1. Toxicological Studies on Pesticides in India (By: Dr. Aruna Dewan)

2. Indoor air pollutants associated with solid fuel use (By: K Balakrishnan, S Sankar, R Padmavathi, S Mehta, KR Smith)

3. Heavy Metals Exposure as Potential Risk Factors for Cancer Development and Organ Damage (By: Mohmmad Athar, MN. Sarwar Alam and Gayatri Bhasin

4. Polycyclic Aromatic Hydrocarbons in Environment and Associated Challenges (By: Dr. (Mrs.) Neeta Thacker)

5. Mechanism Based on Biomarker for Toxicity Assessment of Chemicals with particular reference to metals and pesticide (By: Prahlad K Seth)

6. The bioavailability of polycyclic aromatic hydrocarbons from polluted soils (By: P.S. Chauhan)

7. Structure-Activity Relationships in Envionmental Toxicology (By: Dr. H. N. Saiyed)

8. Mechanisms of Ionising Radiation and Chemicals in Carcinogenesis: Comparative Studies (By: S.C. Sehgal)

9. Environmental geology related to the risks of chemicals (By: Tarala Nandedkar)

10. Chemical Policy and standard setting by the Europian Union (By: Y.K. Gupta)
     

Toxicological Studies on Pesticides in India
Dr. Aruna Dewan
 DD SG, NIOH, Ahmedabad, India
 

Pesticides are extensively used in India for agriculture and public health programmes. India started pesticide production in the year 1952. In 1958, India was producing over 5000 metric tonnes of pesticides. At present , India’s pesticide industry is fourth largest in the world and production has increased to approximately 85,000 metric tonnes with 165 pesticides registered for use in the country. The consumption of pesticides in India is still very low, about 0.5 kg/ha of pesticides but there has been widespread contamination of food commodities with pesticide residues, mainly due to non-judicious use of pesticides. Literature survey shows that most of studies on pesticides done in India reflect presence of pesticides residues in sizeable amounts in food and agricultural commodities. Animal toxicity studies carried out in the country range from neurotoxicity, reproductive toxicity, genotoxicity, immunosupression and carcinogenicity. However, data on human health effects is mainly related to acute poisoning cases reported from different parts of India. Studies on chronic health effects of pesticide exposures are relatively few. Some of the studies have been carried out in occupationally exposed subjects such as agricultural workers, malaria spraymen, pesticide manufacturers and formulators. Exposure to organophosphates and carbamates (Methomyl) was found to cause cardiac toxicity in exposed persons. Some recent studies show a possible link between pesticide exposures and health effects such as intrauterine growth retardation, breast cancer, endocrine disruption etc. Available data points that pesticide pollution does exist in the country and is a cause for concern. This paper will focus on health effect studies on pesticides in India highlighting the future needs.

 

INDOOR AIR POLLUTANTS ASSOCIATED WITH SOLID FUEL USE –RESULTS OF EXPOSURE ASSESSMENT AND MODELING EXERCISES IN ANDHRA PRADESH INDIA

K Balakrishnan1 *, S Sankar1, R Padmavathi1, S Mehta2, KR Smith2

1Environmental Health Engineering, Sri Ramachandra Medical College & Research Institute, (Deemed University), Chennai, India
2Environmental Health Sciences, University of California, Berkeley, CA, USA
 

Heavy Metals Exposure as Potential Risk Factors for Cancer Development and Organ Damage

Mohmmad Athar, MN. Sarwar Alam and Gayatri Bhasin

Department of Medical Elementology and Toxicology,
Hamdard University, New Delhi-110 062
 

Heavy metals contamination particularly in water bodies and food chain is a major cause of heavy metals exposure to humans in India other than related to their occupational exposure. In various states particularly in Assam and Orrisa, high levels of iron have been detected in ground water and in other water bodies, which provide a major source of drinking water. Besides, soaps and detergents are ultimately discharged directly into water bodies, which are rich in pyrophosphates and their mimics such as nitrilotriacetate (NTA). These agents form a variety of metal complexes with heavy metal ions including iron. These metal complexes are often potentially toxic and carcinogenic. Therefore, we investigated the effects of Fe-NTA on renal and hepatic damage leading to carcinogenesis. In addition we have also investigated the chemopreventive effects of distary agents on the abrogation of their toxic manifestations. We found that Fe-NTA induces renal ODC activity and DNA synthesis and promotes N-diethylnitrosamine (DEN) induced renal tumorigenesis in rat. The toxicity of Fe-NTA increases with the increasing age of animals and correlates with the accumulation of 4 hydroxy-2 normal (HNE) modified protein adducts. We also showed that Fe-NTA is a potent hepatic tumor promoter and acts through a mechanism elaborating oxidative stress. Fe-NTA down regulates hepatic and renal quinone reduces (QR) activity, which may be responsible for observed renal and hepatic injury. Feeding of dietary agents such as garlic oil, nordihydroguaretic acid (NDGA) and vitamin-E suppress Fe-NTA induced nephrotoxicity. These agents also serve as potent chemopreventive agents against tumorigenesis induced in rodents treated with this iron comkplex. In an iron-overload model was showed that benzoyl peroxide (BPO) / 12-O-tetradecanoyl phorbol 13-acetane (TPA)-mediated cutaneous tumor promotion in 7-12-dimethyl benz(a)anthracene (DMBA)-initiated mice is sugmented. We also observed that continuous exposure to even small doses of iron enhances the tumor promotion ability of TPA/BPO/UVE in DMBA initiated marine skin. Free radicel generating organic peroxides and hydroperoxides are known to promote tumorigenesis and enhance the malignant conversion of papillomass to carcinomas in mouse skin and iron has been shown to participate in free radical generating reactions. We used various peroxides and hydroperoxides (BPO, cumene hydroperoxie, hydrogen peroxide) as stage-I and stage-II tumor promoters and studied their effects in iron overload animals on the malignant conversion of bengin papillomas to carcinomas. We observed that iron-overload augments stage-I and stage-II of tumor promotion and enhances the malignant conversion of papillomass to carcinomas in mouse skin. To further confirm the role of iron in sugmenting tumorigenosis, we conducted similar experiments in iron deficient animals. We observed that these agents cause reduced toxicity and carcinogenecity in mice treated with the chemopreventive agents. Our data indicate that iron exposure may increase the risk of liver and kidney damage as well as many enhance the risk of cancer development in the exposed population.
 

Polycyclic Aromatic Hydrocarbons in Environment and Associated Challenges

Dr. (Mrs.) Neeta Thacker*

Polycyclic aromatic hydrocarbons (PAHs) are formed mainly as a result of incomplete combustion or high temperature pyrolytic process during burning of fossil fuels / organic materials, as well as in natural processes such as carbonisation. Aromatic hydrocarbons on reaction with other atmospheric pollutant viz. NOx, SO2, O2, Cl2 etc. may form hetro-PAHs or substituted PAHs. The carcinogenicity and mutagenicity of many of these hetro-PAH compounds is greater than their parent compounds. It has been reported as early as 1976 that between 45 and 55% of the carcinogenic activity of airborne particulate matter is associated with PAHs and by many other halogenated substituted cyclic aromatic hydrocarbons like polychlorinated dibenzo-p-dioxins (PCDDs), Polychlorinated dibenzofurans (PCDFs) etc. PAHs are large group of organic compounds with two or more benzene rings. They have relatively low solubility in water but are highly lipophilic. Almost the total amount of PAH with low vapour pressure in the air is adsorbed onto the particles. PAH can undergo photodecomposition when exposed to UV light from solar radiation. There are several hundred PAHs compounds occurring in environment with potential carcinogenic/ mutagenic activity.

People exposed to toxic air pollutants at sufficient concentrations and durations may have an increased chance of getting cancer or experiencing other serious health effects. These health effects can include damage to the immune system, as well as neurological, reproductive (e.g. reduced fertility), developmental, respiratory and other health problems. In addition to exposure from breathing air toxics some toxic air pollutants can deposit onto solids or surface waters, where they are taken up by plants and ingested by animals and are eventually magnified up through the food chain.

At present, no limit of PAHs either in air or in water environment has been prescribed in India. Also there is not any provision of granting consent based upon these compounds in the effluent and emissions from the stationary and mobile sources.
* Scientist, National Environmental Engineering Research Institute, Nagpur – 440 020
Measurement of PAHs is helpful in assessing the existing level of PAHs in source emissions, ambient air, effluents, surface water, sludge/sediment. This will help in the development of data bank of PAHs levels in water and air, formulation and development of standards for ambient air quality, surface water, source emissions and effluents, granting consent based on PAHs to the relevant sources, identification and record of sources of PAHs and formulations of abatement and control strategies of PAHs in the environment.

PCDDs and PCDFs are extremely potent in producing a variety of effects in animals, at dose levels several orders of magnitude lower than most other chemicals of environmental interest. PCDDs and PCDFs are created inadvertently by a host of industrial activities (agrochemicals, pharmaceuticals etc.) in which chlorine based compounds are exposed to high heat in the presence of organic materials. These compounds are highly stable and bio-accumulative.

It was always felt that PCDDs and PCDFs are emitted predominantly due to combustion of hydrocarbons. USEPA's Boiler and Industrial Furnace (BIF) regulations, the Cement Kiln Dust (CKD) report, the Dioxin Reassessment and now the Maximum Achievable Control Technology (MACT) regulations all rely on this concept. No definitive mechanism have been demonstrate to account for dioxin formation and emissions in cement kilns. It is understood and generally accepted that there is a relationship between dioxin emissions and temperature. But debate on at what temperature ranges and at what locations dioxins formation takes place is still continuing. There is an additional belief that high hydrocarbons content in the kiln raw feed may produce high dioxin emissions. This is true for certain kilns but for other it is not. EPA's proposed MACT standard (1999) of 0.2 ng/dscm (TEQ) for incinerators, cement kilns that burn hazardous wastes is based on temperature formation scenario.

Dioxins and furans are also included in the inventory of Persistent Organic Pollutants (POPs), for which United Nations Environment Programme (UNEP) has established a treaty with 50 nations (2001, Stockholm convention) by committing governments to eliminate productions and environmental releases of these chemicals. This 2001 Stockkholm convention of POPs has now become legally binding from May 17, 2004, as announced by UNEP recently. The efforts for estimating and accounting the contamination of all such chemicals in environmental samples are being made.

 

Mechanism Based on Biomarker for Toxicity Assessment of Chemicals
 with particular reference to metals and pesticide

Prahlad K Seth

Scientist-in-Director’s Grade
Industrial Toxicology Research Centre
Post Box 80, M.G. Marg, Lucknow-226001
 

A large number of chemicals are being added to our environment everyday to which human beings of all ages get exposed directly or indirectly.  Among these, pesticides and metals here aroused great concern due to their widespread use in large quantum in developing countries. Depending on their structure and properties, these chemicals interact with cellular biomolecules and exert adverse effects.  Pesticides or metals in low doses generally do not exert an apparent adverse effect, however, with the built up of sufficient concentration in tissues, adverse effects become apparent.  Individuals exhibit differential response to chemicals depending on their age, sex and genetic make up and these factors also determine their susceptibility to chemicals.  The levels of pesticides, metals or chemicals, the enzymes altered by them or the biomolecules with which the chemical binds serve as the biomarkers for the health risk assessment. The assay of the levels of pesticides and their metabolites or metals in blood and tissues serve as the biomarkers of exposure, the changes caused in enzymes and tissue macromolecules following exposure serve as the biomarkers of effect and the enzymes responsible for the metabolism of chemicals and the molecular targets of the chemicals modulated genetically serve as the marker of susceptibility.  The advances in genomics and proteomics have provided newer tools to develop mechanism based biomarkers of predictive value.  Metallothionein gene expression in peripheral blood lymphocytes have been used as biomarker of cadmium exposure. An assessment of ALAD and Vitamin D receptor (VDR) genes can help in identifying population susceptible to lead. Likewise an assay of variant alleles of PONI can help in determining the susceptibility to organophosphate compounds. Our studies to validate biomarkers of exposure and effect have recently demonstrated the presence of significant constitutive mRNA and protein expression of xenobiotic metabolizing CYP2E1 and 3A and inducible CYP1A1 in rat blood lymphocytes.