Calcination products of BaCO3, SrCO3, MgO, Al2O3, Eu2O3 and MnCO3

Endpoint summary

Description of key information

The acute oral and the acute inhalation toxicity of the substance have been determined. No mortality occurred. Based on the results of these studies, the substance is not classified for acute toxicity by the oral and the inhalation route.

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:

22 September 2015 - 08 October 2015

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)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- pH (1% in water, indicative range): 6.2 - 6.5
- Insoluble in water

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8-11 weeks old)
- Weight at study initiation: 186-206 g (1st group) and 155-159 g (2nd group)
- Fasting period before study: Animals were deprived of food overnight prior to dosing
- Housing: Group housing of 3 animals per cage in labeled Macrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (set conditions)
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 September 2015 To: 08 October 2015

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

(Elix, Millipore S.A.S., Molsheim, France)

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE
- The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw (10 mL/kg bw)

DOSAGE PREPARATION
The preparations (w/w) were dosed within 4 hours after adding the vehicle to the test item. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies. No correction was made for purity of the test item.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 (2 groups of three females in a stepwise manner)

Control animals:

no

Details on study design:

Animals were deprived of food until 3-4 hours after administration of the test substance.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: 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: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none

Statistics:

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

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality occurred.

Mortality:

No mortality occurred.

Clinical signs:

Hunched posture, piloerection and/or uncoordinated movements were noted for the animals on Day 1.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Gross pathology:

- No test substance related abnormalities were found.
- Pelvic dilatation of the right kidney was found in one animal. Since this is occasionally seen among rats of this age and strain and it was found in one animal only, this was considered not toxicologically significant.

Interpretation of results:

other: the substance does not need to be classified for acute toxicity by the oral route according to GHS and CLP

Conclusions:

In an acute oral toxicity study in rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

Executive summary:

The acute oral toxicity of the substance was determined in accordance with OECD 423 (2001) and according to GLP principles. The substance was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. No mortality occurred. Hunched posture, piloerection and/or uncoordinated movements were noted for the animals on Day 1. Necropsy did not show any abnormality. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight. Based on the results of this study, the substance does not need to be classified for acute toxicity by the oral route according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP Regulation).

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:

18 March 2016 - 04 April 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(2009)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Version / remarks:

(2008)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

(1998)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000; including the most recent partial revisions

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

- pH (1% in water, indicative range): 6.5-6.2

Species:

rat

Strain:

other: Crl:WI(Han)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: appr. 9 weeks
- Weight at study initiation: 243-272 g (males); 170-192 g (females)
- Fasting period before study: no
- Housing: Group housing of five animals per sex per cage in labeled Makrolon cages
- Diet: pelleted rodent diet (SM R/M-Z from SNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum (no access to food during exposure)
- Water: tap water, ad libitum (no access to water during exposure)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS (set conditions)
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: March 18, 2016 To: April 4, 2016

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: based on the flow past nose-only inhalation chamber (Am. Ind. Hyg Assoc. J. 44(12): 923-928, 1983)
- Method of holding animals in test chamber: restraining tubes
- Exposure chamber volume: ca. 150 mL
- Rate of air: at least 1 L/min (theoretical air flow in each animal port); mean total airflow: 15 L/min
- System of generating particulates/aerosols: administering the test item to a stream of pressurized air was performed using a combination of a spiral feeder and an air mover. The aerosol was passed through a series of four cyclones, allowing larger particles to settle, before it entered the exposure chamber.
- Method of particle size determination: The particle size distribution was characterized twice during the exposure period. The samples were collected with an 8 stage Marple personal cascade impactor containing fiber glass filters and a fiber glass back-up filter. Amounts of test item collected were measured gravimetrically.
- Treatment of exhaust air: filtered and released to the exhaust of the fume hood
- Temperature, humidity in air chamber: 20.6-21.4°C; 26-31%

TEST ATMOSPHERE
- Brief description of analytical method used: The collected amount of the test item in the air sample was measured gravimetrically. Sample volumes were measured by means of a dry gas meter. The time-weighted mean concentration with the standard deviation was calculated.
- Samples taken from breathing zone: yes, a total of 25 samples was taken during exposure.

TEST ATMOSPHERE
- MMAD (Mass median aerodynamic diameter): 3.5 µm (GSD (Geometric st. dev.): 1.8) and 3.5 µm (GSD: 1.9)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Technically maximum attainable concentration (3.5 ± 0.06 mg/L)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- The test atmosphere generation was based on the method developed during extensive trial generations. During the trials it was determined that the study could not be performed at a constant test atmosphere concentration of at least 5 mg/L. The generation was therefore performed at the technically maximum attainable concentration.
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Three times during exposure (mortality, signs of distress and effects on respiration); after exposure twice daily for mortality and clinical signs were observed one and three hours after exposure (day 1), and once daily thereafter. Body weight determined on days 1 (pre-administration), 2, 4, 8 and 15.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: LC50: >technically maximum attainable concentration (3.5 mg/L)

Mortality:

No mortality occurred.

Clinical signs:

other: - During exposure, shallow breathing was seen in one animal - After exposure, no clinical signs were noted

Body weight:

Overall body weight gain in males and females was within the range expected for rats of this strain and age used in this type of study.

Gross pathology:

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

Other findings:

Grey staining of the head by test item remnants was seen for all animals on Day 1.

- The time-weighted mean actual concentration was 3.5 ± 0.06 mg/L. The concentration was measured at time points (n=25) that were equally distributed over the exposure period, the results of which demonstrated that the item was sufficiently stable.

- The nominal concentration (amount of test item used divided by the volume of pressurized air used) was 219 mg/L. The generation efficiency (ratio of actual and nominal concentration) was 1.6%.

 

Interpretation of results:

other: the substance does not need to be classified for acute toxicity by the inhalation route according to GHS and CLP

Conclusions:

In an acute inhalation toxicity study with male and female rats, performed according OECD test guideline and GLP principles, an LC50 above the technically maximum attainable concentration was determined for the substance.

Executive summary:

An acute inhalation toxicity study with nose-only exposure was performed according to OECD 403 and GLP principles. Based on the method developed during extensive trial generations, the test atmosphere generation was performed at the technically maximum attainable concentration. Five animals of each sex were exposed in a limit test for 4 hours to the technically maximum attainable concentration. The MMAD was determined to be 3.5 µm, while the concentration was measured to be 3.5 ± 0.06 mg/L. No mortality occurred. During exposure, shallow breathing was seen in one animal. After exposure, no clinical signs were noted. The LC50 was concluded to be above the technically maximum attainable concentration (>3.5 mg/L). Based on the results of this study, the substance is not classified for acute toxicity by the inhalation route according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP Regulation).

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

The acute oral toxicity of the substance was determined in accordance with OECD 423 (2001) and according to GLP principles. The substance was administered by oral gavage to two subsequent groups of three female Wistar rats at 2000 mg/kg body weight. No mortality occurred. Hunched posture, piloerection and/or uncoordinated movements were noted for the animals on Day 1. Necropsy did not show any abnormality. The acute oral toxicity (LD50) was determined to be >2000 mg/kg bw. According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Acute inhalation toxicity

An acute inhalation toxicity study with nose-only exposure was performed according to OECD 403 and GLP principles. Based on the method developed during extensive trial generations, the test atmosphere generation was performed at the technically maximum attainable concentration. Five animals of each sex were exposed in a limit test for 4 hours to the technically maximum attainable concentration. The MMAD was determined to be 3.5 µm, while the concentration was measured to be 3.5 ± 0.06 mg/L. No mortality occurred. During exposure, shallow breathing was seen in one animal. After exposure, no clinical signs were noted. The LC50 was concluded to be above the technically maximum attainable concentration (>3.5 mg/L).

Justification for classification or non-classification

Based on the results of the acute oral toxicity study and the acute inhalation toxicity study, the substance is not classified for acute toxicity by the oral and the inhalation route according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Regulation (EC) No 1272/2008 (CLP Regulation).