British Journal of Industrial Medicine 1993;50:155-159 155 Systemic effects of inhalational methyl bromide poisoning: a study of nine cases occupationally exposed due to inadvertent spread during fumigation W N M Hustinx, R T H van de Laar, A C van Huffelen, J C Verwey, J Meulenbelt, T J F Savelkoul Abstract be absent. An on site investigation into the Systemic methyl bromide (CH3Br) poisoning circumstances leading to the accident showed with signs and symptoms of varying severity the presence of an empty and out of use drain- developed in nine greenhouse workers after age system that covered both sections of the acute inhalational exposure on two consecutive greenhouse. This was probably the most days. Measurements of CH,Br, carried out at important factor contributing to the rapid and the site within hours after the accident, suggest inadvertent spread of CH,Br. that exposure on the second day may have been in excess of 200 ppm (800 mg/m3) CH3Br. All workers were admitted for observation. Seven (British Journal of Industrial Medicine 1993;50:155-159) of them were discharged after an uneventful overnight observation and residual symptoms, if In the past methyl bromide (CH3Br) was mainly used any, subsided within three weeks of the as a fire extinguisher. In 1932 it was introduced as an accident. Two patients needed intensive care insecticide. Nowadays the compound is primarily for several weeks because of severe reactive used as a fumigant for the control of nematodes, myoclonus and tonic-clonic generalised con- fungi, and weeds in greenhouses, warehouses, and vulsions. These conditions were unresponsive mills. It is a colourless, non-inflammable, and highly to repeated doses of diazepam, clonazepam, volatile substance and exists in the gaseous phase at and diphenylhydantoin but could be suppres- normal pressures and temperatures. It has a density sed effectively by induction of a thiopental of more than three times that of air, which may coma that had to be continued for three weeks. explain its easy penetration in soil. Furthermore, it In some of the patients prior subchronic has poor warning properties because it is odourless exposure to CH3Br, as shown by their at concentrations of up to 100 times the Dutch occupational histories and high serum maximum allowable concentration (MAC) of5 ppm.' bromide (Brk) concentrations, is likely to have This may explain why CH3Br has so often caused been a factor contributing to the severity of serious and sometimes fatal poisoning.'2 Alexeeffand their symptoms. A direct association between Kilgore have extensively summarised and reviewed serum Bre concentrations and the severity of the reported poisoning incidents from CH3Br.5 They neurological symptoms, however, seemed to are not infrequently fatal. Legislative measures have considerably restricted the use of the compound in The Netherlands since 1981. The present report of occupational poisoning with underscores the Department of Intensive Care and Clinical CH3Br Toxicology need for continuous monitoring in and around W N M Hustinx, J Meulenbelt, T J F Savelkoul fumigation sites as an integral part of good fumiga- Department of Clinical Neurophysiology tion practice. It also shows the difficulties that may be A C van Huffelen encountered in the clinical management of the Department of Neurology, Utrecht State University Hospital neurological manifestations of serious systemic J C Verwey CH3Br poisoning. Generalised seizures after poison- National Poison Control Centre, National Institute ing with CH3Br may be resistant to treatment with of Public Health and Environmental Protection drugs like diazepam, clonazepam, and diphenyl- W N M Hustinx, R T H van de Laar, J Meulenbelt, J hydantoin. We describe treatment with thiopental as T F Savelkoul an effective alternative. 156 Hustinx, van de Laar, van Huffelen, Verwey, Meulenbelt, Savelkoul Materials and methods partition wall had its foundations 30-35 cm below The accident came to the attention of the National ground level. At a height ofaround 2 m above ground Poison Control Centre (NVIC) through requests for level several heating pipes passed the partition information about CH,Br poisoning by general through poorly sealed openings. The water drainage practitioners and physicians in neighbouring system, running at a depth of 100 cm and covering hospitals where two greenhouse workers, with both sections, had been closed before fumigation serious neurological signs of CH3Br poisoning, had started. After the accident, an empty and out of use been admitted. From interviews with their relatives set of drainage pipes was found at a depth of 120 cm, and the greenhouse owner it became clear that 80 cm above ground water level. These pipes also another seven people had probably been exposed to crossed the partition and covered the entire length of CH3Br as well. They were all traced within hours and the greenhouse. Both sections were heated at the time admitted to the intensive care and clinical toxicology of the accident. The recorded temperatures ranged department of Utrecht State University Hospital from 15'C in the fumigated section to 17°C near the for clinical observation, the department being an glass partition and 210C at the far end of the non- integrated unit with the NVIC. The two serious cases fumigated section. Soil temperature was <21'C in were also transferred to that same intensive care both sections. Of the non-fumigated section only the unit. All patients were examined by an internist part nearest to the partition wall was slightly and a neurologist. Further investigations included ventilated. The soil consisted of clay and was (1) blood sampling for routine haematology, bio- prepared for fumigation by rooting to 60 cm below chemical tests, and measurement of serum Br and ground level. The sections were fumigated separately blood CH3Br concentrations. This was repeated six with an interval of three weeks. The section where and 12 hours after admission and again six and 19 the exposure occurred had been fumigated three days later; (2) urinalysis, including a semi- weeks earlier. Fumigation was carried out from a quantitative check on the presence ofglucose, protein pressurised vapouriser, stationed outside the green- and traces of blood; (3) chest radiography; (4) blood house, by application of hot vapour through gas analysis; (5) electrocardiography (ECG); (6) daily perforated tubing under gas tight plastic sheeting. monitoring of seizure activity with 20-channel The sheeting was removed 10 days after fumigation. electroencephalography together with ECG and The dose used (200 g/m') was five times the movement recording, when indicated by abnormal legally allowed dose. During fumigation, a CH,Br findings on neurological examination. Measurement concentration of 25 ppm (100 mg/m') was measured ofblood CH3Br concentrations was performed by gas near the glass partition in the non-fumigated section. chromatographic analysis of air samples from head Away from the partition wall, concentrations rapidly space tubes (detection limit 0-005 ug/ml) and serum declined to below the detection limit. An employee bromide (Br-) measurements by induction coupled working near the partition was advised to keep away plasma mass spectrometry (detection limit 3 pg/l) from it. Unfortunately no repeat measurements were (Laboratory for Inorganic Chemistry, National done until after the accident. Five hours after all the Institute of Public Health and Environmental workers were forced to leave the greenhouse on the Protection). Data regarding the circumstances of the second day, CH,Br concentrations ranged from 200 accident were collected by the NVIC occupational ppm near the partition-wall to 150 ppm at the far end hygienist through interviews with patients, the of the non-fumigated section. No CH,Br was greenhouse owner, and employees of the firm that detectable at the outside perimeter ofthe greenhouse. contracted the fumigation job. He also visited the site Sixteen days after the accident the CH,Br concentra- had fallen to below the ofthe accident. Repeated CH3Br measurements were tion in the fumigated section carried out for 19 days after the accident with a Dutch MAC of 5 ppm and it took 20 days for CH3Br Drager gas detector (tubes 3/a and 5/a with detection to become undetectable. In the non-fumigated had to MAC limits of 3 ppm and 5 ppm respectively). section CH,Br concentrations dropped Measurements were done in ambient air at 10-100 and zero after five and 15 days respectively. cm above ground level. Whenever it was considered relevant in describing the sequelae of the accident, PATIENTS workers patients are identified in the text by numbers in The accident involved nine greenhouse (two parentheses. women, seven men; age 21-40 years). Three weeks before the accident five of them (2, 3, 5, 8, 9), Results including the two patients (8 and 9) with serious CIRCUMSTANCES OF THE ACCIDENT neurological signs ofpoisoning, had been working in The accident occurred in a greenhouse consisting of the section of the greenhouse later to be fumigated, two sections with a surface area of almost 8500 m' while fumigation was in process in the other section. each, separated by a glass partition wall. A door in Already at that time, two workers (3 and 6) had this wall was sealed with weather stripping. The experienced symptoms (nausea, vomiting, and dizzi- Systemic effects ofmethyl bromide poisoning 157 ness) that might retrospectively be attributable to microorganisms considered to be contaminants. For CH3Br poisoning. Another worker (9) had been some time both patients had to be ventilated with involved in a car crash two weeks before the poison- 04-0 5 fractional inspired oxygen but application of ing accident. The man had a complete amnesia for the positive end expiratory pressure was never con- car accident despite no evidence of skull or brain sidered necessary. It took three weeks before damage. His relatives reported a striking absent thiopental administration could be withdrawn after mindedness that had become apparent already before electroencephalograms had shown epileptiform pat- the accident.