Chrome tin orchid cassiterite

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 5000 mg/kg bw (nominal) (OECD 423; GLP compliant)

Acute inhalation toxicity: LC50 > 5.06 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:

2021-08-24 to 2021-09-08

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:

2001-12-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

GLP certificate signed 2020-03-05.

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: room temperature (15-25 ºC, below 70 RH%), protected from light.

Species:

rat

Strain:

Wistar

Remarks:

Han

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt., H-1122 Budapest, Magyar Jakobinusok tere 4B
- Females nulliparous and non-pregnant: yes
- Age at study initiation: approx. 9 - 10 weeks
- Weight at study initiation: 191 - 194 g
- Fasting period before study: yes, overnight.
- Housing: animals were housed individually (1st treated animal) or in
group (2 animals/cage) in T3H polycarbonate cages; wooden chips: “SAFE 3/4-S-FASERN” certified, (J. Rettenmaier & Söhne GmbH & Co.KG, Rosenberg, Germany); nest material: “Sizzle pet” (LBS (Serving Biotechnology) Ltd., Hookwood, Surrey, United Kingdom).
- Diet (ad libitum): standard laboratory rat diet, SM Rat/Mouse, Breeding & Maintenance, 10 mm, autoclavable (manufacturer: ssniff Spezialdiäten GmbH, Soest, Germany)
- Water (ad libitum): tap water
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature: 21 – 23 °C
- Humidity: 39 – 58 %
- Air changes (per hr): 15 - 20
- Photoperiod (hrs dark / hrs light): 12 / 12, from 6.00 a.m. to 6.00 p.m.

Route of administration:

oral: gavage

Vehicle:

methylcellulose

Remarks:

in distilled water (1 % solution)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 500 mg/mL
- Justification for choice of vehicle: The selection of the vehicle was made during trial formulations with the test item.
- batch no.: 2005-4320

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION:
The test item was freshly formulated in the vehicle at the appropriate concentration on the day of administration. The formulations were stirred with magnetic stirrer up to finishing the treatment.

CLASS METHOD
- Rationale for the selection of the starting dose: a starting dose level of 5000 mg/kg bw was selected for the following reasons: the study will be used for EU countries implementing CLP regulation as well as for non-EU countries implementing GHS regulation. Furthermore, the test item is a complex inorganic salt which shows low water solubility. As the bioavailability (and thus solubility) of the test item is a key determinant of toxicity, low toxicity was expected, therefore justifying an initial testing at the limit dose of 5000 mg/kg bw.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: following the end of the dosage, the animals were observed individually for clinical signs once during the first 30 min., at 1, 2, 3, 4 and 6 hours after the treatment and once daily.
Body weight of the animals was recorded on days 0 (prior to dosing), 7 and 14 (prior to necropsy).
- Necropsy of survivors performed: yes, on day 14, all animals were sacrificed, and subjected to a necropsy and a macroscopic examination.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Preliminary study:

Not applicable

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

No death occured.

Clinical signs:

other: All animals were symptom-free during the 14-day observation period at a dose level of 5000 mg/kg bw. Purple coloured faeces were observed in the bedding on Day 1, which is test item related.

Body weight:

other body weight observations

Remarks:

There were no effects on body weight or body weight gain that could be attributed to treatment with the test item.

Gross pathology:

There were no macroscopic changes seen at necropsy.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (female rats) > 5000 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

Quality of whole database:

The study fulfils the rquirements for acute oral toxicity under REACH (Regulation (EC) 1907/2006).

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 2015-08-24

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

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. 10 weeks
- Weight at study initiation: males: 272 - 333 g; females: 244 - 258 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):

>= 2.079 - <= 2.159 µm

Geometric standard deviation (GSD):

>= 2.36 - <= 2.56

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 (20.8°C ± 0.1°C (main study) or 20.5°C ± 0.2°C (satellite group)) and humidity (57.4% ± 0.1% (main study) or 55.6% ± 0.1% (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: 2.079 µm (GSD: 2.56)
Satellite group: 2.159 µm (GSD: 2.36)

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: 5.06 ± 0.01 mg/L air
- nominal concentration: 55.56 mg/L air
Satellite group:
- actual concentration: 5.05 ± 0.01 mg/L air
- nominal concentration: 55.56 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 3, 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:

> 5.06 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

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

Clinical signs:

other: please refer to other findings

Body weight:

5.06 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:

Clinical signs
5.06 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 exposure, but not necessarily test item-related).
5.05 mg/L air (satellite group): slight dyspnoea until 3 hours post exposure in all male and female animals, respectively

Microscopic changes in the lungs
The histomorphological examination of rat lungs from a acute inhalation toxicity study of Chrome Tin Orchid Cassiterite (Pigment Red 236) 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) > 5.06 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 EC-Regulation 1272/2008 and subsequent regulations, the test item 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 reliable study described in Kiss (2021; OECD 423 (2001); GLP compliant) is considered to be reliable without restrictions and used as key study for this endpoint. The LD50 was determined to be greater than 5000 mg/kg bw (nominal concentration).

 

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 5.06 mg/L air (actual concentration).

Justification for classification or non-classification

Acute oral toxicity

The available guideline-conform study conducted under GLP indicate that test item is not acutely toxic via the oral 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: oral

The classification criteria acc. to regulation (EC) 1272/2008 as specific target organ toxicant (STOT) - single oral 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 of 300 mg/kg bw and at the guidance value, oral for a Category 2 classification of 2000 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.