Study of the effects of hydrogen cyanide exposure in Cassava workers.

BACKGROUND: Hydrogen cyanide is the chemical responsible for tissue hypoxia. Chronic exposure to HCN may cause neurological, respiratory, cardiovascular and thyroid defects. Onset of symptoms depends on dose and duration of exposure. Large scale of Cassava processing could be disastrous due to discharge of hydrocyanic acid into the air. Cassava processing is the major industrial work in and around Salem. Hence the present study is taken to assess the effects of HCN exposure in Cassava workers.
MATERIALS AND METHODS: Thirty-nine workers from a Cassava processing unit at Salem and age-matched controls of the same economic status were taken up for this study. Clinical history was obtained with a questionnaire and their Blood sugar, lipid profile, serum total protein, urea, creatinine, AST, ALT and T(3), T(4), TSH were estimated using a fasting blood sample and AIP was calculated. Statistical analysis was done by student t test.
RESULTS: Our study reveals a significant increase in triglyceride in Cassava workers when compared to the control. Atherogenic index of plasma (AIP) is statistically highly significant. A significant decrease was seen in T(4.)
CONCLUSION: An increase in TGL and AIP shows a higher degree of cardiovascular risk. A decrease in T4 suggests an insufficient iodine uptake by thyroid gland. Hence a periodic medical evaluation should be done on such workers for their safety and to prevent the health hazard.

INTRODUCTION

Cassava (Manihot esculenta) is an important raw material for starch and sago industries. More than 600 units are engaged in sago industry in and around Salem city in Tamilnadu.

Cassava roots and leaves cannot be consumed as they contain two cyanogenic glycosides - linamarin and lotaustralin. They are decomposed by linamarase, a naturally occurring enzyme in Cassava, liberating hydrogen cyanide (HCN).[1] A safe processing method developed by Osppina[2] reported that 5/6 of cyanogenic glycosides are broken down by the linamarase and the resulting HCN escapes into the atmosphere making the edible flour safe for consumption. However, the processing may not ensure the complete removal of cyanide and the left out last traces are removed during digestion by detoxification. Industrial production of Cassava flour even at cottage level may generate HCN to have a severe environmental impact.[3] The processing of Cassava containing cyanogen glycoside leads to discharge of HCN to the air. The workers employed in these industries are under constant exposure to HCN via inhalation, skin contact and possibly also oral intake.[4] HCN is responsible for tissue hypoxia. Chronic exposure of HCN causing neurological, respiratory cardiovascular and thyroid defects were reported with workers in silver reclaiming process.

In human, HCN is detoxified with rhodanase forming a goiterogenic compound thiocyanate which is excreted in urine. This process requires sulfur donors such as dietary sulfur-containing amino acid.

The major reactions involved in detoxification of ingested cyanide includes[5]

Reaction with cysteine to form iminothiozilidine compound that is excreted through saliva and urine.

Minor amounts may be converted into formic acid and excreted in urine.

Cyanide may combine with hydroxyl cobalamine and excreted in urine and bile.

Hence the detoxification of HCN is influenced by the nutritional status, such as B vitamins like B12, folic acid and essential sulfur-containing amino acids provided by dietary good quality protein.[67] Systemic effects notably on the nervous system, digestive tract and thyroid have been reported after repeated occupational exposure to cyanide.[8-10] This compound is known to limit the ability of thyroid glands to store and process iodine. The goiterogenic effect of thiocyanate may also lead to endemic goiters. The effect of iodine deficiency can be devasting robbing the next generation of brain, power and productivity.[11] The impairment in thyroid function may also lead to alterations in other metabolic pathways especially lipids. Hence the present study is carried out to assess the effects of HCN exposure on lipid profile and thyroid functions in Cassava workers.

MATERIALS AND METHODS

Thirty-nine Cassava workers of 5 years exposure who are nonsmokers, nonalcoholic, free from diabetes mellitus, liver and kidney diseases and age-matched controls of the same economic status were taken up for this study. Their clinical history was obtained and the following parameters were estimated using a fasting blood sample. Blood sugar, lipid profile, serum total protein, urea, creatinine were estimated using Bayer diagnostic kits and T3, T4, TSH are assessed by ELISA method.

Statistical analysis

Datas were analysed using SPSS 11.0 version. Student ‘t’ test was used to find the significant difference between various parameters.

Ethical isssues: The purpose of the study was explained to all the participants and their consent was obtained. The requisite clearance of institutional human ethics committee was obtained.

RESULTS

Eighty percent of the workers complained of head ache/ dizziness/ vomiting/ eye irritation/ breathing difficulties and chest pain in various combinations as shown in the Figure 1. Twenty percent of the workers had no complaints.

Figure 1

Head ache + eye irritation 19 eye irritation+ dizziness 2 head ache + eye irritation+ dizziness+ vomiting + chest pain 2 vomiting 2 head ache + eye irritation + breathing difficulties 6 no symptoms 8

As shown in Table 1 the mean value of fasting blood sugar is comparable to the control group. Urea and creatinine are within the normal limits but a significant increase was seen in creatinine of Cassava workers compared to the control. A significant decrease was seen in total protein showing a nutritional deficiency. AST and ALT are within the normal limits but a marginal significance is seen in AST between the study groups.

Table 1

Basic biochemical parameters

The lipid profile of Cassava workers and the control groups is depicted in Table 2. The mean value of cholesterol is within the normal limits but a significant increase is seen in Cassava workers compared to the control group. A significant increase seen in HDL may not be a good indicator of CAD when compared with TGL/HDL ratio. A significant increase is seen in TGL/HDL ratio of Cassava workers compared to the control. LDL is within the normal limits. A significant increase is seen in VLDL. The atherogenic index of plasma is significantly increased in workers when compared to the control.

Table 2

Lipid profile

The thyroid profile shown in Table 3 reveals a significant decrease in T4 level in Cassava workers when compared to the control. There is no significant difference in T3 and TSH levels between the groups.

Table 3

Thyroid profile

DISCUSSION

Workers exposed to HCN for more than 5 years showed an increase in symptoms such as head ache, weakness, changes in taste and smell, irritation of throat, vomiting, lacrimation, abdominal colic, pericardial pain and nervous instability.[12] A retrospective study made in United States[4] among silver reclaiming workers reported that about 65% of the workers reported symptoms including eye irritation, loss of appetite, weight loss, nose block, fatigue, skin rashes, and shortness of breath, cough, sore throat, chest pain, heart palpitation and fainting. There was a significant positive trend between exposure levels of subjects and assessment of severity of poisoning.

AST is a marker enzyme for myocardial infarction.[3] A significantly elevated serum levels of AST and LDH found in women who were exposed to HCN for 8 hrs/day at work,[12-14] suggest the adverse effect of HCN in liver. However, the reports with animal experiments that revealed an increase in fasting blood sugar, change in myocardial morphology and behavioral changes during sub lethal dietary intake of cyanide, suggest an implication for human's consumption[1516] and Cassava exposure.

A marked increase in TGL is seen in Cassava workers. This is due to HCN which decreases glycolysis inhibiting TCA cycle and energy availability in the cells. Hence sugars are converted to TGL endogenously.[4] TGL may also increase in impaired thyroid function. The increase in VLDL reflects its functions in transporting the endogenously synthesized TGL.[17] It is shown that TGL/HDL is a more accurate predictor of heart disease than LDL/HDL ratio.[18] In a prospective study,[19] plasma triglycerides along with high LDL-C/HDL-C ratio[20] were of prognostic significance and are known to contribute CAD risk. Later TGL when used in a ratio with HDL-C was shown to be an excellent predictor of myocardial infarction.[21] Our study reveals an increase in atherogenic index of plasma (log TGL/HDL) which reflects the balance between the atherogenic and protective lipoproteins. AIP correlates with the size of pro- and antiatherogenic lipoprotein particles.[22] Clinical studies have shown that AIP predicts cardiovascular risk and it is an easily available cardiovascular risk marker and a useful measure of response to treatment.[23]

Decrease in T4 with normal T3 suggests, T4 is converting to T3 at high rate. This is typically found when the thyroid gland is unable to keep up T4 production to meet body's needs. The body can compensate by converting as much as T4 into T3.[24] Biochemical analysis by Banerjee et al,[10] revealed a higher average values for TSH and T3 but T4 was found to be normal. In another epidemiological study in which 36 Egyptian workers were exposed to cyanide for 5-15 years showed a gradual increase in the concentration of thiocyanate in urine.[1425] In an Indian study,[26] 35 workers who handled cyanide salts in a cable industry showed evidence of thyroid dysfunction and a positive correlation between serum levels of TSH and thiocyanate.

The present study shows that exposure of HCN during Cassava processing leads to an increase in CAD risk factors such as TGL/HDL ratio and AIP, and also an insufficient uptake of iodine by the thyroid gland. Hence occupational health interviews and physical examination at regular intervals during the employment should be mandatory. Medical screening tests should focus on identifying the adverse effects of HCN on the thyroid, liver, kidney, blood, CVS and CNS. Current health status should be compared with the baseline health status of the individual worker or with expected values of a suitable reference population.