revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY
2. HEALTH EFFECTS
of hair revealed that after a brief lag time, mercury content rose rapidly to almost 1,100 ppm (normal level,
50 ppm), and then slowly declined with a half-life of 74.6 days. These results
support the occurrence of one or several episodes of exposure, and are consistent with laboratory notebook
accounts of a single accidental exposure. Testing of family members, laboratory coworkers, and laboratory
surfaces failed to reveal any unsuspected mercury spills or other cases of toxic blood or urinary mercury
levels. Permeation tests subsequently performed on disposable latex gloves similar to those the patient had
worn at the time of the lone exposure revealed that dimethylmercury penetrates such gloves rapidly and
completely, with penetration occurring in 15 seconds or less and perhaps instantly. Polyvinyl chloride
gloves were equally permeable to dimethylmercury. Five days prior to hospital admission, the patient
developed a progressive deterioration in balance, gait, and speech. During the previous 2 months, she had
experienced brief episodes (spaced weeks apart) of nausea, diarrhea, and abdominal discomfort, and had
lost 6.8 kg (15 lb). Medical examination revealed moderate upper-extremity dysmetria, dystaxic
handwriting, a widely based gait, and “mild scanning speech.” Routine laboratory test results were normal.
Computed tomography (CT) and magnetic resonance imaging (MRI) of the head were normal except for the
incidental finding of a probable meningioma, 1 cm in diameter. The cerebrospinal fluid was clear, with a
protein concentration of 42 mg/dL and no cells. A preliminary laboratory report indicated that the wholeblood
mercury concentration was more than 1,000 µg/L (normal range, 1–8 µg/L; toxic level, >200 µg/L).
Chelation therapy with oral succimer (10 mg/kg orally every 8 hours) was begun on day 168 after exposure.
Whole blood concentrations rose to 4,000 µg/L after one day of chelation, and urinary mercury levels were
234 µg/L (normal range, 1–5 µg/L; toxic level, >50 µg/L). Despite the initial success of chelation therapy,
administration of vitamin E, and a blood exchange transfusion, at 176 days postexposure, the patient
became comatose. Further aggressive general support and chelation therapy failed, life support ws removed
(following the patient’s advance directive), and the patient died 298 days postexposure. Autopsy results
revealed diffusely thin cortex of the cerebral hemispheres (to 3 mm), and extensive gliosis of the visual
cortex around the calcarine fissure and the superior surface of the superior temporal gyri. The cerebellum
showed diffuse atrophy of both vermal and hemispheric folia. Microscope evaluation revealed extensive
neuronal loss and gliosis bilaterally within the primary visual and auditory cortices, with milder loss of
neurons and gliosis in the motor and sensory cortices. There was widespread loss of cerebellar granular-cell
neurons, Purkinje cells, and basket-cell neurons, with evidence of loss of parallel fibers in the molecular
layer. Borgmann’s gliosis was well developed and widespread.
The highest NOAEL values and all reliable LOAEL values for neurological effects in each species and
duration category are recorded in Table 2-1 and plotted in Figure 2-1.
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