JULY 2008 VOLUME 21, NUMBER 7 Copyright 2008 by the American Chemical Society
Guest Editorial Status of Toxicological Research in India Introduction It gives me great pleasure to congratulate the team of Chemical Research in Toxicology for completing 20 years in publishing cutting edge research in the area of toxicology and providing a common forum for numerous toxicologists across the globe. Furthermore, as a part of innovation and to generate awareness of toxicological issues (scientific and societal), the editorial series, “Toxicology: A Global Perspective” is highly applauded. I take this opportunity to highlight the issues and concerns in the area of environmental toxicology in modern day India. In addition, I utilize this platform to raise awareness and interest among fellow toxicologists in India and worldwide and highlight those issues and the remedial measures. India is a developing nation and presents demographic features quite similar to other developing countries. Emerging occupational and epidemiological health problems are major priorities that need to be tackled along with existing traditional public health problems like communicable diseases, malnutrition, poor environmental sanitation, and inadequate medical care. Although environmentalists and toxicologists in general, and the Government of India in particular, have expressed deep concern and have prioritized these issues, public awareness, toxicological databases, and suitable preventive measures are still lacking. One of the foremost requirements to improve the existing knowledge regarding the deleterious effects of toxicants and their preventive or therapeutic measures is to have the latest technologies, amenities, and resources for detecting toxic substances or their derivatives at nanogram (ng) levels. This step would aid to precisely quantify various toxicants and further facilitate research to develop (i) better therapeutic or preventive regimes and (ii) biomarkers to examine effects at the molecular level (1). In recent years, it has been realized that most of the diseases related to toxicants are incurable; therefore, the best course of action in dealing with them is prevention. The economic benefits and incurable nature of these diseases need to be highlighted, besides proposing investment in safety and remedial programs.
In the Indian context, one of the major obstacles to circumventing the above problem is literacy. Most of the population that suffers from these diseases are illiterate and are unaware of the hazards associated with the toxicants. Because of a gradual increase in the literacy rate in recent years, the general population in India is becoming aware of the toxicological consequences of substances around them. This editorial highlights the current issues related to the status of toxicology and efforts in the betterment of this field in India.
Current Status of Toxicology and Toxicologist in India In India, the underdevelopment of toxicology is primarily due to improper educational policies. The nation still lacks welldefined and elaborate postgraduate toxicology programs at the university level, and there is a dearth of human resources in this field. Most of the toxicologists (except forensic toxicologists) have only a bachelor’s degree in basic life sciences subjects. Consequently, they are unable to utilize the scientific approach in understanding and dealing with the environmental science or toxicology-related subject matters pertaining to chemicals and human health. Therefore, formulating a life sciences curriculum that comprises basic and applied toxicology and environmental sciences-related subject matter is desirable. The Department of Education has recently undertaken a few important steps in this direction. Young researchers in India understand the principles of toxicology only during their higher degree levels, that is, postgraduate or doctoral degree programs. Therefore, integration of their knowledge in understanding toxicology and environmental issues related to safe and effective preventive or therapeutic measures against xenobiotics, harmful chemicals, and environmental hazards usually takes a much longer time than their counterparts across the globe. Hence, one of the prime requirements to improve the current status of toxicology in India is enforcement of continuing educational programs related to occupational and environmental hazards (2). In recent decades, awareness in the Indian population of different forms of pollution that are a global threat has been
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growing. For instance, there is a greater awareness of background radiation from nuclear testing activities, indiscriminate use of pesticides and fossil fuels, and increased concentration of heavy metals in groundwater. According to a leading U.S. business magazine, small towns in India like Sukinda in Orissa and Vapi in Gujarat are among the top 10 most polluted cities globally. In Sukinda, large swaths of surface water and drinking water contain high covalent chromium levels potentially affecting 2.6 million people. Similarly, in Vapi. the chemical pollutants in the air and heavy metals from industrial estates have potentially affected over 70000 people residing in the township [(March 2, 2008) Headlines India.com, 6, 136]. Mercury in the groundwater in this area is reported to be 96 times higher than the World Health Organization (WHO) standards (3). Apart from this, recent reports by WHO suggest that certain parts of West Bengal have groundwater arsenic levels much higher than its permissible limit (10 µg/L), affecting nearly 50 million people in the state (4). Most of these environmental pollutants have resulted in serious health problems in these regions (5, 6). Heavy metals such as lead, arsenic, chromium, and mercury have a role in geochemical cycles (i.e., they occur as within “nature”). These metals are also mined and, depending on their processing, may be released in large concentrations into the environment. These heavy metals and other pollutants are reported to play a significant role in a variety of maladies, including cancer, lupus, immune diseases, allergies, and asthma. Other conditions that may occur include minamata, arsenicosis, and fluorosis disease, which are caused by mercury, arsenic, and fluoride intoxication, respectively. Although some serious efforts are currently underway by environmental legal regimes under the supervision of the Indian government (at both the state and the national levels) in circumventing the use and disposal of harmful chemicals and pollutants, enforcement of these laws at the local level is minimal. Various organizations have recently conducted studies in these polluted areas, proving the debilitating health impacts of toxic pollution. However, remediation actions remain piecemeal with no decisive plans to provide for effective health monitoring and abatement programmes. According to a recent report, the Indian Medical Association (IMA) reported that most of the drinking water supplies are contaminated due to the absence of proper disposing units for industrial effluents. This has resulted in very high incidences of respiratory diseases, chemical dermatitis, carcinoma, and skin, lung, and throat cancers. Women in these areas report exceedingly high incidences of spontaneous abortions, bleeding during pregnancy, abnormal fetuses, and infertility. Children’s ailments include respiratory and skin diseases and retarded growth. There has been no organized attempt thus far to set up centers dedicated to deal with poison cases in India. There are only two hospitals, The All India Institute of Medical Sciences (AIIMS) in New Delhi and Madras Medical Collge and General Hospital in Chennai, with special intensive care units for poisoning cases. Currently, such cases are treated in the emergency wards of most hospitals throughout the country. These facilities follow procedures adopted routinely to manage victims of any emergency, with little or no access to scientific backup and support of clinical and analytical toxicology.
Drug Development for Treating Cases of Poisoning One of the major areas of concern for toxicologists in India is a lack of baseline toxicology data for humans exposed to environmental pollutants/toxicants. The regulating agencies still
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depend upon the guidelines available from WHO, The National Institute of Environmental Health (NIEH), the United States, and other organizations, which are more pertinent to populations in western countries. Therefore, interpretation of exposure or human data between these two environmentally, geographically, and socioeconomically diverse populations gets difficult. Unless there is a coordinated effort between government and nongovernment agencies/research institutions in India, remedial measures do not seem near. In addition, another issue of great concern requiring immediate action is the lack of proper research facilities for toxicological testing and analysis of harmful toxicants. India lacks efforts in the development of drugs, particularly for treating cases of poisoning/toxicity. In spite of the increasing population that is exposed to arsenic and lead, it is highly regretted that there are no chelating agents or drugs available for treating these cases in India. In general, medical health practitioners have to depend on symptomatic treatments for treating such cases of poisoning. A number of cases related to chronic arsenicosis in India and Bangladesh currently have no available treatment as potent chelating drugs such as meso-2,3dimercaptosuccinic acid (DMSA) and 2,3-dimercaptopropane sulfonic acid (DMPS) proved unsuccessful in qualifying during the clinical trials. However, there are a few national research laboratories such as the Indian Institute of Toxicology Research (IITR) (Lucknow), Central Drug Research Institute (CDRI) (Lucknow), Defense Research and Development Establishment (DRDE) (Gwalior), and Food and Drug Toxicology Research Centre (FDTRC) at the National Institute of Nutrition (NIN) (Hyderabad) where efforts for generating a toxicology database and development of preventive and therapeutic measures for environmental pollutants, chemical warfare agents, and toxicants (6, 7) are under progress. The role of scientific organizations like the Society of Toxicology (STOX) (India), the Indian Pharmacological Society (IPS), and the Academy of Environmental Biology (AEB) is also worth mentioning in developing interest within upcoming toxicologists in the country. These societies organize annual conferences and meetings on current toxicological issues in India to create awareness among scientists and young researchers.
Future Direction and Conclusion The Indian scenario of toxicological data is in its development stage and comprises evaluation of safety measures against various toxicants. In recent years, a significant amount of work has been done to elucidate a profile of toxicants and to assess their possible modes of action. In this context, a new term, “toxicogenomics”, has been introduced, which is a newly born discipline of toxicology and comprises two major facets: one, how various genes in the genome respond to various toxicants and stressors, and two, how these toxicants modify the function and expression of specific genes in the genome (8). Various national and international government and private organizations have launched several programs on these gene-toxicant interactions. The Council of Scientific and Industrial Research (CSIR) (New Delhi, India) has launched a program on “toxicogenomics of genetic polymorphism in the Indian population” to industrial chemicals for development of biomarkers to provide better ventures and facilities to researchers to understand the toxicant-genome interactions. In addition, CSIR has recently launched a web-based program on single nucleotide polymorphism (SNP) with the aim to generate databases on the SNP in many genes in the Indian population. IITR is the coordinating laboratory and the Center for Cellular and Molecular Biology
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(CCMB) (Hyderabad), Institute of Genomics and Integrated Biology (IGIB) (Delhi), NEERI (National Environmental Engineering Research Institute) (Nagpur), and Indian Institute of Chemical Biology (IICB) (Kolkata) are the participating laboratories in this program. The major problem in toxicological research is cost effectiveness. Indian researchers spend their competence in finding solutions to those diseases that affect a lesser percentage of the population, while extensive and elaborate awareness programs for the diseases affecting the mass population need the utmost attention. Analyzing and screening the toxicological properties of a chemical are hugely expensive and utilize several years to complete. Hence, development of cost-effective methodologies is strongly required, which can adequately provide relevant information in this area. India also urgently needs a poison control program, which could provide the framework for both “prevention of” and “response to” poisoning, thereby contributing efficiently in chemical safety. These centers should have access to national and international databases to gather information on chemical and toxic poisoning. Clearly, if the poison control network in India is to meet the challenge, its aim should be earmarked, examined, and closely scrutinized. Special approaches are needed to address the problem of toxicology in India. These approaches should include assessment of chemical safety in the country (database), risk analysis and ranking of hazards, preparedness during emergencies, and compliance with regulatory requirements.
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Swaran J. S. Flora DiVision of Pharmacology and Toxicology, Defence Research and DeVelopment Establishment, Jhansi Road, Gwalior-474 002, India E-mail:
[email protected] or
[email protected] References (1) Agnihotram, R. V. (2005) An overview of occupational health research in India. Indian J. Occup. EnViron. Med. 9, 10–14. (2) Saiyed, H. N., and Tiwari, R. R. (2004) Occupational health research in India. Ind. Health 42, 141–148. (3) Brraune, B. M., and Malone, B. J. (2006) Mercury and selenium in livers of waterfowl harvested in Northern Canada. Arch. EnViron. Contam. Toxicol. 50, 284–289. (4) Mishra, D., Mehta, A., and Flora, S. J. S. (2008) Reversal of hepatic apoptosis with combined administration of DMSA and its analogues in guinea pigs: Role of glutathione and linked enzymes. Chem. Res. Toxicol. 21, 400–407. (5) Flora, S. J. S., Saxena, G., and Mehta, A. (2007) Reversal of leadinduced neuronal apoptosis by chelation treatment in rats: Role of ROS and intracellular Ca2+. J. Pharmacol. Exp. Ther. 322, 108–116. (6) Flora, S. J. S., Flora, G., and Saxena, G. (2006) Environmental occurrence, health effects and management of lead poisoning. In Lead: Chemistry, Analytical Aspects, EnVironmental Impacts and Health Effects (Cascas, S. B., and Sordo, J., Eds.) pp 158-228, Elsevier Publications, The Netherlands. (7) Vijayaraghavan, R., Kulkarni, A., Pant, S. C., Kumar, P., Rao, P. V., Gupta, N., Gautam, A., and Ganesan, K. (2005) Differential toxicity of sulfur mustard administered through percutaneous, subcutaneous, and oral routes. Toxicol. Appl. Pharmacol. 202, 180–188. (8) Patel, S., Parmar, D., Gupta, Y. K., and Singh, M. P. (2005) Contribution of genomics, proteomics, and single nucleotide polymorphism in toxicology research and Indian scenario. Indian J. Hum. Genet. 11, 61–75.
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