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An outbreak of tricresyl phosphate poisoning in Calcutta, India
Fd Chem. Toxic. Vol. 28, No. 4, pp. 303-304, 1990
Pergamon Press plc. Printed in Great Britain
LETTER TO THE EDITOR
AN OUTBREAK OF TRICRESYL PHOSPHATE POISONING IN CALCUTTA, I N D I A Sir,--Tricresyi phosphate (TCP) is an odourless, colourless and stable industrial chemical. It is used in lacquers and varnishes, in cellulose acetate, nitrocellulose and polyvinylchloride sheets as a plasticizer, and also in hydraulic fluid, which is used in ships and nuclear powered submarines. TCP has been shown to cause polyneuritis in animals and humans, eventually leading to paralysis of the hands and feet (Senanayke and Jeyarathan, 1981; Taylor, 1967). Although not every step in its development is identified, the syndrome is understood to be initiated by irreversible inhibition and ageing of neuropathy target esterase (NTE) (Johnson, 1982). It appears that the o-isomer of TCP is more toxic than the m- or p-isomers (Johnson, 1975). Outbreaks of TCP poisoning have occurred in the past in the USA, Morocco, India, Durban and Sri Lanka. During the past decade, two major epidemics occurred in the state of West Bengal, India. However, no scientific report regarding these outbreaks is available. In July 1988 an outbreak, caused by the consumption of adulterated rapeseed oil, occurred in the Behala area on the south-west outskirts of Calcutta, India. Though there were no deaths, about 600 victims reported to Vidya Sagar Hospital, Calcutta, of which 343 were admitted. Of these patients, 203 were males and 140 females. The School of Tropical Medicine in Calcutta was the first to identify the causal agent as TCP. During this period several rapeseed oil samples from the Behala area were analysed using the modified method of Collins (1945). Six of these samples were found to be contaminated with TCP to the extent of 22-57%. Detailed examination of 135 victims belonging to 65 families (82 males and 53 females from different age groups), revealed that the average age of the victims was 28.25 + 1.34 yr (mean + SE). The total oil consumption, as assessed by the method of Gopalan et al. (1977), was calculated to be 94.89 + 16.46 g (mean + SE) per consumption unit over a period of 2.44 + 0.44 days (mean + SE). The majority of the patients had a history of gastric upset at the onset of poisoning followed by numbness, tingling and weakness of the lower limbs after 5-7 days of consumption of the contaminated oil. The weakness in the lower limbs increased in the second week and was followed by involvement of the upper limbs. Foot drop was encountered in nearly all the severe cases, which indicated weakness of the proximal muscle. Upper limbs were affected in more than half of the patients admitted, the salient feature being wrist drop. On examination, ankle jerk was absent and knee reflexes were poor. The patients were treated for their symptoms and given supplements of vitamin B complex. The follow-up studies of these patients during April 1989 revealed that there were still about 500 cases receiving treatment in two rehabilitation camps. Many patients who had suffered from foot drop were still not completely mobile, while in others the gait was jerky. Muscle tone and power were below normal in most cases. A weak hand grip and early fatigue was a frequent complaint. It is apparent, therefore, that even 8 months after the outbreak, recovery in these patients was extremely poor and residual neurological loss persisted. Though the question of complete recovery in some of the severe cases remains doubtful, regular physiotherapy may improve the prospects of rehabilitation. Morgan and Penovich (1978) reported little long-term improvement in a 47-yr follow-up study. That inhibition of NTE is very rapid and that spinal axons once degenerated at their distal ends fail to regenerate is consistent with poor prognosis, although some improvement might be expected in mild cases principally involving some peripheral nerves. Cases of TCP poisoning continue to occur from time to time. The number of cases may not always be large but many victims remain disabled and crippled for the rest of their lives. No specific line of treatment is known at present, and further research to remedy this situation is desirable. Acknowledgements--The authors are grateful to Dr P. K. Ray, Director, ITRC, for his keen interest in this study.
Thanks are due to K. G. Thomas and U. Prasad for typographical assistance.
References Collins E. (1945) Reaction of diazotised p-nitraniline with phenols: detection of tricresyl phosphate in edible oil. Analyst, Lond. 70, 326. Gopalan C., Ramasastri B. V. and Balasubramanium S. C. (1977) Nutritive value of Indian foods. National Institute o f Nutrition Bulletin, ICMR, Hyderabad, India. p. 10.
303
304
Letter to the Editor
Johnson M. K. (1975) The delayed neuropathy caused by some organophosphorus esters: mechanism and challenge. CRC Crit. Rev. Toxicol. 3, 289. Johnson M. K. (1982) The target for initiation of delayed neurotoxicity by organophosphorus esters: biochemical studies and toxicological applications. Rev. Biochem. Toxic. 4, 141. Morgan J. P. and Penovich P. (1978) Jamaica Ginger paralysis---47-year follow-up. Archs Neurol. 35, 530. Senanayke N. and Jeyarathan J. (1981) Toxic polyneuropathy due to gingili oil contaminated with tri-cresyl phosphate affecting adolescent girls in Sri Lanka. Lancet i, 88. Taylor J. D. (1967) A neurotoxic syndrome produced in cats by a cyclic phosphate metabolite of tri-o-cresyl phosphate. Toxic. appl. Pharmac. 11, 538. A. K. Srivastava, Mukul Das and S. K. Khanna* Dyes & Food Adulterant Toxicology Laboratory, Industrial Toxicology Research Centre, Post Box 80, Mahatma Gandhi Marg, Lucknow-226 001, India
*To whom all correspondence should be addressed.
Pergamon Press plc. Printed in Great Britain
LETTER TO THE EDITOR
AN OUTBREAK OF TRICRESYL PHOSPHATE POISONING IN CALCUTTA, I N D I A Sir,--Tricresyi phosphate (TCP) is an odourless, colourless and stable industrial chemical. It is used in lacquers and varnishes, in cellulose acetate, nitrocellulose and polyvinylchloride sheets as a plasticizer, and also in hydraulic fluid, which is used in ships and nuclear powered submarines. TCP has been shown to cause polyneuritis in animals and humans, eventually leading to paralysis of the hands and feet (Senanayke and Jeyarathan, 1981; Taylor, 1967). Although not every step in its development is identified, the syndrome is understood to be initiated by irreversible inhibition and ageing of neuropathy target esterase (NTE) (Johnson, 1982). It appears that the o-isomer of TCP is more toxic than the m- or p-isomers (Johnson, 1975). Outbreaks of TCP poisoning have occurred in the past in the USA, Morocco, India, Durban and Sri Lanka. During the past decade, two major epidemics occurred in the state of West Bengal, India. However, no scientific report regarding these outbreaks is available. In July 1988 an outbreak, caused by the consumption of adulterated rapeseed oil, occurred in the Behala area on the south-west outskirts of Calcutta, India. Though there were no deaths, about 600 victims reported to Vidya Sagar Hospital, Calcutta, of which 343 were admitted. Of these patients, 203 were males and 140 females. The School of Tropical Medicine in Calcutta was the first to identify the causal agent as TCP. During this period several rapeseed oil samples from the Behala area were analysed using the modified method of Collins (1945). Six of these samples were found to be contaminated with TCP to the extent of 22-57%. Detailed examination of 135 victims belonging to 65 families (82 males and 53 females from different age groups), revealed that the average age of the victims was 28.25 + 1.34 yr (mean + SE). The total oil consumption, as assessed by the method of Gopalan et al. (1977), was calculated to be 94.89 + 16.46 g (mean + SE) per consumption unit over a period of 2.44 + 0.44 days (mean + SE). The majority of the patients had a history of gastric upset at the onset of poisoning followed by numbness, tingling and weakness of the lower limbs after 5-7 days of consumption of the contaminated oil. The weakness in the lower limbs increased in the second week and was followed by involvement of the upper limbs. Foot drop was encountered in nearly all the severe cases, which indicated weakness of the proximal muscle. Upper limbs were affected in more than half of the patients admitted, the salient feature being wrist drop. On examination, ankle jerk was absent and knee reflexes were poor. The patients were treated for their symptoms and given supplements of vitamin B complex. The follow-up studies of these patients during April 1989 revealed that there were still about 500 cases receiving treatment in two rehabilitation camps. Many patients who had suffered from foot drop were still not completely mobile, while in others the gait was jerky. Muscle tone and power were below normal in most cases. A weak hand grip and early fatigue was a frequent complaint. It is apparent, therefore, that even 8 months after the outbreak, recovery in these patients was extremely poor and residual neurological loss persisted. Though the question of complete recovery in some of the severe cases remains doubtful, regular physiotherapy may improve the prospects of rehabilitation. Morgan and Penovich (1978) reported little long-term improvement in a 47-yr follow-up study. That inhibition of NTE is very rapid and that spinal axons once degenerated at their distal ends fail to regenerate is consistent with poor prognosis, although some improvement might be expected in mild cases principally involving some peripheral nerves. Cases of TCP poisoning continue to occur from time to time. The number of cases may not always be large but many victims remain disabled and crippled for the rest of their lives. No specific line of treatment is known at present, and further research to remedy this situation is desirable. Acknowledgements--The authors are grateful to Dr P. K. Ray, Director, ITRC, for his keen interest in this study.
Thanks are due to K. G. Thomas and U. Prasad for typographical assistance.
References Collins E. (1945) Reaction of diazotised p-nitraniline with phenols: detection of tricresyl phosphate in edible oil. Analyst, Lond. 70, 326. Gopalan C., Ramasastri B. V. and Balasubramanium S. C. (1977) Nutritive value of Indian foods. National Institute o f Nutrition Bulletin, ICMR, Hyderabad, India. p. 10.
303
304
Letter to the Editor
Johnson M. K. (1975) The delayed neuropathy caused by some organophosphorus esters: mechanism and challenge. CRC Crit. Rev. Toxicol. 3, 289. Johnson M. K. (1982) The target for initiation of delayed neurotoxicity by organophosphorus esters: biochemical studies and toxicological applications. Rev. Biochem. Toxic. 4, 141. Morgan J. P. and Penovich P. (1978) Jamaica Ginger paralysis---47-year follow-up. Archs Neurol. 35, 530. Senanayke N. and Jeyarathan J. (1981) Toxic polyneuropathy due to gingili oil contaminated with tri-cresyl phosphate affecting adolescent girls in Sri Lanka. Lancet i, 88. Taylor J. D. (1967) A neurotoxic syndrome produced in cats by a cyclic phosphate metabolite of tri-o-cresyl phosphate. Toxic. appl. Pharmac. 11, 538. A. K. Srivastava, Mukul Das and S. K. Khanna* Dyes & Food Adulterant Toxicology Laboratory, Industrial Toxicology Research Centre, Post Box 80, Mahatma Gandhi Marg, Lucknow-226 001, India
*To whom all correspondence should be addressed.