Neuropsychological and stress evaluation of a residential mercury exposure.

Residents of a former factory building converted to apartments were exposed to mercury over a 2-year period. The neurobehavioral and emotional health effects of this exposure and subsequent evacuation are presented. Urine mercury levels were measured before (urine1) and 3-10 weeks after evacuation (urine2) of the building, when neurobehavioral and psychological measures were also completed. Performance on neurobehavioral and psychologic measures were compared between subjects above and below the median for urine1 (>=19 microg/g creatinine) and were correlated with urine1 mercury levels. The high urine mercury group made more errors on a test of fine motor function and 84% of the residents reported clinically significant elevations in somatic and psychologic symptoms. Although subclinical tremor from mercury exposure may have affected subtle hand-eye coordination, other tests of motor function were not affected. Therefore, the observation of reduced hand-eye coordination may be due to chance. Significant levels of psychosocial stress were more closely associated with the evacuation necessitated by mercury exposure rather than a direct effect of mercury exposure.

acuation are preenti.Urne mer leves were m bfore (urinel) and:3-10 weeks; after e n (e2) ofthe: buMding>;he neubhaviorald psychological measures were: also completed. Performance on neurobehavioral and psychologic measures were compared between subjects above and below the mian for uinel (219 p/g cre e) and were corre- The acute and chronic behavioral effects of mercury in humans have been documented in cases of acute poisoning (1)(2)(3) and epidemiologic studies of occupational exposures (4,5). Adverse neurobehavioral effects of inorganic mercury include reduced cognitive functions (e.g., memory and concentration) and emotional disturbances such as depression, irritability, emotional lability, and fatigue (5,6). Environmental exposures to mercury occur through fish consumption, waste incineration, energy production, and the widespread use of dental amalgams, although the health consequences of these exposures are undear (7)(8)(9).
Nonoccupational community exposures to neurotoxicants are often unexpected and traumatic (10,11). Therefore, the direct neurologic and neurobehavioral effects of exposure may be accompanied by symptoms of trauma and stress. The purpose of the present study was to evaluate neurobehavioral performance and psychological symptoms in response to an elemental mercury exposure that occurred in a community and resulted in the evacuation of residents from their contaminated homes.
A five-story factory building, used to manufacture mercury vapor lamps in the 1930s, was converted to condominium apartments by an artists' cooperative and was occupied in 1994-1995 by the artists and their families. A majority of the occupants used their apartments as both living and working quarters and at least one family member was in the building full-time for approximately 2 years. When the mercury contamination was discovered and reported, average air mercury levels ranged from 5 pg/m3 in adult breathing zones with a peak value of 888 pg/m3 over visible pools of liquid mercury on the floor (12). Air levels in some living quarters exceeded the Occupational Safety and Health Administration permissible exposure limit of 50 pg/m3. Prior to evacuation, 90% (n = 26 of 29) of the residents, including children, had urine mercury levels, normalized to a specific gravity of 1.024, of >20 pg/I (13). Thus, 90% of the residents exceeded the upper limit for an unexposed population. The residents were evacuated to temporary housing paid for by the EPA. After extensive assessment documented the pervasive distribution of mercury, the building was condemned.
In the present study, urine mercury levels were measured both before (urinel) and after (urine2) termination of exposure. Computerized and traditional tests of neurobehavioral function, psychological and somatic symptom reports, and the impact of self-identified stressors were measured as indicators of health effects following evacuation of the dwellings. Medical history and exams were also performed. This study reports on the neurobehavioral effects of an uncommon and unexpected residential exposure, which for many of the residents occurred on a 24-hr basis.

Materials and Methods
Subjects. The 37 residents at risk for mercury exposure in the converted building were referred for evaluation by the Agency for Toxic Substances and Disease Registry (ATSDR) through the Association of Occupational and Environmental Clinics. The protocol for this medical evaluation was developed in collaboration with the ATSDR and the Clinical Center of EOHSI and was offered free of charge to the residents after their building was declared uninhabitable. Of the 27 adults and 6 children who were evaluated, one female elected not to complete the neurobehavioral testi ng and one male was exduded from neurobehavioral test analyses because of a preexisting neuropathy. Chinese was the first language for two additional residents; therefore, they did not complete the language-based performance tests (i.e., California Verbal Learning, Paired Associates, Vocabulary) and mood questionnaires [Symptom Checklist 90, Revised (SCL-90-R), Impact of Events Scale (IES)].
The ATSDR, the New Jersey Department of Health (NJDOH; Trenton, NJ), the EPA, the Hoboken Board of Health (Hoboken, NJ), and the Hudson Regional Health Commission (Harrison, NJ) investigated the site. Preliminary environmental and exposure results have been published (12), including air monitoring of the building conducted by both private consultants and the NJDOH, and spot urine samples obtained 27 December 1995 and analyzed for mercury by the NJDOH laboratory (13). Because of the high levels of mercury detected in the air and in residents' urine (up to 102 pg/l, normalized to a specific gravity of 1.024), the building was evacuated, all residents were relocated in January 1996, and the ATSDR referred the residents for medical examinations at the EOHSI.
Medical evaluation. These evaluations were performed in January-March 1996 (3-10 weeks postevacuation). Each subject was asked to review and sign an informed consent. The evaluation consisted of review of medical, occupational, and environmental history by a board-certified occupational physician and a targeted physical examination with special attention to blood pressure, respiratory, skin, oral cavities, and nervous systems. Blood chemistry panels, complete blood count, urinalysis, and urine creatinine were performed by a commercial clinical laboratory. On the day of the examination, a spot urine sample (urine2) was analyzed for mercury and creatinine by the NJDOH-Environmental and Chemical Laboratory Services. Specimens were collected in metal-free acid-washed plastic containers, refrigerated, and sent by courier to the NJDOH laboratory with field blanks (deionized water). Analysis was performed by cold vapor technique. Sample runs included calibration curves, spiked samples (recoveries >85%), and 10% duplicates. The interval between urinel and urine2 ranged from 5 to 11 weeks. All urine mercury levels were corrected for creatinine (C) to control for variable urine dilution.
Neuropsychological evaluation. Based on published studies of the neuropsychological effects of mercury exposure, tests reflective of the following functions were chosen: tremor, peripheral neuropathy, psychomotor coordination (speed), verbal learning and memory, basic skills or premorbid ability, and mood (4). To assess psychological distress, the IES, the SCL-90-R, and the Neurobehavioral Evaluation System 2 (NES2) mood scales were administered ( Statistical analyses. Because of the small sample size and the non-normality of the data sets, nonparametric data analytic methods were used. Wilcoxon rank sum tests were used to compare groups with high and low urine mercury level and Kendall Tau correlations were performed to assess the relationship between urine mercury and the dependent measures. Because of the small sample size and consequent lack of statistical power, significance levels of 0.10 or less are reported. For the purpose of statistical analysis, adult subjects with urinel above the median value of 19.4 pg/g creatinine (>19) were categorized as high exposure (n = 7 women, 3 men), whereas those <19 were classified as low exposure (n = 3 women, 6 men). Urinel was used because it reflected levels for subjects while exposures were ongoing. Therefore, the performance of 19 adult residents, classified as high or low exposure, were compared. Eight of the 27 subjects were not classified for the following reasons: one was excluded for neuropathy; one did not complete neurobehavioral tests; and six had no urinel data.

Results
Medical evaluation. Occupational, exposure, and medical histories were obtained from each adult subject. Of the 27 adults evaluated, there were 14 self-identified artists, 3 engineers, 3 computer specialists, 2 musicians, 2 salespeople, 2 construction contractors, and 1 financial trader. Seventeen considered themselves occupationally exposed to solvents including oilbased paints, paint thinners, and glues; 10 individuals did not have significant solvent exposure by history.
The medical history identified two subjects with a history of disease that included neurologic findings and predated their exposure to mercury, (i.e., connective tissue disorder and vascular disease). One of these refused neurobehavioral testing and results for the other were excluded from the statistical analyses. However, these two subjects were among those with the highest urine 1 mercury levels (i.e., 49.7 and 67.0 pg/g creatinine, respectively). Other pertinent results of the medical evaluation were as follows: history of multiple miscarriages (n = 1); difficulty conceiving (n = 1); pregnant at the time of evaluation (n = 1); nursing at the time of the evaluation (n = 1). During the interview by the occupational physician, all subjects denied current or past substance abuse or other exposure to mercury.
On physical examination, four subjects with abnormal skin conditions (one with psoriasis, three with eczema) were identified. One subject reported a hand tremor, which could not be seen on examination. One subject had a tongue tremor. Otherwise, physical findings were unremarkable.
Separate Wilcoxon rank sum analyses compared neurobehavioral performance and emotional symptoms of subjects high and low in urine mercury. The high-exposure group committed significantly more errors on the computerized hand-eye fine  (38) rotated to match a hole before being inserted and nondominant hand Peripheral neuropathy Vibration Threshold Using Vibratron lIa, an ascending protocol is used to measure Mean threshold score (39) sensitivity to vibration in first and fifth index finger on dominant and nondominant hands Psychomotor coordination Trail Making Test, Part A and B Timed paper and pencil test in which numbers are connected Time (sec) (40) in sequence as well as shifting between numbers and letters Symbol-Digit Substitution (NES2) Nine symbols and nine digits are paired in a key on the screen Average sec/digit (37) and the subject must press the digit on the keyboard corresponding to a test set of the nine symbols presented in scrambled order Simple Reaction Time (NES2) Test of concentration and visual reaction time where the Mean response latency (37) interstimulus interval is varied randomly to reduce effects of (msec Neurobehavioral, affect, and mood scores for all subjects were correlated with urinel. The correlation between urinel and errors on hand-eye coordination was significant (r = 0.37 p<0.03), whereas no other significant correlations were observed.
Psychological distress result. Although no statistically significant differences in measures of psychological distress were observed between those high and low in urine mercury, comparison of group means to normative standards available for the IES and the SCL-90-R was also conducted to determine the dinical significance of psychological distress for all subjects (n = 25) except those whose first language was Chinese (n = 2). For the IES, subjects had a level of total stress, intrusive and avoidant thoughts, and behaviors consistent with stress disorder patients seeking outpatient services (46). Most individuals reported trauma of leaving and losing their homes (n = 14). Two subjects cited medical concerns related to mercury poisoning, and two subjects were concerned about the stress of dealing with the financial, political, and legal problems. Seven subjects did not list a specific trauma.
For the SCL-90-R, mean T-scores for the group were within the clinically positive Environmental Health Perspectives * Volume 107, Number 5, May 1999 range (i.e., >63) for the global severity index and the obsessive-compulsive, depression, anxiety, hostility, and paranoid ideation scales. For an individual, a global severity index T-score >63 or two or more scale Tscores >63 is considered indicative of significant psychological distress (45). Twentyone of 25 subjects (84%) met this criterion.
Pediatric neurobehavioral evaluation. The six children were evaluated clinically by pediatricians and pediatric neurologists. Because of the small number of exposed children and the wide age range, statistical comparisons could not be made. However, relative to age-adjusted normative values, no clinically significant deficits were found for any of the children. None of the six children showed evidence of gross neuropathologic impairment. Subtle neurodevelopmental effects, however, can neither be identified nor ruled out in this evaluation.

Discussion
Residential exposure is a relatively rare event (47). The present study is unique in documenting moderately high residential exposures to mercury leading to urine mercury levels comparable to low-level occupational exposures (14,18). The group is unusual because more women than men were among the highest exposed, reflecting the fact that the female artists both lived and worked in the apartments. The neurobehavioral effects of both elemental and organic mercury are well established (48). Reduced performance on a task dependent on accurate fine motor coordination was observed among those subjects with higher urine mercury.
Although these results are consistent with findings from other investigations of occupational exposures [e.g., Ngim et al. (19), Netterstrom et al. (21), and Williamson et al. (49)], the present study cannot exclude factors other than mercury exposure to explain the results. First, several tests of motor function were administered with only one showing a significant difference and that difference was potentially confounded by gender. However, with a relatively small number, a difference remained after controlling for gender (p<O. 1 1). Moreover, on average, women perform better than men on tests of fine motor function (50). Therefore, the present finding of poorer performance among women in the sample is not consistent with the literature on other tests of fine motor function. In addition, an argument can be made that of the motor tests given, hand-eye coordination may be most sensitive to tremor. That is, hand-eye coordination requires fine movements with a joystick and detects errors on departures from a line on a video display. These task requirements may be more sensitive than the relatively gross requirements of placing pegs in holes [Grooved Pegboard (38)] or Finger Tapping (37). Moreover, fine subclinical tremor is not the same as peripheral neuropathy that was assessed with the vibratron. Despite these logical arguments, it is acknowledged that the present results may be a function of chance rather than of mercury exposure.
The present study also documented a significant level of psychological distress among subjects, 84% of whom reported a clinically diagnostic level of distress. Overall, the group reported levels of avoidant and intrusive symptoms similar to patients seeking services at a stress disorder clinic (46). Many of the symptoms reported (e.g., irritability, fatigue) may result from exposure to neurotoxicants such as mercury as well as from stress. Although causality cannot be inferred from the present study design, several factors suggest that the psychological symptoms were secondary to the discovery of contamination and subsequent evacuation rather than a direct neurotoxic effect of mercury. First, no significant differences in psychological measures were noted between the high and low urine mercury groups and no significant correlations were observed between urine mercury and measures of psychological distress on the SCL-90-R, Mood Scales, or IES. Second, when subjects were asked to record the traumatic event that they associated with their symptoms of avoidance or intrusion on the IES (46), the majority of subjects reported the trauma of being forced to leave their homes, workspaces, and possessions rather than mercury exposure per se. Thus, with few exceptions, the loss of homes or investments was coInsidered highly stressful.
A growing literature documents that both environmental and occupational exposures to chemicals have been associated with symptoms such as headaches, anxiety, depression, and fatigue (51-53). Spurgeon et al. (54) reviewed this literature and suggested a model that included not only the physical causes of these symptoms but also incorporated a sample of the psychological variables/stressors that contribute to symptom reports often attributed to a toxin. Health effects documented in the present study are examples of the complex interaction between chemical exposure and psychological stressors (e.g., loss of home) that occurred in response to that exposure.
The conversion of former industrial/ commercial facilities to artists' studios and residences has been part of urban revival in several large cities including New York City and Jersey City, New Jersey. In Hoboken, the artists' cooperative was led to believe that they were purchasing a former tool and die factory; information on former mercury vapor lamp production was withheld from them. Over a 1to 2-year period, the residents converted the building into about 16 large (approximately 4,000 ft2) apartments. They personially designed the layout and performed most of the carpentry and finishing work themselves. Unlike most apartment dwellers, these residents had huge emotional, time, and monetary investments in these apartments. Whereas their SpOuSeS went elsewhere to work, the artists both lived and worked full-time in the building.
Occupational health professionals are generally trained to evaluate health effects of exposure based on dose-response toxicology of a chemical. The present study demonstrates how the psychological stressors that accompany the exposuire may hav,e significant health effects of their owvn. Future studies to understand both the direct health risks of chemical and physical agents and indirect health risks dtie to psychological stressors are necessary to design better strategies for maximum reduction of persistent health effects after unintenided exposure. To offer pragmatic soltutions, these studies should incorporate not only toxic health risks from chemical expostire but the symptomatic psychological health consequences of regulatory and environmental interventionis.

Conclusion
In the summer of 1998, after 30 months of living in temporary EPA-subsidized housing and paying their mortgages on uninhabitable apartments, the Hoboken artists began receiving compensation from the federal government for their lost real estate. The artists continue to report significant psychosocial stress.
The impact of exposure to toxic chemicals extends beyond the direct organ toxicity and even beyond the future health risks that can only be estimated, and includes significant impacts on psychosocial wellbeing and quality of life.