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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
other: summary of experimental results
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Cross-reference
Reason / purpose for cross-reference:
reference to same study
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
other: summary of experimental results
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
secondary literature
Reason / purpose for cross-reference:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Limited details provided, the study was cited as a short abstract. A subchronic (13-14 weeks) feeding study performed in rats, performed by the same laboratory that authored the review publication. Subchronic study: 20 males and 20 females per dosign group were administered 0, 4, 20 and 100 ppm in the diet.
GLP compliance:
not specified
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
Juvenile rats
Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13-14 week subchronic study
Frequency of treatment:
Daily
Dose / conc.:
0 ppm
Remarks:
subchronic study (nominal in diet)
Dose / conc.:
4 ppm
Remarks:
subchronic study (nominal in diet)
Dose / conc.:
20 ppm
Remarks:
subchronic study (nominal in diet)
Dose / conc.:
100 ppm
Remarks:
subchronic study (nominal in diet)
No. of animals per sex per dose:
Subchronic study: 20/sex
Control animals:
yes
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Decreased weight gain at 100 ppm
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
At 100 ppm food intake was decreased in both sexes; and in females only at 20 ppm
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
effects observed, treatment-related
Description (incidence and severity):
Decreased in the highest dose
Ophthalmological findings:
not specified
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
During the coagulation studies in week 11, thromboplastin time, partial thromboplastin time, and thrombin time were slightly and dose-dependently increased in male rats at 20 and 100 ppm, where as fibrinogen and thrombocyte count were not altered
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
100 ppm, increased serum alkaline phophatase and albumin and decreased gamma-globulin as well as an increased albumin-globulin quotient
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
decreased organ weights of thymus, iliac lymph node (F only) and thyroid and an increased weight of the adrenals (M only) were found.
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
at 500 ppm, atrophy of the thymus and lymph nodes in terminally sacrificed animals was observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
not specified
Dose descriptor:
NOEL
Remarks:
13-week study
Effect level:
4 ppm
Based on:
test mat.
Remarks:
lowest dose tested
Sex:
male/female
Dose descriptor:
LOEL
Remarks:
13-week study
Effect level:
20 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
food consumption and compound intake
haematology
Dose descriptor:
dose level: 13-week study
Effect level:
100 ppm
Based on:
test mat.
Remarks:
high dose
Sex:
male/female
Basis for effect level:
body weight and weight gain
clinical biochemistry
food consumption and compound intake
organ weights and organ / body weight ratios
Critical effects observed:
not specified
Conclusions:
In the 13 -14 week subchronic study with rats fed 0, 4, 20, 100 ppm, the NOAEL was 4 ppm based on slight prolongation of coagulation times in males and decreased food consumption in females at 20 ppm (LOAEL). At 100 ppm, there was a continued decrease in food consumption and weight gain along with changes in serum biochemistry and decreased weights of thymus, lymph node and thyroid (males and females) and increased adrenal weight (males).
Executive summary:

In the 13 -14 week subchronic study with rats fed 0, 4, 20, 100 ppm, the NOAEL was 4 ppm based on slight prolongation of coagulation times in males and decreased food consumption in females at 20 ppm (LOAEL). At 100 ppm, there was a continued decrease in food consumption and weight gain along with changes in serum biochemistry and decreased weigths of thymus, lymph node and thyroid (males and females) and increased adrenal weight (males).

Data source

Reference
Reference Type:
review article or handbook
Title:
Unnamed
Year:
1986
Report date:
1986

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Limited details provided, the study was cited as a short abstract. A subacute (4 weeks) feeding study performed in rats, performed by the same laboratory that authored the review publication. Five males and five females per dosing group were dosed at 4 dosing levels, 4, 20, 100 and 500 ppm in the diet.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(tributyltin) oxide
EC Number:
200-268-0
EC Name:
Bis(tributyltin) oxide
Cas Number:
56-35-9
Molecular formula:
C24H54OSn2
IUPAC Name:
tributyl[(tributylstannyl)oxy]stannane
Details on test material:
Reported as Tributyltin oxide (TBTO) , with the synonyms bis (tri-n-butyltin) oxide or hexa-n-butyldistannoxane

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals or test system and environmental conditions:
Juvenile rats

Administration / exposure

Route of administration:
oral: feed
Vehicle:
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4-week dose range finding study
Frequency of treatment:
Daily
Doses / concentrationsopen allclose all
Dose / conc.:
4 ppm
Remarks:
dose range finding study (nominal in diet)
Dose / conc.:
20 ppm
Remarks:
dose range finding study (nominal in diet)
Dose / conc.:
100 ppm
Remarks:
dose range finding study (nominal in diet)
Dose / conc.:
500 ppm
Remarks:
dose range finding study (nominal in diet)
No. of animals per sex per dose:
Dose range-finding study: 5/sex
Control animals:
not specified

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Description (incidence and severity):
No effects at 4 or 20 ppm; at 100 ppm decreased absolute thymus weights (males); at 500 ppm decrease in aboslute and relative weight of thymus and lymph nodes
Mortality:
mortality observed, treatment-related
Description (incidence):
No effects at 4 or 20 ppm; at 100 ppm decreased absolute thymus weights (males); at 500 ppm decrease in aboslute and relative weight of thymus and lymph nodes
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
No effects at 4 and 20 ppm; at 100 and 500 ppm slightly decreased weight gain
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
No effects at 4 and 20 ppm; at 100 and 500 ppm, decreased food consumption
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
4-week study: no effects at 4 or 20 ppm; at 100 pm, decreased absolute weight of thymus (males); at 500 ppm, decreased absolute and relative weights of thymus and lymph nodes
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
4-week study: no effects at 4, 20, or 100 ppm; at 500 ppm a reduction of the lymphocyted content in the thymus and in thyus dependent region of the spleen and lymph node was demonstrated in animals which had died prematurely (3M/2F) and surviving animlas
Histopathological findings: neoplastic:
not specified

Effect levels

open allclose all
Dose descriptor:
NOEL
Remarks:
4 week study
Effect level:
20 ppm
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LOEL
Remarks:
4-week study
Effect level:
100 ppm
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
food consumption and compound intake
organ weights and organ / body weight ratios

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In a 4-week dose range-finding study rats were fed 4, 20, 100, or 500 ppm tributyltin oxide. The NOAEL was 20 ppm based on decreased food consumption and weight gain in males and females and decreased thymus weights in males at 100 ppm, the LOAEL.
Executive summary:

In a 4-week dose range-finding study rats were fed 4, 20, 100, or 500 ppm tributyltin oxide. The NOAEL was 20 ppm based on decreased food consumption and weight gain in males and females and decreased thymus weights in males at 100 ppm, the LOAEL.