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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990-08-15 until 1990-09-05
Reliability:
1 (reliable without restriction)
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report date:
1990

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted: 1981-05-12
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
, dated: 1984-09-19
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: Environmental Protection Agency- Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation: "Human and Domestic Animals", Paragraph 81-3 "Acute Inhalation Toxicity Study", November 1982, Revised Edition, November 1984.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Disodium disilicate
EC Number:
237-623-4
EC Name:
Disodium disilicate
Cas Number:
13870-28-5
Molecular formula:
Na2Si2O5
IUPAC Name:
disodium disilicate
Details on test material:
- Name of test material (as cited in study report): SKS 6, Natriumschichtsilikat, kristallin
- Physical state and appearance: White solid
- Analytical purity: > 98%
- Storage condition of test material: At room temperature (20°C), in a closed container.
- Safety precautions: Gloves, goggles and face mask were sufficient to assure personnel health and safety handling of the test substance. The face mask was replaced by a full face respirator with positive, filtered (A2-P3) air supply during administration.


Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BRL, Biological Research Laboratories Ltd. CH-4414 Fuellinsdorf, Switzerland.
- Age at delivery: Males: 8-10 weeks, females: 10-12 weeks
- Weight at study initiation: Males mean weight: 221.5 g and females mean weight: 195.4 g
- Housing: Animals were housed in groups of five in Makrolon type- 4 cages with standard softwood bedding ("Lignocel", Schill AG, CH-4132 Muttenz, Switzerland).
- Diet: Pelleted standard liba 343, Batch Nos. 70/90 and 73/90 rat maintenance diet ("Kliba", Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland), ad libitum
- Water: Tap water, ad libitum.
- Acclimation period: 6 days under laboratory conditions after clinical health examination.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3°C
- Humidity (%): 30- 70%
- Air changes (per hr): 10-15 air changes per hour.
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours dark period.


IN-LIFE DATES: From: 1990-08-09 To: 1990-09-05

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus, exposure chamber volume: Inhalation, according to the method of Sachsse et al. (1973, 1976). The animals are confined separately in tubes which are positioned radially around the exposure chamber. The test article stream reaches the animal´s nose through ports situated at different levels around the axis of the exposure chamber. The internal active volume of the chamber for exposing 40 animals by nose-only is one liter. The resulting time for the concentration at an animal port to reach 99% of its ultimate value (T99) is 34 seconds for the 40 animal chambers. The system is constructed of anodised aluminium and readily accepts a variety of different sized makrolon animal restraint tubes which have been designed in consideration of the anatomy and physiology of the rodent.

- Source and rate of air: The airflow rate through the impactor (see below in "particle size determination") was 1.0 L/min.

- System of generating particulates/aerosols: The test article atmosphere was generated by using two aerosol generators (RBG- 1000 Palas, Germany) equiped with a Brush-feed Micronising Jet Mill discharged into the exposure chamber.

- Method of particle size determination: The particle size of the test atmosphere was determined using a Mercer 7 stage cascade impactor (Model 02-1300, In-Tox Inc., Albuquerque, New Mexico, U.S.A). The test atmosphere was impacted at each stage onto stainless steel slips which were weighed before and after sampling using a Model M3 balance (Mettler AG, Switzerland). The determination of particle size distribution was performed twice during exposure.

- Treatment of exhaust air: The study´s system provides a constant stream of "fresh" test article to each animal, and precludes rebreathing of the exhaled air. The test atmosphere is delivered through tubes to the animal´s nose and is then extracted away through a second concentric tube which is maintained under negative pressure through aspiration at the outlet.

- Temperature, humidity, oxygen concentration: Temperature: 21.0°C, relative humidity: 22.5% , oxygen concentration: 20.9 vol%.


TEST ATMOSPHERE
- Brief description of analytical method used: Concentration, particle size distribution, oxygen concentration, relative humidity and temperature were measured on test atmosphere samples taken at the site of the animal´s snout in the exposure system. All measurments were taken directly from the test atmosphere feed tube on the flow-past exposure system which delivers fresh test article to the animal´s nose. Thus, all sampling was isoaxial and represented exactly what was delivered to the animal´s nose.
The test substance (in a gravimetric determination of concentration) was sampled from the exposure unit as described above, was collected on Gelman A/E 47 mm diameter glass fiber filters using a stainless steel filter sampling device (Gelman Science Inc., Ann Arbor, Michigan, U.S.A). The relative aerosol concentration was monitored using a RAM-1 light scattering type aerosol monitor (GCA Corp., bedford, Massachussetts, U.S.A). Nine gravimetric determinations were performed during exposure.

- Samples taken from breathing zone: yes


TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: 36.1% (mean) ≤ 3 µm
- MMAD (Mass median aerodynamic diameter): The study´s aerosols generating system (see above) was used in order to achieve the required concentrations with a mass median aerodynamic diameter of 3 µm or less.


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
The mean concentration was 3.51 mg/L air (highest technically achievable concentration).
No. of animals per sex per dose:
5 animals per sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: 22 days
- Frequency of observations and weighing: Mortality: Once per hour during exposure, once after exposure on test day 1, and two times daily thereafter. Body weights: On day 1 (before exposure), 8, 15 and 22 of test day. Clinical signs: Once per hour during exposure, once after exposure and at least once daily thereafter.
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs, body weight, organ weights and necropsy for identifying macroscopic changes or abnormalities
Statistics:
The LOGIT- Model could not be applied to the observed rates of death (only one female animal died on day 9). The toxicity was estimated without the use of a statistical model.

Results and discussion

Preliminary study:
Not indicated.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 3.51 mg/L air
Exp. duration:
4 h
Mortality:
One female rat died on the 9th test-day.
Clinical signs:
other: All animals were restless during exposure. Several clinical signs were observed during the three-week observation period: hunched posture, labored respiration, rales and ruffled fur; mild to severe necrosis, wounds or sore spots located on the nose, snout
Body weight:
Most animals lost weight during the first week of observation (on the average 15 g for the males and 37.5 g for the females). All males except for one and all females regained weight thereafter. On test-day 22, the mean body weight of the four surviving females was still slightly less than on test-day 1.
Gross pathology:
External observations included: sores on the nose region of 1 male and 3 females, on the forefoot of one female and also alopecia on the cervical region of one female.
The lungs of three males and two females were either not, or incompletely collapsed. Many dark red foci were seen on the lungs of one female. The digestive tract of one male and one female was distended with gas.
Other findings:
No other findings.

Any other information on results incl. tables

No remarks

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information: . See in "Justification for classification or non-classification" in the Acute Toxicity endpoint summary.
Conclusions:
LC50> 3.51 mg/L air
Executive summary:

In the acute inhalation toxicity study (study no.: 272406) 5 male and 5 female Wistar rats (males: 8-10 weeks old, mean weight, 221.5 g and females: 10-12 weeks, mean weight, 195.4 g) were exposed for 4 hours to disodium disilicate (delta-crystalline) by a single administration to a mean concentration of 3.51 mg/L air (corresponding to 3510 mg/m³ air) of the test substance (the highest technically achievable concentration) via the inhalation route (nose only, aerosols). Following the exposure period the animals were observed for 22 days for clinical signs, body weights and mortality. All animals were necropsied and subjected to gross macroscopic examination. One female rat died on test-day 9. Several clinical signs were observed during the three-week observation period and some gross pathology findings were found in the macroscopic observations after necropsy (which should be re-examined for substance-related effects in a subchronic assay). In this acute 4-hour inhalation toxicity study a LC50 greater than 3.51 mg/L air (corresponding to 3510 mg/m³ air) was estimated for male and female rats.

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