Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders

Background

Although adverse neuropsychological and neurological health effects are well known among workers with high manganese (Mn) exposures in mining, ore‐processing and ferroalloy production, the risks among welders with lower exposures are less well understood.

Methods

Confined space welding in construction of a new span of the San Francisco–Oakland Bay Bridge without adequate protection was studied using a multidisciplinary method to identify the dose–effect relationship between adverse health effects and Mn in air or whole blood. Bridge welders (n = 43) with little or no personal protection equipment and exposed to a welding fume containing Mn, were administered neurological, neuropsychological, neurophysiological and pulmonary tests. Outcome variables were analysed in relation to whole blood Mn (MnB) and a Cumulative Exposure Index (CEI) based on Mn‐air, duration and type of welding. Welders performed a mean of 16.5 months of welding on the bridge, were on average 43.8 years of age and had on average 12.6 years of education.

Results

The mean time weighted average of Mn‐air ranged from 0.11–0.46 mg/m³ (55% >0.20 mg/m³). MnB >10 µg/l was found in 43% of the workers, but the concentrations of Mn in urine, lead in blood and copper and iron in plasma were normal. Forced expiratory volume at 1s: forced vital capacity ratios (FEV₁/FVC) were found to be abnormal in 33.3% of the welders after about 1.5 years of welding at the bridge. Mean scores of bradykinesia and Unified Parkinson Disease Rating Scale exceeded 4 and 6, respectively. Computer assisted tremor analysis system hand tremor and body sway tests, and University of Pennsylvania Smell Identification Test showed impairment in 38.5/61.5, 51.4 and 88% of the welders, respectively. Significant inverse dose–effect relationships with CEI and/or MnB were found for IQ (p⩽0.05), executive function (p⩽0.03), sustaining concentration and sequencing (p⩽0.04), verbal learning (p⩽0.01), working (p⩽0.04) and immediate memory (p⩽0.02), even when adjusted for demographics and years of welding before Bay Bridge. Symptoms reported by the welders while working were: tremors (41.9%); numbness (60.5%); excessive fatigue (65.1%); sleep disturbance (79.1%); sexual dysfunction (58.1%); toxic hallucinations (18.6%); depression (53.5%); and anxiety (39.5%). Dose–effect associations between CEI and sexual function (p<0.05), fatigue (p<0.05), depression (p<0.01) and headache (p<0.05) were statistically significant.

Conclusions

Confined space welding was shown to be associated with neurological, neuropsychological and pulmonary adverse health effects. A careful enquiry of occupational histories is recommended for all welders presenting with neurological or pulmonary complaints, and a more stringent prevention strategy should be considered for Mn exposure due to inhalation of welding fume.Manganese (Mn) exposure through welding fume has been reported to cause parkinsonian syndrome, sometimes described as welding fume‐related parkinsonism and often misdiagnosed as Parkinson''s disease because of similarities in neurological features including tremor, masked facies and generalised bradykinesia.¹ However, important differences in movement disturbance between Mn‐induced parkinsonism (also called manganism) and idiopathic Parkinson''s disease (IPD) include an awkward high‐stepping dystonic gait in manganism, which is in stark contrast with the typical shuffling gait in patients with IPD, and the tendency to lose balance by falling backward in IPD and forward in manganism. Additionally, tremor characteristics are different, usually resting tremor in IPD and postural intention tremor in manganism.¹ Magnetic resonance imaging (MRI) may be used to differentiate IPD from Mn‐induced parkinsonism if a patient has had excess Mn exposure within the previous 6 months.² Positive MRIs can show cerebral Mn²⁺ deposition in both animals and humans, especially in the globus pallidus (possibly in the striatum), by exhibiting a T₁‐weighted signal hyperintensity.³ IPD, however, is associated with lesions in the substantia nigra pars compacta, and does not exhibit MRI abnormality in the globus pallidus. Two other key features differentiating between Mn‐induced parkinsonism and IPD are: (1) a younger age of onset for Mn‐exposed workers and (2) little or no response to l‐dopa among Mn‐induced parkinsonism cases.^4,5 Case reports of neurological findings in career welders exposed to Mn have shown dystonia bilaterally in the shoulders and four distal limbs, as well as other parkinsonian features—for example, tremor and postural instability.^5,6Welders have been reported to be exposed to “a wide variety of potential respiratory hazards”,^7,8 although earlier studies did not show increases in chronic bronchitis.⁹ However, shipyard welders have been reported to have a higher standardised mortality ratio for lung cancer, a finding which was also supported by the California Occupational Mortality Survey, after adjustment for smoking and asbestos exposure. Sjögren presented evidence of a causal relationship between exposure to stainless steel welding and lung cancer.¹⁰Diagnosis of Mn intoxication in workers actively exposed to excessive Mn in welding fumes can be further supported by biomarkers of exposure indicating increased internal Mn concentrations—for example, in whole blood and to a lesser extent in plasma/serum or urine. Sjögren et al¹¹ reported a mean concentration of 8.4 μg/l for whole blood Mn (MnB) in welders, whereas in other industrial settings the mean MnB ranged from 8.1 to 25.3 µg/l. No clear cutoff value of MnB is currently agreed upon, but HAR postulates that any values >10 µg/l is of concern.Mn air levels (Mn‐air) as reported in a few welder studies indicate that aerosols in welding operations (external exposure) usually contain <0.5 mg Mn/m³ (total dust), but sometimes they are >1 mg Mn/m³. A paramount feature of welding fume is that most of the airborne particles are in the respirable fraction (particle size <10 µm).¹² It is astonishing that reliable levels of respirable Mn particulate have rarely been reported, given the importance of the pulmonary uptake of Mn via the alveoli and its significance for Mn distribution to and effects on the central nervous system.¹³ It should be pointed out that inhalation exposure to Mn is for most of the jurisdictions regulated on the basis of total (or inhalable) dust: however, in the particular case of welding, a permissible exposure level established on the respirable fraction would enhance health prevention strategies.Neuropsychological testing methods used over the past two decades have successfully differentiated Mn‐exposed welders from unexposed controls.^4,6,11 There have been 13 reports on welders showing deficits for motor, tremor, memory and neurocognitive domains, as well as for sleep, sexual function and vision. Although not all reports dealt with all of these domains, 11 studies indicated slowing of motor speed/efficiency^{4,6,11,14,15,16,17,18,19,20,21} and tremor^{3,4,6,14,15,16,17,19,20,21,22}; eight found loss of neurocognitive functioning^{4,6,11,14,16,18,19,21}; and six reported diminished memory function.^{4,6,11,14,18,21} Six studies reported sleep disturbances^{4,6,11,14,15,17} and three sexual problems.^4,6,14 Vision was assessed in only two studies, and both found loss of colour vision associated with Mn exposure.^6,14Welders exposed to Mn‐containing welding fumes and dust have rarely been investigated by clinical neuropsychologists using an epidemiological study design in which actual measurements of internal and external exposure to Mn are studied in relation to outcome variables of a comprehensive test battery (including measures of IQ). Therefore, in the latter part of 2004, we decided to evaluate a welder group with health complaints, identified as employees on the reconstruction project of the San Francisco–Oakland Bay Bridge, which was damaged during the 1989 earthquake. The work on a vulnerable portion of the East span of the bridge began in 2003, requiring confined space welding of 28 anchoring foundations or piers, consisting of steel piles and footing boxes. The welding operations took place below the Bay''s surface in unpressurised cofferdams. During the first 1.5 years of welding on the support piers for the new bridge, welders began to express concerns of ill health feared to be the result of exposure to fumes due to confined space welding. During this period the welders were not required to wear personal protective equipment, and ventilation was minimal or ineffective. After receiving health complaints from almost 90% of the welders employed on the project, workers'' compensation evaluations were enacted, which supported their report of adverse health effects. A multidisciplinary study group took advantage of this “natural experiment” for undertaking additional clinical evaluations (1) to assess the extent of neurological, neuropsychological, neurophysiological and pulmonary effects, (2) to explore whether these effects were associated with internal and/or external measures of Mn exposure and (3) to define a tentative permissible exposure level for Mn in welding fume.