Tin monoxide

Repeated dose toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

not applicable

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Tin monoxide

EC Number:

244-499-5

EC Name:

Tin monoxide

Cas Number:

21651-19-4

Molecular formula:

OSn

IUPAC Name:

Tin monoxide

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: RccHanTM:WIST rats

Sex:

male/female

Administration / exposure

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

Doses / concentrations

Doses / concentrations 1

Remarks:

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

Doses / concentrations 2

Remarks:

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

Doses / concentrations 3

Remarks:

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

Doses / concentrations 4

Remarks:

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

No. of animals per sex per dose:

10

Control animals:

yes

Results and discussion

Effect levels

1

Dose descriptor:

NOAEC

Remarks:

systemic

Effect level:

9.91 other: µg/L

Based on:

test mat.

Sex:

male/female

2

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.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

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

Applicant's summary and conclusion

Conclusions:

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