Tin monoxide

Endpoint summary

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: no glp, only similar to guideline

Data waiving:

other justification

Justification for data waiving:

other:

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Route of administration:

oral: feed

Vehicle:

not specified

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

4 and 13 weeks

Frequency of treatment:

daily with diet

Remarks:

Doses / Concentrations:
0.00, 0.03, 0.10, 0.30, 1.00 % Sn in diet
Basis:
nominal in diet

No. of animals per sex per dose:

10 animals per sex per dose per timeframe.

Control animals:

yes

Dose descriptor:

NOEL

Effect level:

> 22 - < 33 other: mg Sn /kg bw day

Based on:

element

Sex:

male/female

Critical effects observed:

not specified

Conclusions:

Severe growth retardation,
decreased food efficiency, slight anaemia and slight histological changes in the liver were
observed with 0.3 70 or more of stannous sulphate.

As NOAL a value of 22-33 mg Sn/kg bw day was determined, no LOAEL was fouind.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

52.9 ng/kg bw/day

Study duration:

subchronic

Species:

rat

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

201/2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study, glp

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

not applicable

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: RccHanTM:WIST rats

Sex:

male/female

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Remarks on MMAD:

MMAD / GSD: 2.7 - 3.0 µm

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

4 weeks (6 hours per day, 5 days per week)

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0 µg/L
Basis:
analytical conc.

Remarks:

Doses / Concentrations:
2.44 µg/L
Basis:
analytical conc.

Remarks:

Doses / Concentrations:
9.19 µg/L
Basis:
analytical conc.

Remarks:

Doses / Concentrations:
87.9 µg/L
Basis:
analytical conc.

No. of animals per sex per dose:

10

Control animals:

yes

Dose descriptor:

NOAEC

Remarks:

systemic

Effect level:

9.91 other: µg/L

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LOAEC

Remarks:

local

Effect level:

2.44 other: µg/L

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: findings were restricted to the lungs and tracheobronchial lymph nodes.

Critical effects observed:

not specified

Summary data are presented below:

Group Exposure level (μg/L) Particle size

Target Achieved MMAD (μm) sg

2 2.3 2.44 3.0 2.54

3 9.1 9.19 3.0 2.41

4 80 87.9 2.7 2.44

MMAD Mass median aerodynamic diameter

sg Geometric standard deviation

The achieved levels were 106, 101 and 110% of the target concentrations for Groups 2, 3 and

4 respectively. The Mass Median Aerodynamic Diameters for Groups 2, 3 and 4 are within

the ideal range (1-3 μm) for a repeat dose inhalation study.

There were no treatment related clinical signs observed during the detailed weekly physical

examination.

Lower body weight gain was evident for males exposed to 9.19 μg/L and 87.9 μg/L and for

all females exposed to tin monoxide. Food consumption was also slightly reduced for males

exposed to 87.9 μg/L.

A statistically significant increase in group mean activated partial thromboplastin times were

evident for males exposed to 9.19 and 87.9 μg/L and all females exposed to tin monoxide.

Group mean venous blood oxygen saturation levels were increased for females exposed to

9.19 μg/L and both sexes exposed to 87.9 μg/L.

Two hours after the completion of exposure in Week 4, tin was detected in the plasma of a

single male and female exposed to 9.19 μg/L and in all animals exposed to 87.9 μg/L. Tin

was not quantifiable in control animals or animals exposed to 2.44 μg/L.

Group mean lung and bronchi weights (adjusted for terminal body weight) were greater than

control for all animals exposed to tin monoxide.

Histopathological changes related to treatment were observed within the lungs (the

accumulation of pigmented and flocculent material within alveoli, variably accompanied by

both diffuse and local aggregations of alveolar macrophages, and increased cellularity of the

BALT), tracheobronchial and mediastinal lymph nodes (increased general cellularity, with or

without the accumulation of pigmented material), larynx (pigment accumulation within the

epithelium and lamina propria) and kidneys (increased tubular pigment). Observations within

the larynx and lungs were considered to reflect the accumulation of inhaled test article, with

attempted clearance by the local mononuclear-phagocyte system. Accompanying findings

within the local lymph nodes and kidneys were considered to represent the subsequent

systemic dissemination of test article. Findings were more pronounced, in terms of incidence

and severity, amongst animals dosed with 87.9 μg/L, and displayed a clear dose-related

response. Amongst animals dosed with 2.44 μg/L, findings were restricted to the lungs and

tracheobronchial lymph nodes

Conclusions:

NOAEC (systemic) 9.19 µg/LK
LOAEC (local) 2.44 µg/L (findings were restricted to the lungs and
tracheobronchial lymph nodes)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEC

9.19 ng/m³

Study duration:

subacute

Species:

rat

Repeated dose toxicity: inhalation - local effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

201/2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study, glp

Qualifier:

according to guideline

Guideline:

OECD Guideline 412 (Subacute Inhalation Toxicity: 28-Day Study)

Deviations:

not applicable

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: RccHanTM:WIST rats

Sex:

male/female

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Remarks on MMAD:

MMAD / GSD: 2.7 - 3.0 µm

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

4 weeks (6 hours per day, 5 days per week)

Frequency of treatment:

daily

Remarks:

Doses / Concentrations:
0 µg/L
Basis:
analytical conc.

Remarks:

Doses / Concentrations:
2.44 µg/L
Basis:
analytical conc.

Remarks:

Doses / Concentrations:
9.19 µg/L
Basis:
analytical conc.

Remarks:

Doses / Concentrations:
87.9 µg/L
Basis:
analytical conc.

No. of animals per sex per dose:

10

Control animals:

yes

Dose descriptor:

NOAEC

Remarks:

systemic

Effect level:

9.91 other: µg/L

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LOAEC

Remarks:

local

Effect level:

2.44 other: µg/L

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: findings were restricted to the lungs and tracheobronchial lymph nodes.

Critical effects observed:

not specified

Summary data are presented below:

Group Exposure level (μg/L) Particle size

Target Achieved MMAD (μm) sg

2 2.3 2.44 3.0 2.54

3 9.1 9.19 3.0 2.41

4 80 87.9 2.7 2.44

MMAD Mass median aerodynamic diameter

sg Geometric standard deviation

The achieved levels were 106, 101 and 110% of the target concentrations for Groups 2, 3 and

4 respectively. The Mass Median Aerodynamic Diameters for Groups 2, 3 and 4 are within

the ideal range (1-3 μm) for a repeat dose inhalation study.

There were no treatment related clinical signs observed during the detailed weekly physical

examination.

Lower body weight gain was evident for males exposed to 9.19 μg/L and 87.9 μg/L and for

all females exposed to tin monoxide. Food consumption was also slightly reduced for males

exposed to 87.9 μg/L.

A statistically significant increase in group mean activated partial thromboplastin times were

evident for males exposed to 9.19 and 87.9 μg/L and all females exposed to tin monoxide.

Group mean venous blood oxygen saturation levels were increased for females exposed to

9.19 μg/L and both sexes exposed to 87.9 μg/L.

Two hours after the completion of exposure in Week 4, tin was detected in the plasma of a

single male and female exposed to 9.19 μg/L and in all animals exposed to 87.9 μg/L. Tin

was not quantifiable in control animals or animals exposed to 2.44 μg/L.

Group mean lung and bronchi weights (adjusted for terminal body weight) were greater than

control for all animals exposed to tin monoxide.

Histopathological changes related to treatment were observed within the lungs (the

accumulation of pigmented and flocculent material within alveoli, variably accompanied by

both diffuse and local aggregations of alveolar macrophages, and increased cellularity of the

BALT), tracheobronchial and mediastinal lymph nodes (increased general cellularity, with or

without the accumulation of pigmented material), larynx (pigment accumulation within the

epithelium and lamina propria) and kidneys (increased tubular pigment). Observations within

the larynx and lungs were considered to reflect the accumulation of inhaled test article, with

attempted clearance by the local mononuclear-phagocyte system. Accompanying findings

within the local lymph nodes and kidneys were considered to represent the subsequent

systemic dissemination of test article. Findings were more pronounced, in terms of incidence

and severity, amongst animals dosed with 87.9 μg/L, and displayed a clear dose-related

response. Amongst animals dosed with 2.44 μg/L, findings were restricted to the lungs and

tracheobronchial lymph nodes

Conclusions:

NOAEC (systemic) 9.19 µg/LK
LOAEC (local) 2.44 µg/L (findings were restricted to the lungs and
tracheobronchial lymph nodes)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LOAEC

2.44 mg/m³

Study duration:

subacute

Species:

rat

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

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
SnO reachts in stomach with HCL to SnCl_2, no new study performed in due to animal protection.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Due to the low incidence and severity of findings for animals exposed to 9.19 μg/L, they
were considered to be non-adverse

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Amongst animals dosed with 2.44 μg/L, findings were restricted to the lungs and
tracheobronchial lymph nodes

Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: larynx; respiratory: trachea; urogenital: kidneys

Justification for classification or non-classification

Under consideration of Regulation (EC) 1272/2008 Annex 1 Section 3.9.2 and the outcome of above named OECD 412 study (NOAEL 9.19 µg SnO /L) it is required to classify the substance as STOT RE1 – H372.