Elemental Mercury Vapour Toxicity, Treatment, and Prognosis After Acute, Intensive Exposure in Chloralkali Plant Workers. Part I: History, Neuropsychological Findings and Chelator effects. Renata E.
1,2 Bluhm,
Robert G.
1,2 J. Frank Bonfiglio, Wood, 1,2 & Robert A. Branch1,2
3 Alastair J.J. Bobbitt,3 Larry W. Welch, 1,2 1 Andrew J. Heath Christopher Sarzen,
1Medicine, 2 Clinical Pharmacology and 3 Psychiatry Vanderbilt University School Departments of of Medicine, Nashville, TN 37232-6602, USA
Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the ’Symptom Check List 90-Revised’ (SCL-90R) and tests of visual-motor function such as ’Trailmaking Parts A and B’, ’Finger Tapping’, ’Stroop Colour Word Test’ and ’Grooved Pegboard.’ On day 85 ± 11 (mean±s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents. Rapidly resolving metal fume fever was the earliest manifestation of symptoms. CNS symptoms and abnormal performance on neuropsychological tests persisted over the prolonged period of follow-up. There were significant correlations between neuropsychological tests and indices of mercury exposure. Serial mercury in the blood and urine verified the long half-life and large volume of distribution of mercury. Chelation therapy with both drugs resulted in the mobilization of a small fraction of the total estimated body mercury. However, DMSA was able to increase the excretion of mercury to a greater extent than NAP. These observations demonstrate that acute exposure to elemental mercury and its vapour induces acute, inorganic mercury toxicity and causes
long-term, probably irreversible, neurological sequelae.
Introduction Elemental mercury vapour poisoning is an uncommon but serious occupational disease causing a prominent neurotoxic syndrome.’-’ The
widespread
use
of products
containing
mercury
and industrial processes that use mercury increases the number of workers at risk of mercury exposure. This paper describes a serious episode of mercury poisoning in a group of 53 men acutely
Correspondence:
exposed to elemental mercury
vapour while per-
forming routine maintenance work on the mercury cell of a chloralkali plant. Serial measurements of urinary excretion over a prolonged time allowed an estimation of the available pool of mercury initially absorbed. The slow urinary excretion of mercury also permitted a comparative short-term trial of N-acetyl-D, L-penicillamine (NAP) with a newer, chelating
Renata E. Bluhm
Downloaded from het.sagepub.com at Purdue University on June 19, 2015
202
agent, 2,3-dimercaptosuccinic acid (DMSA) in group of these
Vanderbilt University Hospital. Thus, there was a delay after the mercury exposure before patients were evaluated; 17 patients presented between day 19 and 36 after mercury exposure, and an additional nine thereafter. No information was available about the remaining 27 men who did not seek referral. Patients had a clinical examination, ECG, chest roentgenogram, pulmonary function tests, measurement of blood and urine mercury, arterial blood gases, serum sodium, potassium, chloride, blood urea nitrogen, serum creatinine, creatine phosphokinase and isoenzymes, complete blood count, thyroid function tests, urinalysis, urine creatinine, urine protein electrophoresis, and electromyograms with nerve conduction and velocity measure-
a
patients.
method A group of 53 men were exposed to elemental mercury vapour while performing planned reconstructive work on mercury cell lines at a chlorine manufacturing plant located in eastern Tennessee. The plant uses a mercury cathode as an electrolytic catalyst. The men had had expe-
rience with similar
repair work
on
other
occa-
sions ; however, previous repair work had been conducted on non-metal pipes and only cutting equipment had been used. On this occasion, oxyacetylene torches were needed to cut and ments. On a follow-up visit approximately 2 weeks repair metal pipes. Prior to the repair, the merthe patients’ physical exam was repeated cell were later, and the cury pipes power purged and the mercury in blood and urine was again mercury cell shut down. Despite this purging, many of the pipes still contained mercury, which measured. Since symptoms continued, they were remained in residual pools, particularly in de- treated for approximately 2 weeks between days 1 pendent areas of the pipes. The presence of 29 and 46 with either oral DMSA 30 mg kg -’ h NAP 8 or 250 mg every 6 h. Prolonged significant amounts of residual mercury in pipes every after purging is well recognized since the weight therapy was not offered as therapeutic benefit of mercury makes pooling inevitable. Workers was considered uncertain. Observation continued over several weeks. were exposed when welding equipment volatilized the mercury within the pipes being repaired Thereafter, 12 of the patients with persistently and replaced. The men described seeing the elevated urine mercury concentrations entered mercury boiling in the pipes and the release of into a comparative 4-d study of DMSA and NAP visible fumes of mercury during cutting. While which was approved by the institution’s ethical the men continued to repair the pipes, review committee. They were, thus, hospitalized vapourization and condensation of the mercury in the Clinical Research Center (CRC) between occurred. The men described mercury condensing on the ceiling and subsequently liquid mercury ’raining’ down over them, collecting in their clothes, shoes, on body surfaces and into a pool on the floor. Some of the men worked up to 16 h replacing pipes and removing the mercury into drains in the floor. Only a few men wore protective suits, rubber shoes or goggles and a few of them wore masks containing Merzorb® cartridges for limited times varying from 30 min to 4 h. There was no information quantifying mercury air levels during pipe cutting. Decontamination of the men at the job site was not undertaken. Thus, these men returned to their homes with clothes heavily contaminated with mercury, causing significant mercury contamination of floors, carpeting and washing machines as was documented by a later
investigation. Subsequently, a number of the men became ill and sought help from a physician, who attributed their symptoms to
virus. After several days of continuing symptoms, clinical reevaluation by another physician led to the identification of elevated urinary mercury levels. Twenty-six of the 53 men were referred to the a
73 and 116 d after the mercury exposure. The short-term study was designed to investigate the potential to mobilize mercury and the occurrence of drug-induced toxicity due to DMSA and NAP; it was not designed to yield therapeutic results, as chelation was administered late after exposure and only given for a short time. Blood and urine collections during the study were done by CRC unit nursing personnel. There were no
activity, dietary or smoking restrictions during this time. When possible, patients were randomized to receive either DMSA 30 mg kg -’ every 8 h or NAP 250 mg every 6, doses similar to those reported. 6-7 Six of the 12 patients were randomized, but the other six patients were not for the following reasons. During a previous administration of NAP, two patients developed a rash, the third patient felt that his symptoms worsened while on the drug, and the fourth patient refused further NAP treatment, since previously .he had no subjective improvement. The fifth :patient had haematuria of unknown aetiology, :possibly predating the mercury exposure, and ’NAP was felt to be relatively contraindicated. The sixth patient had experienced nausea, ’
1,2 Bluhm,
Robert G.
1,2 J. Frank Bonfiglio, Wood, 1,2 & Robert A. Branch1,2
3 Alastair J.J. Bobbitt,3 Larry W. Welch, 1,2 1 Andrew J. Heath Christopher Sarzen,
1Medicine, 2 Clinical Pharmacology and 3 Psychiatry Vanderbilt University School Departments of of Medicine, Nashville, TN 37232-6602, USA
Mercury poisoning occurred after the acute, prolonged exposure of 53 construction workers to elemental mercury. Of those exposed, 26 were evaluated by clinical examination and tests of neuropsychological function. Patients received treatment with chelation therapy in the first weeks after exposure. Eleven of the patients with the highest mercury levels were followed in detail over an extended period. Observations included the evaluation of subjective symptoms of distress, using the ’Symptom Check List 90-Revised’ (SCL-90R) and tests of visual-motor function such as ’Trailmaking Parts A and B’, ’Finger Tapping’, ’Stroop Colour Word Test’ and ’Grooved Pegboard.’ On day 85 ± 11 (mean±s.d.) after exposure, these 11 men again received either 2,3-dimercaptosuccinic acid (DMSA) or N-acetyl-D, L-penicillamine (NAP) in a short-term study designed to compare the potential to mobilize mercury and the incidence of drug-induced toxicity of these two chelating agents. Rapidly resolving metal fume fever was the earliest manifestation of symptoms. CNS symptoms and abnormal performance on neuropsychological tests persisted over the prolonged period of follow-up. There were significant correlations between neuropsychological tests and indices of mercury exposure. Serial mercury in the blood and urine verified the long half-life and large volume of distribution of mercury. Chelation therapy with both drugs resulted in the mobilization of a small fraction of the total estimated body mercury. However, DMSA was able to increase the excretion of mercury to a greater extent than NAP. These observations demonstrate that acute exposure to elemental mercury and its vapour induces acute, inorganic mercury toxicity and causes
long-term, probably irreversible, neurological sequelae.
Introduction Elemental mercury vapour poisoning is an uncommon but serious occupational disease causing a prominent neurotoxic syndrome.’-’ The
widespread
use
of products
containing
mercury
and industrial processes that use mercury increases the number of workers at risk of mercury exposure. This paper describes a serious episode of mercury poisoning in a group of 53 men acutely
Correspondence:
exposed to elemental mercury
vapour while per-
forming routine maintenance work on the mercury cell of a chloralkali plant. Serial measurements of urinary excretion over a prolonged time allowed an estimation of the available pool of mercury initially absorbed. The slow urinary excretion of mercury also permitted a comparative short-term trial of N-acetyl-D, L-penicillamine (NAP) with a newer, chelating
Renata E. Bluhm
Downloaded from het.sagepub.com at Purdue University on June 19, 2015
202
agent, 2,3-dimercaptosuccinic acid (DMSA) in group of these
Vanderbilt University Hospital. Thus, there was a delay after the mercury exposure before patients were evaluated; 17 patients presented between day 19 and 36 after mercury exposure, and an additional nine thereafter. No information was available about the remaining 27 men who did not seek referral. Patients had a clinical examination, ECG, chest roentgenogram, pulmonary function tests, measurement of blood and urine mercury, arterial blood gases, serum sodium, potassium, chloride, blood urea nitrogen, serum creatinine, creatine phosphokinase and isoenzymes, complete blood count, thyroid function tests, urinalysis, urine creatinine, urine protein electrophoresis, and electromyograms with nerve conduction and velocity measure-
a
patients.
method A group of 53 men were exposed to elemental mercury vapour while performing planned reconstructive work on mercury cell lines at a chlorine manufacturing plant located in eastern Tennessee. The plant uses a mercury cathode as an electrolytic catalyst. The men had had expe-
rience with similar
repair work
on
other
occa-
sions ; however, previous repair work had been conducted on non-metal pipes and only cutting equipment had been used. On this occasion, oxyacetylene torches were needed to cut and ments. On a follow-up visit approximately 2 weeks repair metal pipes. Prior to the repair, the merthe patients’ physical exam was repeated cell were later, and the cury pipes power purged and the mercury in blood and urine was again mercury cell shut down. Despite this purging, many of the pipes still contained mercury, which measured. Since symptoms continued, they were remained in residual pools, particularly in de- treated for approximately 2 weeks between days 1 pendent areas of the pipes. The presence of 29 and 46 with either oral DMSA 30 mg kg -’ h NAP 8 or 250 mg every 6 h. Prolonged significant amounts of residual mercury in pipes every after purging is well recognized since the weight therapy was not offered as therapeutic benefit of mercury makes pooling inevitable. Workers was considered uncertain. Observation continued over several weeks. were exposed when welding equipment volatilized the mercury within the pipes being repaired Thereafter, 12 of the patients with persistently and replaced. The men described seeing the elevated urine mercury concentrations entered mercury boiling in the pipes and the release of into a comparative 4-d study of DMSA and NAP visible fumes of mercury during cutting. While which was approved by the institution’s ethical the men continued to repair the pipes, review committee. They were, thus, hospitalized vapourization and condensation of the mercury in the Clinical Research Center (CRC) between occurred. The men described mercury condensing on the ceiling and subsequently liquid mercury ’raining’ down over them, collecting in their clothes, shoes, on body surfaces and into a pool on the floor. Some of the men worked up to 16 h replacing pipes and removing the mercury into drains in the floor. Only a few men wore protective suits, rubber shoes or goggles and a few of them wore masks containing Merzorb® cartridges for limited times varying from 30 min to 4 h. There was no information quantifying mercury air levels during pipe cutting. Decontamination of the men at the job site was not undertaken. Thus, these men returned to their homes with clothes heavily contaminated with mercury, causing significant mercury contamination of floors, carpeting and washing machines as was documented by a later
investigation. Subsequently, a number of the men became ill and sought help from a physician, who attributed their symptoms to
virus. After several days of continuing symptoms, clinical reevaluation by another physician led to the identification of elevated urinary mercury levels. Twenty-six of the 53 men were referred to the a
73 and 116 d after the mercury exposure. The short-term study was designed to investigate the potential to mobilize mercury and the occurrence of drug-induced toxicity due to DMSA and NAP; it was not designed to yield therapeutic results, as chelation was administered late after exposure and only given for a short time. Blood and urine collections during the study were done by CRC unit nursing personnel. There were no
activity, dietary or smoking restrictions during this time. When possible, patients were randomized to receive either DMSA 30 mg kg -’ every 8 h or NAP 250 mg every 6, doses similar to those reported. 6-7 Six of the 12 patients were randomized, but the other six patients were not for the following reasons. During a previous administration of NAP, two patients developed a rash, the third patient felt that his symptoms worsened while on the drug, and the fourth patient refused further NAP treatment, since previously .he had no subjective improvement. The fifth :patient had haematuria of unknown aetiology, :possibly predating the mercury exposure, and ’NAP was felt to be relatively contraindicated. The sixth patient had experienced nausea, ’
