Experimental studies on insecticides commonly used in India.

Using hexachlorocyclohexane (BHC) as a model histopathological, histoenzymological, biochemical, and electrophoretic studies were undertaken to find out certain parameters for early diagnosis of liver cancer. In addition, cytogenetic studies were carried out to evaluate the effect of BHC feeding on mitotic and meiotic divisions. The results of these investigations suggest that there is a significant change in liver weight in experimental group. Histologically, liver cells follow a definite sequential cellular alteration ultimately leading to liver tumor. Histochemically, well defined pattern of glycogen accumulation and iron distribution in hepatocytes was observed. The electron-microscopic observation demonstrated prominently the proliferation of agranular endoplasmic reticulum in early stages. The distribution of certain enzymes linked with plasma membrane, lysosomes, and mitochondria showed the functional alteration of these organelles both in neoplastic nodules and tumours induced by BHC. The biochemical changes observed in gluconeogenic enzymes (G6Pase and F1,6dipase) and dehydrogenases (LDH, ICDH, and MDH) at different duration of exposure to BHC indicated decrease in enzyme activity of both gluconeogenic pathway and tricarboxylic acid cycle, linked with energy metabolism. These changes tend to recover with discontinuation of BHC but 8 months continuous feeding produces irreversible changes in G6Pase activity. Using polyacrylamide gel electrophoresis technique a change in serum proteins and LDH isoenzymes was observed. However, extrapolation of these findings to human situation needs more extensive studies, taking into account all possible variables, such as the DDT and BHC load in our environment and the body burden resulting there from.

Early changes in serum protein and liver LDH isoenzymes in mice exposed to technical grade hexachlorocyclohexane (BHC) and their possible relationship to liver tumours.

Mice were exposed to hexachlorocyclohexane (BHC) in order to study the changes in the serum protein pattern and in the LDH isoenzymes of the liver. After 2 months of exposure the protein pattern showed a new band which persisted even after the development of a tumour. The LDH isoenzymes pattern showed a gradual decrease of the faster moving LDH-1 and LDH-2 bands which later disappeared completely when hepatic tumours formed. The significance of these results is discussed.

Erosion of nails following thallium poisoning: a case report.

This case report describes a patient with thallium poisoning caused by repeated exposure to low doses of thallium. Alopecia and nail changes were the most prominent features of this case. There was dystrophy of nails in the form of whitish lunular stripes. This is the first report of complete erosion of proximal parts of nails following thallium poisoning. This case is the first report of thallium poisoning from India occurring from repeated low dose exposure.

Dominant-lethal study of technical-grade hexachlorocyclohexane in Swiss mice.

Male Swiss mice, 6-8 weeks old, were given a diet containing technical-grade hexachlorocyclohexane (BHC) at 500 ppm continuously for 4, 6 and 8 months. After the completion of the scheduled exposure period, the males were sequentially mated with 2-3 untreated virgin females at weekly intervals for 8 weeks. The females were autopsied at mid-term pregnancy for evaluation of dominant-lethal mutation. The number of dead implants, including deciduomas and dead embryos, showed a significant increase. Similarly, the percentage fertility and live embryos per female showed a decline when compared with the control

Humoral immunologic dysfunction in silicosis.

Immunoglobulins may play an important role in the evolution of silicosis, and their determination may serve as a helpful criterion in the diagnosis of silicosis. Serum immunoglobulin levels were studied in slate pencil workers (130) exposed to high concentrations of silica dusts and non-exposed controls (50). Significantly higher levels of immunoglobulins were observed in the silica exposed individuals. A rising trend in the serum IgG from a mean of 1373 mg/dl in control group to 2193.68 mg/dl in exposed group (conglomerate) and IgM from 140.51 mg/dl in control to 201.19 mg/dl in exposed group (conglomerate silicosis) was observed with increase in the duration of dust exposure. Highest mean levels of IgG (2193.60 mg/dl) and IgM (201.19 mg/dl) were observed in the workers having conglomerate silicosis. The results indicate that though, the levels of immunoglobulins were raised in subjects exposed to silica, this parameter may be of limited value for determining progressive of silicosis.

Humoral immunological profile of workers exposed to asbestos in asbestos mines.

Humoral immunological profile including immunoglobulins IgG, IgA, IgM, C-reactive protein, rheumatoid factor, antinuclear antibodies and circulating immune complexes were studied in a representative sample of 36 workers suffering from asbestosis (group A), 35 workers who are exposed to asbestos but not having evidence of asbestosis (group B) and 28 control workers (group C). Mean IgG and IgA levels were found to be significantly higher in the two exposed groups than in the controls. Circulating immune complexes of IgG, IgA and IgM class were detected in a significant percentage of cases in exposed groups than in controls. In groups A and B, the percentage of positive ANF cases was much higher than in the controls. The results suggest that immunological changes are associated with exposure to asbestos and these may play an important role in the pathogenesis of the disease process.

Studies on glucose-6-phosphatase, fructose-1,6-diphosphatase activity, glycogen distribution and endoplasmic reticulum changes during hexachlorocyclohexane induced hepatocarcinogenesis in pure inbred Swiss mice.

Inbred Swiss mice were fed hexachlorocyclohexane (BHC) at 500 ppm dose level in diet for 2, 4, 6 and 8 months. Later BHC was discontinued for 4 months and subsequently the animals were refed BHC for 1 month. Glucose-6-phosphatase (G6Pase) and fructose-1,6-diphosphatase (FDPase) activity was studied at different time intervals accompanied with changes in glycogen distribution and endoplasmic reticulum (ER) proliferation in hepatocytes. G6Pase and FDPase showed a decline in activities on BHC feeding. The activities of these enzymes showed recovery on BHC discontinuation. The changes were progressive with duration of exposure. After 6 months exposure the biochemical changes became more resistant to recovery. Maximal changes occurred in 8 month-exposure and the changes were irreversible. Glycogen accumulation and depletion followed a definite pattern. After two months of BHC feeding, increase in parenchymal glycogen storage zones was observed. In the later stage of hepatocarcinogenesis and specially in tumors, glycogen was depleted considerably. Smooth endoplasmic reticulum (SER) proliferation was recorded around the 3rd and 4th month. The correlation between glycogen accumulation, SER proliferation, G6Pase and FDPase activity is discussed.

Distribution of isomers of BHC and related histopathology of liver in hexachlorocyclohexane (technical grade BHC) fed mice.

In an attempt to correlate body burden and related liver histopathology after exposure to 500 ppm benzene hexachloride, 6- to 8-wk-old male and female mice were fed benzene hexachloride with their mash diet for a 6-month period. The mice were divided into 8 groups (12/group; 6 experimental, 6 control) and were sacrificed by group monthly. During the first month, 3 groups of mice were sacrificed after 10, 20, and 30 days of treatment, respectively. A dose-related increase in liver weight was found in test animals (P less than .01). The histopathology of liver showed clear, oval cells; hypertrophied cells with foci; and neoplastic nodules that were apparent during the final 3- to 6-month period. Few oval and hypertrophied cells were found in control animals. The alpha isomer concentration of benzene hexachloride rose during the first 2 months of treatment, but declined after that time. A transient rise was noted for the beta isomer concentration of benzene hexachloride at the end of the 6-month period. The gamma isomer concentration was elevated during the initial 3 months of treatment, but declined during the subsequent 3 months. The results present definitive changes suggestive of precancerous states.

Silica exposure and serum angiotensin converting enzyme activity.

BACKGROUND: Silicosis is known in industrial workers for centuries. Till recently, the mainstay of its diagnosis and progress was clinical examination of the respiratory system, pulmonary function test and chest radiography. Several biomarkers such as serum angiotensin converting enzyme (ACE) activity have been examined to determine the extent of silicosis. OBJECTIVE: To elucidate the effect of age, gender, duration of exposure to silica dust, smoking habit, and pulmonary function status on the serum ACE activity among quartz stone workers without disease. METHODS: A cross-sectional study was carried out on 134 (111 men and 14 women) workers of quartz stone crushing units were studied. Standard diagnostic criteria were used for diagnosing silicosis and tuberculosis. Pulmonary functions of the participants were also assessed. RESULTS: The mean±SD age for participants was 26.1±6.3 years (26.6±6.3 for men and 21.9±4.3 for women). The mean±SD duration of exposure was 1.1±1.9 years. In the present study, only one case of silicosis and eight cases of tuberculosis were found. The mean±SD serum ACE levels for those with and without respiratory disease were 68.44±11.61, and 66.9±14.4 IU/L, respectively (p>0.05). CONCLUSION: We could not observe any association between serum ACE activity and age, gender, duration of exposure, smoking habits and pulmonary function status. However, elevated levels of serum ACE was found in a solitary case of silicosis.

Carcinogenicity of hexachlorocyclohexane (BHC) in pure inbred swiss mice.

Inbred Swiss mice were treated with technical BHC (1) orally with the diet or by intubation and (2) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Symptoms of intoxication in the form of convulsions and tendency of circling in one direction with drooping ears were observed alongwith corneal opacity 40 weeks after the experiment. Oral BHC treatment resulted in a significant increase in the incidence of liver tumours and tumours of lymphoreticular tissue. Males and females were equally susceptible. Skin painting of mice did not significantly increase the incidence of tumour.

Carcinogenicity of DDT (dichlorodiphenyl trichloroethane) in pure inbred Swiss mice.

Inbred Swiss mice were treated with technical DDT (1) orally with the diet or by intubation; (2) subcutaneously and (3) by skin painting. The total duration of the experiment was 80 weeks. There was no difference in body growth and mortality between the experimental and control groups. Toxic manifestations of DDT were observed in treated mice in the form of tremor, convulsions and corneal opacity usually after 40 weeks. Oral and subcutaneous DDT treatment resulted in a significant increase in the incidence of tumours mainly of lymphoid tissues, lung and liver. The highest tumour incidence was recorded in the group of mice receiving DDT by subcutaneous injections. Males and females were equally susceptible. No evidence of carcinogenicity was observed in the painted group.

Clinical and biochemical investigations to evolve early diagnosis in workers involved in the manufacture of hexachlorocyclohexane.

365 individuals exposed to hexachlorocyclohexane (HCH) during its manufacture were studied and compared with 146 controls. These 502 cases were divided into five groups on the basis of serum total HCH levels. Exposure was mainly through skin. Results indicate that neurological symptoms reported were due to recent exposure to HCH and were related to the intensity of exposure. ECG abnormalities were seen in exposed cases. A significant positive correlation to liver related enzymes gamma GT, LAP and Alp. P was observed. beta-globulins significantly increased along with an increase in total HCH. Changes in IgM levels were similar as observed in IgA. Remarkably high concentration of HCH residues were found in the serum samples of all exposed workers. beta-HCH contributed more than 80% of the total HCH built up. Presence of circulating immune complexes was also detected in representative samples. Further, repeated biological monitoring was advised to be carried out among such workers exposed to HCH, to evaluate signs of severe health impairment in them.