Bis(tributyltin) oxide

Endpoint summary

Description of key information

Subacute and subchronic feeding studies:

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. In the following 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).

Subacute inhalation study:

In an inhalation study with tributyltin oxide rats were exposed in nose only chambers for 4 hours 5 days a week for 21 -24 treatments for 29 -32 days. The acutal chamber concentration and particle size distribution in the exposure chamber were controlled repeatedly; dose groups included sham exposed animals, 0.03 mg/m³ vapour, 0.16 mg/m³ vapour, and 2.8 mg/m³ aerosol (90 -100% inhalable particles). The higher of the two vapour concentration corresponds to the equilibriium vapour pressure of the test material in the chamber atmosphere and can be regarded as a no-effect level. In rats exposed to the 2.8 mg/m³ aerosol, 11/20 animals died and a decrease in food consumption and weight gain was observed; other effects at this concentration included changes in hematology parameters, inflammatory reactions in the respiratory tract, and lymphotoxic effects. The NOAEL was determined 0.16 mg/m³. The LOAEL was determined to be 2.8 mg/m³.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Reference 1

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 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

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:

4-week dose range finding study

Frequency of treatment:

Daily

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

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

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

Critical effects observed:

not specified

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.

Reference 2

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).

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The two repeated dose oral toxicity studies, and one of the two available inhalation studies were provided in the same review paper Schweinfurth, H, (1986). The studies were performed by the same laboratory that authored the review paper. As the data were from a secondary source, they are assigned a reliability score of 4 as the reliability of the report cannot be assessed from the limited information presented. Details on whether a relevant guideline, or the GLP status of the studies were not provided. The additional inhalation study, Schweinfurth, H. & Schmidt, M. (1986) was a 10 day subacute study but was not adequate for assessment as there were a number of methodological deficiencies that affected the reliability of the results of the study, as such it was assigned a reliability score of 3.

Justification for classification or non-classification

The substance is included in the group of substances "tributyltin compounds" which is itself included in Annex VI to Regulation (EC) No 1272/2008 with Index Number 050-008-00-3. The entry has been assigned the hazard classification of STOT RE 1 H372 (Causes damage to organs (state all organs affected, if known) through prolonged or repeated exposure (state route of exposure if it is conclusively proven that no other routes of exposure cause the hazard)).