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Additional toxicological data

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Administrative data

Endpoint:
additional toxicological information
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
not reported
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: No data on GLP or if test is performed to regonsised method. No information of purity.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1982
Report Date:
1982

Materials and methods

Type of study / information:
Effect of iv enjection of test substance.
Variety of in vitro tests using rat cells.
Test guideline
Qualifier:
no guideline followed
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent

Results and discussion

Any other information on results incl. tables

Cell viability studies

In the presence of graded amounts of DOTC, thymocyte survival decreased in a dose related and time-dependent fashion when compared with the thymocyte loss in the control cultures. After a 24-hr incubation with 50 µg DOTC, survival was only some 25-30% of the control values. With concentrations of 0.5 µg/ml (1.2 µM-DOTC), thymocyte survival still showed a considerable decrease.

Lymphocyte Transformation

The blast transformation of thymocytes was inhibited in a dose-related manner in the presence of graded concentrations of DOTC. In concentrations of 0.5 µg DOTC/ml incorporation was completely inhibited.

DOTC was shown to have similar effects on the transformation of lymphocytes from the spleen as on those from the thymus. and again the effects were similar in PHA- and Con A-stimulated cultures and also in splenocyte cultures incubated with LPS.

Glucose metabolism studies

Glucose uptake showed some increase at a concentration of only 5 µM. Maximal stimulation of glucose consumption occurred at 120 µM for DOTC further increases in the exposure levels progressively decreased glucose consumption.

The increased amount of glucose consumed by thymocytes incubated with DOTC was not completely metabolized but was largely converted to lactate and pyruvate. Thus conversion is mainly by the glycolytic pathway, with little oxidation by the TCA cycle. Lactate and pyruvate production was stimulated maximally at the concentration of DOTC that also induced maximum glucose consumption.

The oxygen consumption of the thymocytes showed a slight, but dose-related, decrease in incubations with the test compound. At maximum stimulation of the substrate uptake. Oxygen consumption was never reduced by more than 30%, and at lower organotin concentrations it was only slightly diminished. This is notable, since the accumulation of lactate and pyruvate showed that the increased amount of glucose consumed undergoes little oxidative metabolism.

At organotin levels up to those inducing maximum stimulation of the substrate consumption. the number and viability of rat thymocytes was not affected during the 4-hr incubation period. Cell survival declined at higher exposure levels but after a 4-hr incubation it was never reduced by more than 10% when scored with nigrosin exclusion.

Applicant's summary and conclusion

Conclusions:
DOTC induces lymphcytotoxicity both in vitro and in vivo.