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

Acute Toxicity: inhalation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(2009)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Version / remarks:

(1998)

Deviations:

no

Test guideline 4

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

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Details on test material:

- Appearance: White powder

Specific details on test material used for the study:

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

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels

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.

Any other information on results incl. tables

- 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%.

 

Applicant's summary and conclusion

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).