Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
25 Jul - 08 Aug 1997
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
GLP - Guideline study, tested with the source substance Kaolin, calcined (CAS 92704-41-1). According to the ECHA guidance document “Practical guide 6: How to report read-across and categories (March 2010)”, the reliability was changed from RL1 to RL2 to reflect the fact that this study was conducted on a read-across substance.

Data source

Reference Type:
study report
Report Date:

Materials and methods

Test guideline
according to
EPA OPP 81-3 (Acute inhalation toxicity)
GLP compliance:
Test type:
fixed concentration procedure
Limit test:

Test material

Details on test material:
- Name of test material (as cited in study report): M-97-009
- PSL Code number E70704-3D
- Physical state / appearance: white powder
- Analytical purity: not stated
- Composition of test material, percentage of components: Calcined Kaolin - 100%
- Lot/batch No.: Lot #09255
- Expiration date of the lot/batch: none
- Stability under test conditions: stable
- Storage condition of test material: at room temperature
- Solubility: insoluble

Test animals

Details on test animals and environmental conditions:
- Strain: Sprague-Dawley derived, albino
- Source: Ace Animals, Inc., Boyertown, PA
- Age at study initiation: young adult
- Weight at study initiation: 226 - 238 grams (males) and 197 - 211 grams (females)
- Housing: singly housed in suspended stainless steel caging with mesh floors (which conform to the size recommendations in the Guide for the Care and Use of Laboratory Animals DHEW No. 86.23.
- Exposure chamber: Rectangular whole body perspex chamber with a volume of 100 liters operated under slight negative pressure
- Diet (e.g. ad libitum): Purina Rodent Chow #5012
- Water (e.g. ad libitum): Tap water (ad libitum)
- Acclimation period: 10 days
- Contaminants: Analyses of the food and water are conducted at least once a year

- Temperature: 16.1 - 23.9 °C; during exposure 21.1 - 22.8 °C
- Humidity: 55-60%
- Air changes (per hr):total air flow ranged from 50.2 - 50.8 Lpm
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
whole body
Details on inhalation exposure:
- Exposure apparatus: Exposure chamber, DF 183 Wright Dust Container, Carver Lab Press Model C, DF 191 Stainless Steel Cutting Blade, Dayton Model 4Z538Aadjustable speed motor
- Exposure chamber volume: 100 liters
- Source and rate of air: filtered air, air compressor JUN-AIR, Omega Mass Flowmeter Model #FMA 5613, total airflow ranged from 50.2 to 50.8 with a mean of 50.5 Lpm
- Method of conditioning air: Taylor Humidity-Temperature Indicator 5502, Dickson Temperature-Humidity Monitor Model TH550
- System of generating particulates/aerosols: test substance was packed into the DF 183 Wright Dust Container and compressed to 1750 lbs/in2 using a Carver Lab Press Model C. The container was then fitted with a DF 191 Stainless Steel Cutting Blade and driven by a Dayton Model 4Z538A adjustable speed motor. Compressed air was supplied to the dust generator at 30 psi. The aerosolized dust was then fed directly into the chamber through the dust outlet assembly.
- Method of particle size determination: An eight stage Andersen cascade impactor was used to assess the particle size distribution of the test atmosphere. Samples were withdrawn from the breathing zone of the animals at two intervals. The filter paper collection stages were weighed before and after sampling to determine the mass collected upon each stage. The aerodynamic mass median diameter and geometric standard deviation were determined graphically using two-cycle logarithmic probit axes.
- Temperature, humidity, pressure in air chamber: slight negative pressure, 70-73° F (21,1-22.8° C), 55-60% RH

- Brief description of analytical method used: 25 mm glass fiber filters (GF/B Whatman) in a fliter holder attached by 1/4 inch tygon tubing to a General Electric vacuum pump Model 5KH10GGR28; filter papers were weighed; collections were carried out for 2 minutes at airflow of 4 Lpm; Omega Mass Flowmeter Model #FMA 5610
- Samples taken from breathing zone: yes

-approx. 670 grams of the test substance was processed in a urethane-lined milling jar (1.6 gallon Abbethane, Paul O'Abbe) with porcelain grinding media (0.5" balls) for 24 hours. After milling, the substance was sieved through a 3/8" polyethylene sieve to separate it from the grinding media and any other large particles which remained.

TEST ATMOSPHERE is tabulated

- MMAD (Mass median aerodynamic diameter): <= 4 µm ( estimated to be 2.5 microns)
Analytical verification of test atmosphere concentrations:
gravimetric samples were withdrawn at six intervals from the breathing zone of the animals
Duration of exposure:
4 h
Remarks on duration:
and 9 minutes (time for equilibration (T99)
ca. 2.0 mg/L (gravimetric and nominal concentrations were 2.07 and 10.77 mg/L)
No. of animals per sex per dose:
Control animals:
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: bodyweights were recorded prior to exposure and again on days 7 and 14; the animals were observed for signs of gross toxicity and behavioral changes prior to exposure, at least every 30 minutes for the first 2.5 hours during exposure, upon removal from the exposure chamber and at least once daily thereafter for 14 days; additional in-chamber animal observations were limited due to the accumulation of the test substance on the walls of the exposure chamber
- Necropsy of survivors performed: yes
- Other examinations performed:Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Results and discussion

Effect levels
Dose descriptor:
Effect level:
> 2.07 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: 4 h and 9 min
no mortality
Clinical signs:
During the initial 2.5 hours of exposure: ocular discharge (clear, two males, one female), nasal discharge (clear, ten animals), test substance on fur (ten animals), hunched posture (one male).
All rats recovered from these symptoms within 17 hours and appeared active and healthy for the remainder of the study.
Body weight:
gained weight
Gross pathology:
moderately red lungs (two males, four females) and dark red foci present in one female lung
customarily seen with CO2 inhalation, euthanasia procedure;
all other tissues and organs appeared normal

Applicant's summary and conclusion