Toxicological profile for arsenic

Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers.

Health effects of chronic pesticide exposure: cancer and neurotoxicity.

Knowledge on heritable changes in gene expression that result from epigenetic events is of increasing relevance in the development of strategies for prevention, early diagnosis and treatment of cancer. Histone acetylation and DNA methylation are epigenetic modifications whose patterns can be regarded as heritable marks that ensure accurate transmission of the chromatin states and gene expression profiles over many cell generations. Importantly, patterns and levels of DNA methylation and histone acetylation are profoundly altered in human cancers. Accumulating evidence suggests that an epigenetic cross-talk, i.e. interplay between DNA methylation and histone acetylation, may be involved in the process of gene transcription and aberrant gene silencing in tumours. Although the molecular mechanism of gene activation is relatively well understood, the hierarchical order of events and dependencies leading to gene silencing in the course of cancer development remain largely unknown. While some studies suggest that DNA methylation patterns guide histone modifications (including histone acetylation and methylation) during gene silencing, other studies argue that DNA methylation takes its cues primarily from histone modification states. In this review, we summarize current knowledge on the interplay between DNA methylation and histone modifications during gene silencing and its importance in the integration of environmental and intrinsic stimuli in the control of gene expression. We also discuss the importance of an epigenetic cross-talk in the protection against genetic changes in response to environmental genotoxins as well as the implication for cancer therapy and prevention.

Epigenetic interplay between histone modifications and DNA methylation in gene silencing

The article contains sections titled:



1.	Arsenic	
1.1.	Introduction	
1.2.	Physical Properties	
1.3.	Chemical Properties	
1.4.	Occurrence	
1.5.	Production	
1.5.1.	Production of Arsenic Trioxide	
1.5.1.1.	Ore Dressing	
1.5.1.2.	Pretreatment of Arsenical Materials	
1.5.1.2.1.	Roasting	
1.5.1.2.2.	Alternative Pretreatments of Arsenical Materials	
1.5.1.3.	Production of Refined As2O3	
1.5.2.	Production of the Metal	
1.6.	Treatment of Arsenic-Containing Byproducts	
2.	Arsenic Compounds	
2.1.	Arsenic Trioxide	
2.2.	Arsenous Acid	
2.3.	Arsenic Pentoxide	
2.4.	Arsenic Acid	
2.5.	Arsenic Sulfides	
2.6.	Arsenic Halides	
2.7.	Arsenic Hydride and Arsenides	
2.8.	Organoarsenic Compounds	
2.8.1.	Aliphatic Organoarsenic Compounds	
2.8.2.	Aromatic Organoarsenic Compounds	
3.	Uses and Economic Aspects	
4.	Stabilization of Arsenic for Safe Disposal	
5.	Recycling	
6.	Safety Measures	
7.	Toxicology

Arsenic and Arsenic Compounds

Arsenic in ground water has been found above the maximum permissible limit in six districts of West Bengal covering an area of 34 000 km2 with a population of 30 million. At present 37 blocks of these six districts by the side of the River Ganga are affected and about 800 000 people from 312 villages/wards are drinking arsenic contaminated water and amongst them at least 175 000 people are showing arsenical skin lesions. The source of arsenic is geological. We have analysed thousands of tube-well water samples from these six districts for four arsenic species namely, arsenite, arsenate, monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA). We could detect no MMAA or DMAA in any of these samples. In urine, DMAA and MMAA are the predominant species along with arsenite and arsenate. The techniques we used for the determination and speciation of arsenic are: (i) separation of arsenite and arsenate from water by sodium diethyldithiocarbamate in chloroform followed by FI-HGAAS; (ii) spectrophotometry using Ag–DDTC in chloroform with hexamethylenetetramine as absorbing solution; (iii) ion-exchange separation of arsenite and arsenate from water followed by FI-HGAAS; and (iv) for analysis of inorganic arsenic and its metabolites in urine, FI-HGAAS was used after separation of the species by a combined cation–anion-exchange column. Total arsenic in urine was determined by FI-HGAAS after acid decomposition. The most toxic species, arsenite, is present in ground water at about 50% of the total arsenic level, and more than 90% of the total arsenic in urine is inorganic arsenic and its metabolites.

Arsenic in ground water in six districts of West Bengal, India: the biggest arsenic calamity in the world. Part I. Arsenic species in drinking water and urine of the affected people

Cancer mortality was studied in 1,393 persons exposed to high air concentrations of inorganic arsenicais for varying lengths of time during the manufacture and packaging of pesticides at a plant in Baltimore, Maryland. Employees consisting of 1,050 males and 343 females were traced for the period 1946 to 1977, and vital status was determined for 86.9% of males and 66.8% of females. The observed number of deaths from all and selected causes was compared with the number expected from the Baltimore City mortality experience in terms of the Standardized Mortality Ratio (SMR). A significantly increased SMR was found for lung cancer and anemias in males. The SMR for lung cancer was especially high in males with presumed high exposure to arsenicais. A dose-response relationship was suggested by the SMR for lung cancer which increased with increasing duration of exposure to arsenicais, but no such relationship was evident for nonarsenicals. Although smoking habits could not be examined in the study subje...

Mabuchi K

Papers

Lung cancer among pesticide workers exposed to inorganic arsenicals.