RESEARCH

Treatment Techniques & Results

LEAD TOXICITY: TREATMENT AND PREVENTION

Dr. B. Dinesh and Dr. Kamala Krishnaswamy

Lead is a major environmental pollutant and its toxicity continues to be a major public health problem in many segments of the population. There is a growing consensus that lead causes toxic injury to humans at a level of exposure that was considered to be safe only a decade ago. The major symptoms of lead poisoning are not observed at prescribed safety limits of blood levels (10 m g/dl). The chronic exposure to lead even at low levels can result in slow progressive and most of the time irreversible damage to hematopoietic, nervous and renal systems (1-3).

In recent years, research efforts are directed towards quantification of the impact of lead exposure on human health, particularly from environment. The diagnosis based on the blood lead levels does not always give an accurate estimate of the total body burden of lead, duration of exposure and extent of sub-clinical toxicity which is more common than acute lead toxicity. Therefore, it is important to detect sub-cellular damage using reliable sensitive biochemical markers for early organ damage. The decreased erythrocytic delta amino levulinic acid dehydratase activity (ALAD) and increased urinary excretion of renal tubular lysosomal enzyme N-acetyl-B-D-glucosaminidase (NAG) are reported to be sensitive indicators of early hematopoietic and renal toxicity respectively (4-6).

The treatment of lead poisoning especially at sub-clinical level is equally important. The potent chelators like ethylene diamine tetraacetic acid (EDTA) and Dimercaprol are good for treating acute poisoning. However disadvantages of using the above chelators include possible renal toxicity, pain at injection site and low absorption. Recently, the use of oral Dimercaprol succinic acid (DMSA) has been reported to be effective in treatment of children having blood lead levels above 20 m g/dl. However it is expensive and the product is not marketed in India. Since a decade, there are sufficient reports on the role of dietary factors in absorption/prevention of lead toxicity. More recently, the role of vitamins especially that of thiamine in treating/preventing chronic lead toxicity in animals is gaining wide attention (7).

In view of the above and the scanty availability of information on the interrelationship between lead toxicity and nutritional status in India, several investigations were carried out to assess the extent of lead toxicity in various group of population exposed occupationally as well as in children.

Investigations carried out during the1980’s in lead mining areas of Andhra Pradesh (South India) indicated the prevalence of neurological disease in cattle due to lead poisoning. The study also cautioned the impending danger which might arise due to consumption of milk of affected cattle or the consumption of crops raised in the affected areas by humans (8).

In the employees working in various automobile garages, the blood lead levels were elevated (40.9 + 29 m g/dl), coupled with 4-7 fold elevated enzymuria (enzyme in urine) as compared to the normal subjects (23.3 + 3.1 m g/dl). In 36% of the garage employees, the clinical symptoms such as gum-line, tremors, sensory and motor disturbances were also noticed.

However, there was no significant difference in parameters such as hemoglobin levels (Hb), and serum albumin, as compared to normals. Similarly in another occupational group (monocastors) who were constantly exposed to lead fumes during the preparation of lead press metals, the blood lead levels were found to be two fold higher (41.9 + 7.0 m g/dl), coupled with 40-60% inhibition in basal ALAD activity and 4-8 fold elevated excretion of urinary enzyme NAG compared to normals (10). On further analysis of data, the blood lead levels correlated significantly with biochemical markers viz. ALAD (r=0.67) and NAG (r=0.54). However, the blood lead levels did not correlate with the duration of the exposure. The inhibition of ALAD activity, elevated enzymuria and increased blood lead level were correlated significantly with each other indicating the possibilities of assessing sub-clinical toxicity to hematopoietic and renal system using the above markers.

In addition, three categories of children who were exposed to lead directly or through their nature of occupation were screened. The mean blood lead levels were found higher in all the three groups. It is alarming to note that more than 35% children working in petrol bunks have very high blood lead levels above 35 m g/dl; 17% per cent of the 55 children engaged in bangle making industry had mean blood lead levels more than 30 m g/dl; and in pica eating children 47% had blood lead levels around 29 m g/dl.

In some parts of western India, where there were reports on premature death of cattle population due to lead toxicity, children were screened to assess the extent of lead toxicity. It was found that children who stay within the vicinity of 0-5 km of an industry engaged in preparation of packing material, the mean lead levels were one and half times higher (35.2 m g/dl as compared to those children residing further away (23 to 28 m g/dl). These children also suffered from clinical symptoms like loss of appetite, gum-line and low hemoglobin levels (12).

Besides identifying the magnitude of the problem of lead toxicity, an attempt was also made to evaluate beneficial effects of thiamin in animal and human. A pilot study in mono-casters suggests that the daily administration of thiamin (50- 100 mg) not only restored 30-50% of the basal ALAD activity and reversed the urinary NAG activity, but also reduced blood lead levels by 25-30% in a span of 9-10 months (13). Experimental studies also showed that thiamin administration helped in preventing the accumulation of lead in tissues and in leaching out stored lead gradually. The mechanism of such action seems to be by chelation of lead by thiamine, as revealed by NMR spectroscopy. Thus, a simple vitamin supplement such as thiamin, which is non-toxic and economically viable, can be recommended for prevention/treatment of the toxic effects of lead.

It is important to realize that lead has no physiological benefit and its toxicity is preventable. The only primary prevention is limiting exposure to lead in the environment. In developing countries such as India, it may be difficult to prevent the potential sources of exposures, namely gasoline additives, lead in paints, water pipes and batteries. The intervention requires a specific approach to the source. The Government should adopt and enforce regulation to control industrial air, water and other emissions. There should be a ban in the employment of children in cottage industries such as bangle making sectors and in petrol and auto garages. Measurement of occupational exposures, and air level monitoring coupled with blood lead screening in workers should be made mandatory. Use of safer technologies, protective clothing and filters can bring down the exposure. Household traditional remedies need to be checked for lead content. A fresh look at lead content in drinking water and in building materials is the need of hour. Above all, information needs to be generated on lead burden in different segments of the population for controlling exposure.

References

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the heme pathway. Proc. Natl. Acad. Sci. 1972, 69: 2381-2385.

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Contam Toxicol 1980, 25: 142-45.

9. Kumar BD, Krishnaswamy K. Detection of occupational lead

nephropathy using early renal markers. Clin Toxicol 1995, 33: 331-335.

10. Kumar BD, Krishnaswamy, K. Detection of sub-clinical lead toxicity in monocasters.

Bull Environ Contam Toxicol 1995, 54: 863-869.

11. National Institute of Nutrition, Hyderabad, Ann Rep 1992-93, 97-98.

12. National Institute of Nutrition, Hyderabad, Ann Rep 1995-96, 43-44.

13. Kumar BD, Khan N~I, Krishnaswamy K. Therapeutic potential of thiamin in lead

toxicity. A clinical study. Indian J Pharmacol 1994, 26: 227-281.

14. Krishnaswamy K, Kumar BD. Lead toxicity. Indian Pediatric 1998, 35: 209-214.

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