Tin antimony grey cassiterite

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (OECD 423; GLP compliant)

Acute inhalation toxicity: LC50 > 5.07 mg/L air (analytical) (OECD 436; GLP compliant)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2000-02-29 to 2000-03-16

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Version / remarks:

1996-03-22

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: males: 340 - 425 g; females: 208 - 225 g
- Fasting period before study: food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3 - 4 hours after administration of the test substance
- Housing: group housing of 3 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material (SAWI, Jelu Werk, Rosenberg,Germany).
- Diet (ad libitum): standard pelleted laboratory animal diet (from Cerfil Quality BVBA, Oud-Turnhout, Belgium)
- Water (ad libitum): tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21°C
- Relative humidity: 30 - 70%
- Air changes: approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: vehicle was selected based on a pretest performed

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION:
The formulation (w/w) was prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of vehicle (specific gravity 1.036).

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 males / 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: mortality/viability was recorded twice daily; body weights were recorded on days 1 (pre-administration), 8 and 15; clinical signs at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15
- Necropsy of survivors performed: yes, at the end of the observation period

Statistics:

No statistical analysis was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: - females: hunched posture, uncoordinated movements and/or piloerection - males: lethargy and/or uncoordinated movements The animals had recovered from the symptoms between days 2 and 4.

Gross pathology:

No abnormalites were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (male and female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance is not acutely toxic via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-07-30 to 2015-08-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 436 (Acute Inhalation Toxicity: Acute Toxic Class Method)

Version / remarks:

2009-09-07

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2014-05-14

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: kept dry in closed container at room temperature

Species:

rat

Strain:

other: Crl: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: males: approx. 8 weeks; females: approx. 9 weeks
- Weight at study initiation: males: 230 - 262 g; females: 222 - 240 g
- Fasting period before study: approx. 16 hours before exposure; only tap water was then available ad libitum
- Housing: during the 14-day observation period, the animals were kept by sex in groups of 2 - 3 animals in MAKROLON cages (type III plus); granulated textured wood (Granulat A2, J. Brandenburg, 49424 Goldenstedt, Germany) was used as bedding material for the cages.
- Diet: commercial diet, ssniff® R/M-H V1534 (ssniff Spezialdiäten GmbH, 59494 Soest, Germany)
- Water (ad libitum): drinking water
- Acclimation period: at least 5 adaptation days

ENVIRONMENTAL CONDITIONS
- Temperature: 22°C ± 3°C (maximum range)
- Relative humidity: 55% ± 15% (maximum range)
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

>= 2.215 - <= 2.298 µm

Geometric standard deviation (GSD):

>= 2.23 - <= 2.34

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: the study was carried out using a dynamic inhalation apparatus (RHEMA-LABORTECHNIK, 65719 Hofheim/Taunus, Germany) (air changes/h (≥ 12 times)) with a nose-only exposure of the animals according to KIMMERLE & TEPPER. The apparatus consists of a cylindrical exposure chamber (inner diameter: 28.2 cm; height: 64.6 cm; volume 40.3 L) which holds the animals in pyrex tubes at the edge of the chamber in a radial position.

- System of generating particulates/aerosols: the dust of the test material was generated with a rotating brush dust generator (RBG 1000, PALAS GmbH Partikel und Lasermesstechnik, 76229 Karlsruhe, Germany).
The generator was fed with compressed air (5.0 bar) from a compressor (ALUP Kompressorenfabrik, 73257 Köngen, Germany).
At the bottom of the exposure chamber, the air was sucked off at a lower flow rate than it was created by the dust generator in order to produce a homogenous distribution and a positive pressure in the exposure chamber (inflow 900 L/h, outflow 800 L/h).
A manometer and an air-flow meter (ROTA Yokogawa GmbH & Co. KG, 79664 Wehr/Baden, Germany) were used to control the constant supply of compressed air and the exhaust, respectively. Flow rates were checked hourly and corrected if necessary.
The exhaust air was drawn through gas wash-bottles.

- Method of particle size determination: an analysis of the particle size distribution was carried out twice during the exposure period using a cascade impactor (Cascade impactor 6.0 L/min (Article No. 700800-CI-060), TSE Systems GmbH, 61352 Bad Homburg, Germany).
The dust from the exposure chamber was drawn through the cascade impactor for 1 minute at a constant flow rate of 5 L/min. The slides were removed from the impactor and weighed on an analytical balance (SARTORIUS, type 1601 004, precision 0.1 mg). Deltas of slides’ weight were determined.
The mass median aerodynamic diameter (MMAD) was estimated by means of non-linear regression analysis. The 10.6 µm particle size range and the filter (particle size range < 0.55 µm) were not included in the determination of the MMAD in order not to give undue weight to these values.
The Geometric Standard Deviation (GSD) of the MMAD was calculated from the quotient of the 84.1%- and the 50%-mass fractions, both obtained from the above mentioned non-linear regression analysis.
In addition, a sample of approx. 10 g test material was taken from the exposure chamber to determine the median physical particle size with a Malvern Mastersizer 2000 by My-Tec, 91325 Adelsdorf, Germany. This determination was non-GLP.

- Temperature, humidity, pressure in air chamber, oxygen content and carbon dioxide content: the oxygen content in the inhalation chamber was 21%. It was determined at the beginning and at the end of the exposure with a DRÄGER Oxygen-analysis test set (DRÄGER Tube Oxygen 67 28 081). Carbon dioxide concentration did not exceed 1%.
Temperature (22.4°C ± 0.1°C (main study) or 21.8°C ± 0.1°C (satellite group)) and humidity (56.9% ± 0.2% (main study) or 59.9% ± 0.2% (satellite group)) were measured once every hour with a climate control monitor (testo 175-HZ data logger).

Exposition started by locating the animals into the exposure chamber after equilibration of the chamber concentration for at least 15 minutes (t95 approximately 8 minutes).

Before initiating the study with the animals, a pre-test was carried out with the exposure system in order to verify that under the experimental settings chosen, the limit concentration of 5 mg/L air could be achieved by gravimetric analysis.

TEST ATMOSPHERE
- Brief description of analytical method used: the actual dust concentration in the inhalation chamber was measured gravimetrically with an air sample filter (Minisart SM 17598 0.45 µm) and pump (Vacuubrand, MZ 2C (Membrane Pump, Vacuubrand GmbH + Co. KG, 97877 Wertheim/Main, Germany)) controlled by a rotameter. Dust samples were taken once every hour during the exposure. For that purpose, a probe was placed close to the animals' noses and air was drawn through the air sample filter at a constant flow of air of 5 L/min for 1 minute. The filters were weighed before and after sampling (accuracy 0.1 mg).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):
Main study: 2.215 µm (GSD: 2.34)
Satellite group: 2.298 µm (GSD: 2.23)

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above ("Details on inhalation exposure")

Duration of exposure:

4 h

Concentrations:

Main study (limit test):
- actual concentration: 5.07 ± 0.01 mg/L air
- nominal concentration: 44.44 mg/L air
Satellite group:
- actual concentration: 5.06 ± 0.02 mg/L air
- nominal concentration: 44.44 mg/L air

No. of animals per sex per dose:

Main study (limit test):
3 males / 3 females
Satellite group:
3 males / 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 24 hours (satellite group) and 14 days (main study)
- Frequency of observations and weighing: during and following exposure, observations were made. Clinical examinations were made at least once daily until all symptoms subsided, thereafter each working day. Observations on mortality were made at least once daily with appropriate actions taken to minimize loss of animals to the study (e.g. necropsy).
Individual weights of animals were determined once during the acclimatisation period, before the exposure on test day 1, on test days 2, 4, 8 and 15. Changes in weight were calculated and recorded when survival exceeded one day. At the end of the test, all animals were weighed and sacrificed.
- Necropsy of survivors performed: yes
Necropsy of all animals was carried out and all gross pathological changes were recorded for each animal with particular attention to any changes in the respiratory tract.
- Satellite animals: necropsy at 24 hours after cessation of exposure, as this is likely to be the time at which any signs of respiratory irritation would have manifested themselves;
- Main study animals: necropsy at the end of the 14-day observation period
.

Statistics:

Since no animal died prematurely, the calculation of an LC50 was not required.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.07 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

5.07 mg/L air (main study): no animal died prematurely.
5.06 mg/L air (satellite group): no animal died prematurely.

Clinical signs:

other: 5.07 mg/L air (main study): slight dyspnoea (reduced frequency of respiration with increased volume) until 3 hours post exposure in all male and female animals, respectively (considered to be an overall clinical sign of general toxicity common to dust exp

Body weight:

5.07 mg/L air (main study): no influence in body weight gain was noted.

Gross pathology:

Marbled and/or oedematous lungs were observed at necropsy in all main study and satellite animals.

Other findings:

Microscopic changes in the lungs
The histomorphological examination of rat lungs from an acute inhalation toxicity study of Tin Antimony Grey Cassiterte (Pigment Black 23) did not reveal any findings, which are considered to be related to the administration of the test item, neither in the main study nor in the satellite rats. The congestion in all animals correlated with the macroscopical finding pulmonary oedema and are regarded to represent agonal changes. The alveolar haemorrhages were interpreted as coincidental findings.

Interpretation of results:

GHS criteria not met

Conclusions:

LC50 (rats; 4 hours) > 5.07 mg/L air (actual concentration)
No respiratory irritant effects, other reversible functional impairments or toxic effects were observed in the satellite as well as in the main study animals.
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the substance does not require classification for acute inhalation toxicity and
specific target organ toxicity – single exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

One relibale (Klimisch 1) study report according to OECD 423 is available and is used as key study. The LD50 value was determined to be > 2000 mg/kg bw.

Acute inhalation toxicity

One reliable study described in Haferkorn (2017; OECD 436 (2009); GLP compliant) is considered to be reliable without restrictions and is used as key study for this endpoint. The LC50 was determined to be greater than 5.07 mg/L air (actual concentration).

Justification for classification or non-classification

Acute oral toxicity

The substance is not acutely toxic via the oral route based on an acute oral toxicity test (OECD 423) and does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.

Specific target organ toxicant (STOT) - single exposure: oral

The classification criteria according to Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value, oral for a Category 1 classification (C≤ 300 mg/kg bw) and at the guidance value, oral for a Category 2 classification (2000 mg/kg bw ≥ C > 300 mg/kg bw). No classification required.

Acute inhalation toxicity

The available guideline-conform study conducted under GLP indicate that test item is not acutely toxic via the inhalation route. Thus, according to Regulation (EC) No 1272/2008 and subsequent regulations, no classification or labelling is required.

Specific target organ toxicant (STOT) – single exposure: inhalation

The available guideline-conform study conducted under GLP indicate that the test item has no respiratory irritant effects, other reversible functional impairments or toxic effects.Thus, according to Regulation (EC) No 1272/2008 and subsequent regulations, no classification or labelling is required.