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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
04.01.2007 to 10.05.2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to an appropriate OECD test guideline, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Trimethylsilanol - Substance type: Alkylsilane - Physical state: Liquid - Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS- Source: Charles River Laboratories - Age at study initiation: Nine weeks. - Weight at study initiation: 310 g to 346 g for males and from 207 g to 242 g for females - Fasting period before study: No - Housing: Individual suspended wire-mesh cages. - Diet (e.g. ad libitum): Ad libitum except during exposure. - Water (e.g. ad libitum): Ad libitum except during exposure. - Acclimation period: Seven days. ENVIRONMENTAL CONDITIONS- Temperature (°C): 22 ± 3°C - Humidity (%): 50 ± 20% - Air changes (per hr): 12-15 - Photoperiod (hrs dark / hrs light): 12/12 IN-LIFE DATES: From: 22.01.2007 To: 13.02.2007

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION- Exposure apparatus: On the day of exposure, the animals were placed in wire mesh batteries containing separate cages, transported to the exposure room, exposed for the requisite duration then returned to their home cages. - Exposure chamber volume: 6 × 4 × 8 inches - Source and rate of air: 12-15 changes per hour - System of generating vapour: The test article was metered at a known flow rate by a liquid metering pump to the top of a glass bead vaporization column filled with 3-, 6-, 12- and 16-mm glass beads. The bead column and delivery line were wrapped with an electric heating tape controlled using a J-type thermocouple and digital temperature controller set at 100°C and 118°C, respectively. Nitrogen was metered to the bottom of the vaporization column using a regulator and a Gilmont rotameter-type flowmeter. Vaporization occurred as the liquid test article coated the surface of the heated beads and nitrogen flowed up through the column. The test article vapors were piped to the chamber inlet where the concentration was reduced to the desired concentration by mixing with the chamber supply air. The exhaust atmosphere passed through the in-house exhaust system before being released from the facility. - Temperature, humidity, pressure in air chamber: as above. TEST ATMOSPHERE- Brief description of analytical method used: Analyzed exposure concentrations were determined at approximately 30-minute intervalsusing a gas chromatograph (GC). - Samples taken from breathing zone: not specified. CLASS METHOD (if applicable)- Rationale for the selection of the starting concentration: The target exposure concentration for the limit test was based on the recommended safe working level of one-half of the lower explosion limit (LEL). Given the vapor pressure and LEL of the test article (1.45 volume % in air), the target limit test exposure concentration was 7250 ppm. The target exposure concentration for exposures 2 and 3 were provided by the sponsor/study director based on the results of the previous exposure(s).
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
ca. 4 h
Concentrations:
1976, 3668 and 7602 ppm (actual exposure concentrations 1824, 3517 and 7443 ppm)
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: Each animal was observed for mortality at the approximate midpoint of exposure, immediately following exposure on study day 0 and twice daily thereafter for 14 days. - Necropsy of survivors performed: yes - Other examinations performed: Each animal was observed for clinical observations immediately following exposure on study day 0 and once daily thereafter for 14 days. Body weights were obtained immediately prior to exposure on study day 0 and once daily thereafter for 14 days. A final body weight was collected for all animals that died on study. Animals in extremis or at the scheduled necropsy were euthanized by isoflurane anesthesia followed by exsanguination. The major organ systems of the cranial, thoracic and abdominal cavities were examined for all animals.
Statistics:
No data

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
ca. 3 151 ppm
Based on:
test mat.
95% CL:
>= 2 681 - <= 3 702
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
ca. 3 151 ppm
Based on:
test mat.
95% CL:
>= 2 681 - <= 3 702
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
ca. 3 151 ppm
Based on:
test mat.
95% CL:
>= 2 811 - <= 3 531
Exp. duration:
4 h
Mortality:
All animals in the 7443 ppm group died during the exposure. Four animals in the 3517 ppm group were found dead by study day 2. In addition, 4 animals in the 3517 ppm group were euthanized in extremis by study day 2. The justification for euthanasia of four animals in the 3517 ppm group was based on the severity and persistence of clinical signs. Total mortality was 0/10, 8/10 and 10/10 animals for the 1824, 3517 and 7443 ppm groups, respectively.
Clinical signs:
other: Clinical observations immediately following exposure included decreased respiration, shallow respiration, rales, labored respiration, lacrimation of the eyes, partial closure of the eyes and yellow material on the urogenital area for the 1824 and 3517 ppm
Body weight:
There were no remarkable changes in body weight. From study day 0 to 7, one female in the 1824 ppm group lost 1 gram. All animals surpassed their initial (study day 0) body weight by study day 14 and were considered normal.
Gross pathology:
Internal macroscopic findings noted for animals that died prior to the scheduled necropsy were dark red areas on the lungs, dark red discoloration of the lungs and clear fluid contents in the uterus for the 1824 and 3517 ppm groups; red discoloration of the corticomedullary junction in the kidneys, dark red discoloration of the liver, accessory spleen and cysts on the ovaries for the 3517 ppm group; and dark red discoloration of the adrenal glands, distended urinary bladder, opacity of the eyes and dark red areas on the urinary bladder for the 1824 ppm group. At the scheduled necropsy, macroscopic findings noted for animals in the 1824 ppm group were white areas on the spleen for 2 females, clear fluid contents in the uterus for 2 females and pale lungs for 1 male. There were no other macroscopic findings for animals at the scheduled necropsy.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated informationApprox 11.8mg/l (based on conversion mg/l=ppmxRMM/24000) where RMM is 90.2Criteria used for interpretation of results: EU
Conclusions:
In an acute inhalation study conducted to OECD 403 and to GLP (reliability score 1), the 4 hour LC50 of hydroxytrimethylsilane was 3151 ppm (11.8 mg/l) in rats. Significant clinical observations for the surviving animals during the 14-day post-exposure observation period consisted of yellow material on the urogenital area for the 1824 and 3517 ppm groups; decreased respiration, shallow respiration, rales, hypoactivity, prostration, ataxia, lacrimation of the eyes, partial closure of the eyes, decreased defecation, decreased urination, opacity of the eyes, brown material on the urogenital area and red material around the right eye, facial area and urogenital area for the 3517 ppm group; and yellow material on the dorsal rump and red material around the nose and on the dorsal trunk for the 1824 ppm group. All surviving animals in the 1824 and 3517 ppm groups were considered normal by study days 2 and 5, respectively.