|
Carcinogenicity
studies of organochlorine insecticides viz Dichloro-diphenyl
trichloroethane (DDT), technical grade Hexachlorocyclohexane (HCH),
Lindane (Gamma HCH) and Indian variety of asbestos were
carried out as per UICC protocol. Swiss inbred mice were used
for insecticides where as asbestos carcinogenicity was studied
in Charles Foster rats. The test chemicals were administered
by various routes for periods up to 80 weeks. Along with the
carcinogenicity studies, chronic toxicity of above chemicals
was assessed by sequential histopathological, histochemical,
histoenzymo-logical and biochemical
parameters.
Carcinogenicity of DDT:
Oral and subcutaneous route of exposure resulted in a
significant increase in tumours of lymphoreticular tissue,
lungs and liver with highest tumour incidence being observed
in the group receiving DDT by subcutaneous injections.
Carcinogenicity
of HCH: Technical
grade HCH was found to be a
more potent carcinogen as compared to DDT.
Both male and female animals were susceptible to HCH
induced tumours but incidence of liver tumours was more in
males and those of lymphoreticular system in females.
Following
biological/biochemical changes were found to be useful as
early markers of HCH induced hepatocarcinogenesis.
Decreased
levels of Glucose-6-phosphatase
and Fructose 1,6-Diphosphatase were found in neoplastic
tissues as compared to normal tissue. The activity of these enzymes was nearly absent in the
tumors.
Serum
protein electrophoresis revealed appearance of
specific protein bands at different intervals of time.
There
was gradual reduction in the levels of faster moving LDH
isoenzymes with total absence after formation of liver tumours.
These observations were made simultaneously from liver
as well serum samples.
Histochemically
accumulation of iron and glycogen in the pre-cancerous stages
was a striking observation.
Correlation
between body burden and histopathology showed that
accumulation of HCH isomers in the liver increased up
to two months and then decreased. A second peak was observed
again at 6 months of exposure.
Precisely at this time the liver tumours appeared.
Alpha and Beta HCH peaks coincide with onset of tumours at 6th
month.
Carcinogenicity
of Lindane: With Lindane (Gamma-hexachlorocyclo-hexane)
tumour induction was delayed compared to Technical HCH.
Lindane was more toxic in acute exposures but the chronic toxic effect was relatively less, suggesting that
its long term use is safer than that of technical HCH.
Carcinogenicity
of Asbestos: Lungs of
exposed animals by intra tracheal intubation appeared very
much enlarged in size. There
was diffuse irregular hyperplalsia of alveolar epithelium and
tumours observed were mainly medium sized oat cell carcinoma
and adenocarcinoma metastasing in other organs.
Carcinogenicity studies
Inhalation Toxicity Studies on
Methyl Isocyanine
Reproductive Toxicity
studies in experimental animals
|