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Administrative data

Endpoint:
immunotoxicity: oral
Remarks:
other: immunotoxicological evaluation
Type of information:
other: publication
Adequacy of study:
key study
Study period:
1986
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The evaluation of the study is hampered by lacking information concerning the Guidelines for testing and the quality of the tested substance. Moreover, the study does not investigate concomitant effects of mortality or clinical toxicology.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1988
Report date:
1988

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Female rats were treated with 0, 10, 100, 200 mg/kg bw radiolabelled 4,4'-thiobis(6-tert-butyl-3-cresol) once daily for 14 consecutive days. After 14 days the immunological response was investigated.
GLP compliance:
no

Test material

Constituent 1
Details on test material:
- Name of test material (as cited in study report): TBBC
No further information mentioned in publication.

Test animals

Species:
mouse
Strain:
CB6F1
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Litton Bionetics Inc.
- Age at study initiation: 5 -6 weeks
- Weight at study initiation: 17 - 20 g
- Fasting period before study: not mentioned
- Housing: four animals together in plastic shoebox cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 40 - 60
- Air changes (per hr): not mentioned
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: unspecified
Vehicle:
corn oil
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
14 days
Frequency of treatment:
once daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 10, 100, 200 mg/kg bw
Basis:
no data
No. of animals per sex per dose:
5 - 8
Control animals:
yes, concurrent vehicle

Examinations

Observations and clinical examinations performed and frequency:
CAGE SIDE OBSERVATIONS: No data

OTHER:
Detailed analysis of various cell types involved in immunology.

Results and discussion

Results of examinations

Clinical signs:
not examined
Mortality:
not examined
Body weight and weight changes:
not examined
Food consumption and compound intake (if feeding study):
not examined
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Gross pathological findings:
not examined
Details on results:
All immunological parameters were measured 24 hr after the last chemical exposure. When indicated, animals were immunized during the exposure.
TBBC produced a decrease in the peak IgM (44%) and peak IgG (48%) antibody response to sheep erythrocytes (SRBCs), but had no effect on the delayed hypersensitivity response (DHR) to keyhole limpet hemocyanin (KLH).
Paradoxically, TBBC caused an overall increase in the number of splenic cells, a decrease in the percentage of splenic T cells and no effect on the percentage of splenic B cells.
There were no effects on the lymphoproliferative responses to optimal concentrations of concanavalin A(Con A), phytohemagglutinin (PHA), and lipopolysaccharide (LPS), but there was a significant decrease in the mixed lymphocyte response (MLR).
In both the mitogen assays and the MLR there was a dose-related increase in the basal (unstimulated) DNA synthesis of the spleen celIs. Innate immunity, as measured by natural killer (NK) celI activity and serum complement, was significantly increased.
Effects on macrophage function were complex, as an increase or no effect was observed depending on the parameter measured. In the host resistance models, animals were infected with various pathogens 24 hr after the last chemical exposure. Exposure to TBBC caused an increased resistance to challenge with Streptococcus and B16F10 melanoma, a decreased resistance to challenge with PYB6 tumors, and no effect on the resistance to HSV-2, Listeria or Plasmodium.

Specific immunotoxic examinations

Cell viabilities:
effects observed, treatment-related
Humoral immunity examinations:
effects observed, treatment-related
Specific cell-mediated immunity:
effects observed, treatment-related
Non-specific cell-mediated immunity:
effects observed, treatment-related
Other findings:
effects observed, treatment-related

Effect levels

Dose descriptor:
NOAEL
Remarks on result:
not determinable
Remarks:
no NOAEL identified

Any other information on results incl. tables

none

Applicant's summary and conclusion

Conclusions:
Upon treatment of female rats with 0, 10, 100, 200 mg/kg bw radiolabelled 4,4'-thiobis(6-tert-butyl-3-cresol) once daily for 14 consecutive days, the animals expressed complex imunological toxicity effects from 10 mg-kg bw onwards.