease (CVD), yet the exact mechanism underlying this relationship remains unclear. We investigated whether arsenic can affect the procoagulant activity of platelets, which are essential in blood clotting, thrombus formation, and progression of CVD. While arsenite alone did not induce procoagulant activity, it significantly enhanced thrombin-induced procoagulant activity of human platelets in a concentration- and time-dependent manner. In flow cytometric analysis, arsenite potentiated phosphatidylserine (PS) exposure and microparticle (MP) formation, the major mediators of procoagulant activity. Arsenite-enhanced calcium increase and subsequent calpain activation were found to be involved in these effects, as determined by confocal microscopy and gel electrophoresis. Arsenite also inhibited flippase, an enzyme that restores PS to the inner leaflet, suggesting that PS could be retained in outer membranes after exposure. Consistent with these in vitro results, ex vivo studies revealed that PS exposure in platelets was significantly increased after acute or chronic arsenic exposure in rats. Most notably, in a rodent in vivo venous thrombosis model, arsenite indeed led to increased thrombus formation. In conclusion, arsenite-enhanced procoagulant activity in platelets by PS exposure and MP generation ultimately results in accelerated thrombus formation in vivo, suggesting that this enhanced activity is a possible contributing factor in CVD associated with chronic exposure to arsenic through drinking water.

Comparison of disability duration of lumbar intervertebral disc disorders among types of insurance in Korea.

The incidence of work-related musculoskeletal disorder including low back pain sharply increased since 2000 in Korea. The objectives of the present study are to compare disability duration of lumbar intervertebral disc displacement among types of insurances, and to obtain its appropriate duration. The medical records of all patients whose final diagnosis in discharge summary of chart was lumber specified intervertebral disc displacement (LIVD) in 6 large general hospitals in Korea were reviewed to compare the length of admission and disability among different types of insurances. The information on age, gender, the length of admission, the length of follow-up for LIVD, occupation, operation, combined musculoskeletal diseases, and type of insurance was investigated. 552 cases were selected and analyzed to calculate arithmetic mean, median, mode, and geometric mean of disability duration. There was a significant difference in the length of admission and disability among types of insurance after controlling covariates such as age and combined diseases by the analysis of covariance. The length of admission in cases of IACI and AI was much longer than that of HI, and the length of disability in cases of IACI was much longer than that of HI. Prolonged duration of admission and disability was not assumed due to combined diseases, complication or other unexplainable personal factors in cases of those with industrial accidents compensation insurance and automobile insurance. This means that proper management of evidence-based disability duration guidelines is urgently needed in Korea.

Inorganic arsenite potentiates vasoconstriction through calcium sensitization in vascular smooth muscle.

Chronic exposure to arsenic is well known as the cause of cardiovascular diseases such as hypertension. To investigate the effect of arsenic on blood vessels, we examined whether arsenic affected the contraction of aortic rings in an isolated organ bath system. Treatment with arsenite, a trivalent inorganic species, increased vasoconstriction induced by phenylephrine or serotonin in a concentration-dependent manner. Among the arsenic species tested--arsenite, pentavalent inorganic species (arsenate), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV)--arsenite was the most potent. Similar effects were also observed in aortic rings without endothelium, suggesting that vascular smooth muscle plays a key role in enhancing vasoconstriction induced by arsenite. This hypercontraction by arsenite was well correlated with the extent of myosin light chain (MLC) phosphorylation stimulated by phenylephrine. Direct Ca2+ measurement using fura-2 dye in aortic strips revealed that arsenite enhanced vasoconstriction induced by high K+ without concomitant increase in intracellular Ca2+ elevation, suggesting that, rather than direct Ca2+ elevation, Ca2+ sensitization may be a major contributor to the enhanced vasoconstriction by arsenite. Consistent with these in vitro results, 2-hr pretreatment of 1.0 mg/kg intravenous arsenite augmented phenylephrine-induced blood pressure increase in conscious rats. All these results suggest that arsenite increases agonist-induced vasoconstriction mediated by MLC phosphorylation in smooth muscles and that calcium sensitization is one of the key mechanisms for the hypercontraction induced by arsenite in blood vessels.

Neurobehavioral changes of shipyard painters exposed to mixed organic solvents.

This study was conducted to evaluate neurobehavioral changes arising from occupational exposure to organic solvents among shipyard painters and to establish whether a dose-effect relation existed where there was any observed impairment of neurobehavioral performance by running the test of Simple Reaction Time (SRT), Symbol Digit Substitution (SD), and Finger Tapping Speed (FT) with a computer-assisted neurobehavioral test battery. The study group consisted of 180 shipyard painters and 60 reference workers. The workers answered a self-administered questionnaire on occupational, medical history, and demographic characteristics including age, work duration, education level, and quantity and frequency of alcohol and smoking, and performed three psychometric tests on the Korean Computerized Neurobehavioral tests. To estimate cumulative exposure level, samples of ambient air on 61 painters were analyzed using a gas chromatograph. Shipyard painters and the reference group showed significant differences in the results of test of SD, FT of dominant hand, and FT of non-dominant hand. The test results of SD of shipyard painters also showed significant difference by duration of work. This suggests that occupational exposure of organic solvent could induce neurobehavioral changes in the shipyard painters. Therefore an objective neurobehavioral tests recommended on evaluating neurobehavioral performance of long-term solvent-exposed shipyard workers.

Occupational hand-arm vibration syndrome in Korea.

OBJECTIVES: It is suspected that there is a large number of patients suffering from hand-arm vibration syndrome (HAVS) in Korea. However, no cases have been reported since 1992. This study was conducted to identify HAVS cases and determine the characteristics of the syndrome. METHODS: In April 2001, the Busan, Ulsan, and Gyeong-Nam Province Occupational Disease Surveillance System (BUGODSS) was established to identify work-related HAVS and other occupational diseases. In the 2 years of this project, occupational physicians from five hospitals in these provinces collected information by way of interviews and questionnaires during mandatory occupational medical examinations. Among the initial 189 suspected HAVS cases, 58 volunteers were given cold-water provocation tests in order to diagnose the vascular component of the disorder. RESULTS: One hundred fifty-four approximately occupational HAVS cases were identified from ca. 21,000 workers. One hundred fifty about of these cases were male. The cases were most often found in workers from the shipbuilding industry, and the grinder was the most common source of vibration exposure. Cases of sensorineural disorder (SD) were more common than cases of vascular disorder (VD). The mean values of the finger skin temperature and its recovery rate at 5 min and 10 min after cold-water provocation were significantly lower in the group with the VD than in the group with the SD. CONCLUSIONS: We identified 154 occupational HAVS cases, although no cases have been reported during the occupational medical examinations mandated by the state. The majority of the cases were in workers that used grinders in the shipbuilding industry. We determined that peripheral VD and peripheral SD can progress independently of each other. We conclude that exposure to hand-transmitted vibration (HTV) and HAVS cases are common in shipbuilding industry in Korea. The recovery rate of finger skin temperature after cold-water provocation is one of the useful methods for diagnosing the vascular component of HAVS.

Whole blood and red blood cell manganese reflected signal intensities of T1-weighted magnetic resonance images better than plasma manganese in liver cirrhotics.

We examined whole blood (MnB), red blood cell (MnRBC), plasma (MnP) and urinary Mn (MnU) concentrations in 22 liver cirrhotics and 10 healthy controls to evaluate Mn concentration in which a fraction of biological samples best reflects pallidal signal intensities (pallidal index; PI) on T1-weighted magnetic resonance images (MRI) in liver cirrhotics. Increased signal intensity in the globus pallidus was observed in 18 (81.8%) of the 22 patients with liver cirrhosis. In a transplanted patient, increased pallidal signals also resolved as his liver function tests normalized after liver transplantation. There were significant correlations between MnB/MnRBC and PI (rho=0.529, rho=0.573, respectively) in liver cirrhotics, although no significant correlation was observed between MnP/MnU and PI. According to a multiple linear regression, MnB and MnRBC reflected the signal intensities of T1-weighted MRI better than MnP or MnU.

Blood manganese concentration is elevated in iron deficiency anemia patients, whereas globus pallidus signal intensity is minimally affected.

OBJECTIVES: To determine whether blood manganese (Mn) concentration is elevated in patients with iron deficiency anemia (IDA), and whether this affects signal intensities in the globus pallidus. METHODS: Twenty-seven patients with IDA and 10 control subjects were tested for blood Mn, and brain magnetic resonance images (MRI) were also examined. Seventeen of the 27 patients were followed-up after iron therapy. RESULTS: IDA patients had a mean blood Mn concentration of 2.05 +/- 0.44 microg/dl, which was higher than controls. The mean pallidal index (PI) of anemic patients was not different from that of controls. There was a correlation between log blood Mn and PI (rho = 0.384, P = 0.048; n = 27) in IDA patients. None of the patients showed increased signals in the globus pallidus in T1-weighted MRI. Blood Mn levels decreased and hemoglobin levels increased after iron therapy (P < 0.05). CONCLUSION: Although blood Mn is elevated in IDA patients, there is no increase in globus pallidus MRI signal intensity. These findings stand in contrast to those of our other studies showing patients with chronic liver disease or occupational Mn exposure have elevated signal intensities remarkably.

CDNA array analysis of gene expression profiles in brain of mice exposed to manganese.

This study is performed to detect changes of gene expression in substantia nigra (SN) and striatum in manganese (Mn)-exposed mice brain. The cDNA array is a recently developed molecular biological method that can detect the differential expression of several hundreds of genes simultaneously and is therefore advantageous in the study of trace metal intoxication effect at the genetic level. Using this technology, we discovered 5 genes in the mouse striatum and 9 genes in SN changed by more than 50% following Mn exposure. Depression were observed in two genes (neural cell adhesion protein BIG2, heavy neurofilament subunit genes) in striatum and three genes (light neurofilament subunit, brain acyl-CoA synthetase II, heavy neurofilament subunit genes) in the SN. However three genes (N-acetylglucosaminyltransferase I, S100beta, and synaptonemal complex protein I genes) in striatum and six genes (noggin, striatin, Ost oncogene, S100beta, calcium/calmodulin-dependent protein kinase kinase beta, and N-acetylglucosaminyltransferase I genes) in SN were elevated following Mn exposure. Immunohistochemical study revealed that protein levels of S100beta also increased following Mn treatment. Activated astrocytes overexpressing S100beta are invariably and intimately associated with decreased expression of heavy and light neurofilament subunits which is a distinguishing feature of neurodegeneration by Mn exposure. All our findings suggested that neuronal degenerations occur in SN as well as striatum of mice exposed to Mn.

Calcification mimicking manganese-induced increased signal intensities in T1-weighted MR images in a patient taking herbal medicine: case report.

Characteristic high signal intensities confined to the globus pallidus on T1-weighted magnetic resonance image (MRI) can be observed in manganese (Mn)-exposed workers, however, these high signals should be differentiated from those due to other causes such as fat, hemoglobin breakdown products, melanoma, neurofibromatosis, and calcification. A 39-year-old woman was admitted with mutism and involuntary movements which had developed the day before. She had ingested two packs of liquid herbal medicine containing 0.53 mg of Mn daily for 4 months prior to visiting our hospital. Her MRI showed high signals, confined mainly to the globus pallidus on T1-weighted images. Follow-up brain MRI at an interval of 11 months showed no interval change. Brain computed tomography (CT) at the time of the second MRI showed symmetric calcification on both globus pallidus. Blood levels of liver function tests, calcium, phosphorus, and parathyroid hormone were within normal ranges. The increased signals, which were first presumed to be induced by Mn, were concluded to be due to calcification based on the following reasons. First, follow-up brain MRI at an interval of 11 months did not show any interval change. Second, the ingested amount of 1.06 mg Mn daily for 4 months is even less than that added to mineral supplements for adults. Third, Mn-induced high signals in T1-weighted MRI do not show any abnormal findings in brain CT. The present case report suggests that brain CT should be performed to rule out symmetric calcification on basal ganglia in patients showing increased signals in T1-weighted MRI, but who do not have a significant exposure history to Mn. The present report also showed that the amount of 1.06 mg Mn daily ingested for 4 months did not cause the high signal in brain MRI.

Whole blood manganese correlates with high signal intensities on T1-weighted MRI in patients with liver cirrhosis.

We examined whole blood (MnB), plasma (MnP) and urinary Mn (MnU) concentrations in 33 cirrhotics and 11 healthy controls to clarify: (1) whether, in chronic liver diseases, MnB or MnP reflects pallidal signal intensities in magnetic resonance imaging (MRI); and (2) which factors in chronic liver diseases correlate with pallidal signal intensities in T1-weighted MRI. Increased signal intensity in the pallidum was observed in 27 (81.8%) of 33 patients with liver cirrhosis in T1-weighted MRI. There was a significant correlation between MnB and pallidal index (PI) (gamma = 0.559, P < 0.01) in the patients. However, no significant correlation was observed between MnP and PI (gamma = 0.353, P > 0.05). According to a multiple linear regression, MnB reflected the signal intensities of T1-weighted MRI better than MnP or MnU. Child/Pugh score and total bilirubin level also correlated with PI. However, the hemoglobin level did not correlate with PI significantly.

Effect of manganese exposure on MPTP neurotoxicities.

We used a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice model to evaluate whether manganese (Mn) exposure can affect MPTP-induced neurotoxicity. We randomly assigned adult male C57BL/6 mice (n=5-7 per group) the following treatments: SO, Mn(-) x MPTP(-); MO, Mn(+) x MPTP(-); SM, Mn(-) x MPTP(+); MM, Mn(+) x MPTP(+). Mn (MnCl(2).4H(2)O) was administered intraperitoneally at a dose of 2 mg/kg daily for 3 weeks. MPTP was then administered intraperitoneally at a dose of 30 mg/kg daily for 5 days in the SM and MM groups. Seven days after the last MPTP injection, the animals were sacrificed. Blood Mn levels were elevated in the Mn-exposed groups. Striatal Mn levels were not influenced by Mn treatment alone, however, they were decreased following MPTP. Tyrosine hydroxylase (TH)-immunoreactive (ir) neurons in the substantia nigra pars compacta (SNpc) were decreased significantly in the MPTP-exposed groups. Densities of TH- and dopamine transporter (DAT)-ir axon terminals in the caudate-putamen (CPU) were also decreased in the MPTP-treated groups. Furthermore, glial fibrillary acidic protein (GFAP)-ir astrocytes increased in the CPU with MPTP treatment. However, no effects were observed with Mn exposure. Concentrations of dopamine (DA), 3,4-dihydrophenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the corpus striatum were also decreased significantly with MPTP treatment alone, but Mn had no effect. Thus, decreased dopaminergic activities with MPTP led to decreased DA and its metabolites. Significant hypertrophies of GFAP-ir astrocytes in the globus pallidus (GP) were observed in Mn-exposed groups, especially in the MM group. MPTP targeted dopaminergic systems whereas Mn neurotoxicities occurred in the GP. In conclusion, our data suggest that Mn does not potentiate the neurotoxicity of MPTP.

Hematological changes of children exposed to volatile organic compounds containing low levels of benzene.

We conducted a cohort study to evaluate the hematological changes of children environmentally exposed to volatile organic compounds (VOCs). The study subjects comprised 192 children who consisted of 97 children living near a petrochemical estate region and 95 children living in a suburban region of Ulsan, Korea. We executed the hematological examination three times, in April, July and October. A generalized linear model analysis was used to test for changes over time in the complete blood count (CBC) values of each study group. All CBC values of children showed differences between regions in accordance with the survey month. In the model, region was a significant independent variable for the total white blood cell, red blood cell, and platelet. This suggests that the amounts of exposure to VOCs are different between study groups in different months, and environmental exposure to VOCs is associated with a higher prevalence of hematological abnormalities. Hematological abnormalities in children exposed to VOCs containing low levels of benzene could serve as a biological marker of atmospheric VOCs.

Nasal septum perforation of welders.

During the periodic physical checkups in 1997-2000, the authors have found eleven cases of nasal septum perforation among 2,869 welders in Ulsan, Korea. They have not suffered from diseases and conditions that could cause septum perforation such as tuberculosis, syphilis, and long-term use of topical corticosteroids. And also they did not have trauma history and surgical experiences on their nasal septum. To investigate the cause of septum perforation we reviewed the past history of pre-employment, the results of annual working environment survey and the material safety data sheets of welding rods and steels with which they have dealt. We also analyzed the concentration of several metals of welding fume and the concentration of blood and urinary chromium. In the result, we assumed that the nasal septum perforation of welders was due to chronic exposure to low-level hexavalent chromium.

Evaluation of activity of erythrocyte pyrimidine 5'-nucleotidase (P5N) in lead exposed workers: with focus on the effect on hemoglobin.

Anemia that accompanies lead poisoning is in part the result of various inhibitory effects of lead on heme biosynthesis. Lead also increases the rate of red blood cell destruction due to the profoundly depressed activities of erythrocyte pyrimidine 5'-nucleotidase (P5N) activities. We studied parameters of the two metabolic pathways in the workers exposed to lead to evaluate P5N in the lead exposed workers and which pathway has an effect on hemoglobin (Hb) level. 29 male workers in the secondary lead smelting as high exposure group, 46 male workers in the manufacturer of inorganic pigment as low exposure group and 56 clerical male workers from another plant as non-exposed group were studied. Activity of P5N, lead concentration in whole blood (PbB), zinc protoporphyrin (ZPP), Hb, and ferritin were determined. In the present study, P5N activity of nucleotide metabolic pathway correlated with Hb after controlling indices of iron deficiency anemia (ferritin) occurring concurrently and heme biosynthetic pathway (ZPP) in the high exposure group while heme biosynthetic pathway did not correlate with Hb after controlling other two variables in exposure groups. These findings suggest that P5N rather than heme biosynthetic pathway has a major effect on Hb level even in workers without manifest hemolytic anemia.