Core 20 - Rosemarie Bowler

Core 20 - Rosemarie Bowler

Manganese Health Research Program: Phase 2, Core 20

Research Core Project Number:  
Research Core Project: Longitudinal Study of Health Effects Over 3 Yrs in Mn Exposed Bridge Welders
Core Principal Investigator (CPI): Dr. Rosemarie Bowler
San Francisco State University
8371 Kent Dr.,
El Cerrito, CA 94530, U.S.A.
Phone: 510-236-5599
Fax: 510-236-3370
E-mail: rbowl@sfsu.edu
Key Collaborators:

Dr. Harry A. Roels
Louvain Centre for Toxicology and Applied Pharmacology
Université catholique de Louvain (Brussels)
Pauwelslaan 3
3271 Averbode,
Belgium

Dr. Long Ngo
General Medicine (Biostatistics)
Beth Israel Deaconess Medical Center 
Harvard School of Medicine
330 Brookline Ave.
Boston, MA 02215, U.S.A.

Dr. Jayne Wilkinson
Philadelphia Parkinson’s Disease Research, Education and Clinical Center
3900 Woodland Ave.
Philadelphia, PA 19104, U.S.A.

Dr. Nadia Abdelouahab
University of Sherbrooke
Sherbrooke, Québec- Canada

Robert Park
Education and Information Division
CDC/NIOSH
4676 Columbia Parkway, C-15
Cincinnati, OH 45226, U.S.A.

Project Objectives:

  • To evaluate Mn-exposed welders’ general cognitive, mood, and motor function 3 ½  years later, at a follow-up  in 2008 after baseline testing in January 2005. A brief screening was completed after 15 months in 2006.
  • To evaluate blood levels of manganese and lead at follow-up
  • To evaluate and compare welders’ olfaction, sleep and sexual function from baseline to follow-up.
  • To evaluate welders’ respiratory status at baseline and follow-up

Project Description:

Brief abstract describing scope of project

This study was designed to follow-up a group of 43 confined space welders of the San Francisco Bay Bridge, first studied in January 2005 (Park et al., 2006; Bowler et al., 2007). This baseline study revealed neurological, cognitive/neuropsychological, and neurophysiological (sensory/autonomic) adverse effects which showed significant dose-effect associations with the Mn concentration in whole blood (Mn-B) and/or a cumulative Mn exposure index (CEI) (Bowler et al., 2007).  Their exposure to Mn, unprotected and with poor ventilation lasted on average for 16.5 months. The mean TWA of Mn-air ranged from 0.11-0.46 mg/m³ and the frequency above Cal-OSHA TLV of 0.20 mg/m³ was 55% (88 samples out of 159 total non-short-term air samples). A further study of these welders investigated the exposure-response relationship and risk assessment for cognitive deficits in early welding-induced manganism (Park et al., 2010). After the MHRP funding became available, the Bay Bridge welder cohort was re-tested in August 2008 for neuropsychological, neurological, respiratory, and olfactory function. d Despite extensive efforts to contact the forty-three welders, only 37 were reached for re-testing. Of those who could be reached, 26 welders came to their appointments resulting in a response rate of 26/37 (70%). Mostly the same health professionals, neuropsychologists, graduate students, phlebotomist, and pulmonary technician retested these welders using the same test battery. The primary statistical analysis used a general linear model where the dependent variable was the individual-specific difference between 2008 and 2005, and with ethnicity as independent variable. The mean age of the group at follow-up was 47 years with an average of 12.3 years of education. The mean months and total years of welding since baseline was 23 months and 16.9 years, respectively. Only 50% of the follow-up group was ‘currently’ involved in welding procedures.

Welders had significantly lower Mn-B levels at follow-up than at baseline (8.4 vs  10.0 µg/L). Those still welding had significantly higher Mn blood levels (9.9 µg/L) than those no longer welding (6.8 µg/L). The Bay Bridge welder follow-up focused in particular on four neurological functions of which the measured endpoints involve specific brains structures, such as the limbic system (olfaction and mood), the basal ganglia (movement/neuromotor) the frontal cortex and the hippocampus (cognitive/neuropsychological function). Several domains of cognitive functioning improved substantially as shown by large effect sizes for verbal skill, visuospatial memory, visuo-motor processing and tracking speed. Mood disturbance improved only slightly clinically, but complaints of depression and anxiety persisted. Motor dexterity/tactile function (Grooved Pegboard test) and graphomotor tremor improved significantly, while psychomotor speed (Fingertapping) remained unchanged. Most findings of the neurological examination (UPDRS: Unified Parkinson Disease Rating Scale) did not change compared to baseline, whereas rigidity (UPDRS), postural dominant-hand tremor and body sway (CATSYS) worsened. Olfactory and respiratory function scores remained depressed.

In conclusion, this follow-up study of Mn-exposed welders showed mixed results as to the reversibility of adverse CNS findings. After 3.5 years of cessation of confined space welding, only cognitive function improved significantly, while olfactory, extrapyramidal, and mood disturbances remained constant or were exacerbated. This suggests differential intrinsic vulnerabilities of the brain loci involved with Mn exposure. Despite the relative young age of the welders (mean 47 years), both current and ex-welders continued to present with features of Mn-induced parkinsonism. Our findings are in line with the conclusions based on nonhuman primate studies, in that structural and functional disruption of the basal ganglia alone cannot explain the continuum of dysfunctions from psychiatric to cognitive to motor abnormalities associated with Mn exposure (Burton and Guilarte, 2008). Accumulation of Mn in the frontal cortex of nonhuman primates promotes inflammation and cell death and accelerates neurodegenerative changes in that part of the brain, which is postulated to trigger early signs of cognitive deficits (Guilarte et al., 2008). This Bay Bridge welder study highlights a historical lack of compliance with Cal- OSHA’s TLV-TWA for exposure to airborne Mn (0.20 mg/m³) and insufficient surveillance of confined space welding. Coupled with the fact that more than 90% of Mn particulate in welding fume is of respirable size (aerodynamic diameter <10 μm), a more stringent preventive measure is recommended for confined space welding.

References

Bowler RM, Roels HA, Nakagawa S, Drezgic M, Diamond E, Park R, et al. Dose-effect relationships between manganese exposure and neurological, neuropsychological and pulmonary function in confined space bridge welders. Occup Environ Med. 2007;64:167-77.

Burton NC, Guilarte TR. Manganese neurotoxicity: Lessons learned from longitudinal studies in non-human primates. Environ Health Perspect. 2008;117:325-32.

Guilarte TR, Burton NC, Verina T, Prabhu W, Becker KG, Syversen T, et al. Increased APLP1 expression and neurodegeneration in the frontal cortex of manganese-exposed non-human primates. J Neurochem. 2008;105:1948-59.

Park RM, Bowler RM, Eggerth DE, Diamond E, Spencer KJ. Issues in neurological risk assessment for occupational exposures: The Bay Bridge welders. Neurotoxicology. 2006;27:373-84.

Park RM, Bowler RM, Roels H. Exposure-response relationship and risk assessment for cognitive deficits in early welding-induced manganism. J Occup Environ Med. 2009;51:1125-36.

Project Status:

Project started:                       April 15, 2008   
Project completion date:   January 30, 2010  
   

Key research accomplishments:

The study was carried out as planned and data scoring and analyses are now complete.  A presentation of the findings will be presented in a symposium entitled: “Manganese health effects in Welding: Scientific investigation addressing the controversy” at the American Psychological Association convention on August 9, 2009 in Toronto, Canada.  This research has had participation from numerous doctoral and Master’s level students who have learned much about neurotoxicity and its evaluation. Additional analyses on the Latinos in the group are underway and several more manuscripts will be completed.

Publications/Presentations arising from project:

Publication:

Bowler RM, Gocheva, V, Harris M, Ngo L, Abdelouahab N, Wilkinson J, Doty RL, Park R, RoelsHA (2011).  Prospective study on neurotoxic effects in manganese-exposed bridge construction welders.  Neurotoxicology (in press)

doi:10.1016/j.neuro.2011.06.004

Presentations:

1. Society of Toxicology, Washington, D.C., March 6-10, 2011

Symposium session: The use of epidemiological data and PBPK modelling in a risk assessment: manganese as a case study

H.A. Roels (invited presentation): Biomarkers of exposure to manganese and prospective studies of its neurotoxic effects in occupational cohorts.  Abstract #2458.

2. Xi’an International Neurotoxicology Conference, Xi’an, China, June 5-10, 2011Parallel Symposium 12 (ICOH)

Harry A. Roels, Rosemarie Bowler, Perrine Hoet (invited presentation): Occupational exposure to manganese (Mn): reversibility outcome of early Mn-induced neurotoxic effects after decrease of exposure.  Proceedings p.233.

 

Last updated: August 1, 2011


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