Registration Dossier

Administrative data

Endpoint:
immunotoxicity: oral
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
other: special investigation
Rationale for reliability incl. deficiencies:
other: special investigation
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
No information
Author:
Tulinska, J. et al.:
Year:
2000
Bibliographic source:
J. Trace Microprobe Techniques 18, 405-412

Materials and methods

Principles of method if other than guideline:
Male out bred SPF Wistar rats (5 weeks old) were dosed by oral gavage with CBS in CMC for 28 days. Doses were equivalent to 10%; 5% and 2% of the LD50. On day 29 the animals were investigated for general  toxicological and immune functional parameters.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Test substance: Santocure CBS

Test animals

Species:
rat
Strain:
Wistar
Sex:
male

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Duration of treatment / exposure:
Exposure period: 28 day(s)
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0; 400; 1000; 2000 mg/kg bw/day
Basis:

Control animals:
yes, concurrent vehicle
Details on study design:
Observation period: 28 days; no postobservation

Results and discussion

Any other information on results incl. tables

Rats of the two highest dose groups showed a reduction in body weight  from day 22 to day 29.  The highest dose exceeded the MTD. Organ weights of spleen, thymus, and  lymph nodes were decreased as well as the cellularity of thymus, spleen, and bone marrow. Rats of the 1000 mg/kg-group showed reduced spleen weight and reductions in cellurarity of thymus and bone marrow. The ConA-mediated proliferation of lymphocytes was slightly decreased in  animals of the 1000 and 2000 mg/kg-groups whereas the STM-mediated  proliferation of spleen lymphocytes was enhanced in the 400 and 1000 mg/kg-groups. The number of PFC was slightly increased in the 400 mg/kg- group and was decreased in the 1000 and 2000 mg/kg-groups. The spleen cellurarity showed a dose-dependent decrease. The phagocytic activity of the leukocytes remained unaffected whereas a slight decrease in monocyte activity was observed in all CBS treated rats.

Applicant's summary and conclusion

Executive summary:

Male out bred SPF Wistar rats (5 weeks old) were dosed by oral gavage with CBS in CMC for 28 days. Doses were equivalent to 10%; 5% and 2% of the LD50. On day 29 the animals were investigated for general  toxicological and immune functional parameters.

Rats of the two highest dose groups showed a reduction in body weight  from day 22 to day 29.  The highest dose exceeded the MTD. Organ weights of spleen, thymus, and  lymph nodes were decreased as well as the cellularity of thymus, spleen, and bone marrow. Rats of the 1000 mg/kg-group showed reduced spleen weight and reductions in cellurarity of thymus and bone marrow. The ConA-mediated proliferation of lymphocytes was slightly decreased in  animals of the 1000 and 2000 mg/kg-groups whereas the STM-mediated  proliferation of spleen lymphocytes was enhanced in the 400 and 1000 mg/kg-groups. The number of PFC was slightly increased in the 400 mg/kg- group and was decreased in the 1000 and 2000 mg/kg-groups. The spleen cellurarity showed a dose-dependent decrease. The phagocytic activity of the leukocytes remained unaffected whereas a slight decrease in monocyte activity was observed in all CBS treated rats.