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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: This study was conducted according to the appropriate OECD test guideline and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
only 2 concentrations tested
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: CDF®(F-344)/ CrlBR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not reported.
- Age at study initiation: 66 d (group 1) and 57 d (group 2)
- Weight at study initiation: 179-207 g (males) and 129-135 g (females)
- Housing: Individual stainless steel wire mesh cages.
- Diet: Certified pelleted rodent chow® #5002 provided ad libitum except during exposure.
- Water: Tap water was supplied ad libitum except during exposure.
- Acclimation period: Group 1 animals were acclimated for a period of 16 days. Group 2 animals were acclimated for a period of seven days.

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

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: Stainless steel and glass exposure chamber.
- Exposure chamber volume: 160 Liters.
- Source and rate of air: Compressed air at 20 L/min.
- System of generating particulates/aerosols: The test article was metered via a syringe drive (Harvard Model 22) to a glass vaporisation column (2.5 cm² diameter x 22 cm² height) filled approximately three-quarters full with glass beads ranging from 4-6 mm in diameter. The test article was delivered to the centre of the glass beads where compressed air entering the base of the column at 20 L/min, measured by a flow meter (Fischer & Porter, FP-1-27-G-10/55), facilitated vaporisation. The test material was swept through a condensation trap and into the exposure chamber. Additional dilution air measured by a flow meter (Fischer & Porter, FP-4-21-G-10/55) was used to decrease the vapour concentration to the desired level.
- Method of particle size determination: gravimetrically.
- Treatment of exhaust air: The test atmosphere was exhausted to a fume hood.
- Temperature, humidity in air chamber: 24 °C and 2% - Group 1. 23 °C and 6% - Group 2. The low relative humidity resulted from the dry compressed air used to generate the vapour.

TEST ATMOSPHERE
- Brief description of analytical method used: Exposure atmosphere was measured using Infrared spectrophotometer (IR) analysis methods (Wilks Miran 1A Model 5688).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: The exposure atmosphere was judged to have no aerosols present. Negligible amounts were collected during the sampling for the particle size determination.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.):Not reported
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Infrared spectrophotometer (IR) analysis methods (Wilks Miran 1A Model 5688).
Duration of exposure:
4 h
Concentrations:
0.5 (Group 1) and 1.3 mg/L (Group 2).
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Observed for pharmacotoxic signs pre-exposure and immediately after exposure; two times daily during the 14-day post-exposure period, one for pharmacotoxic signs and once for mortality only. Body weights were recorded just prior to the exposure, and at 7 and 14 days post-exposure and when animals were found dead.
- Necropsy of survivors performed: yes. All animals were euthanized by intraperitoneal sodium pentobarbital overdose and exsanguinations via the abdominal aorta and underwent complete necropsy.
- Other examinations performed: clinical signs, body weight, organ weights, histopathology.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 500 - < 1 300 mg/m³ air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
500 mg/m³ – One female died on Day 13 post administration
1300 mg/m³ – All the animals died by Day 13 post administration
Clinical signs:
500 mg/m³ –During the two weeks post-exposure period the significant pharmacokinetic signs observed for these animals were death, gasping, wheezing, laboured breathing, slow respiration, decreased activity and excessive lacrimation.
1300 mg/m³ – During the two weeks post-exposure period the significant signs observed were death, decreased activity, laboured breathing, wheezing, corneal opacity, gasping and excess lacrimation.
Body weight:
500 mg/m³ – All animals lost weight during the first post-exposure observation week (approximately 13% for males and 11% for females) based on mean group body weight. During the 2nd week males started regaining weight but females continued to lose.
1300 mg/m³ - All animals lost weight during the first week (approximately 19% for males and 11% for females) and none survived to the 2nd week.
Gross pathology:
500 mg/m³ – One male and three females were observed with red discoloration of the lung ranging from trace to moderate.
1300 mg/m³ – All animals exhibited red discoloration of the lungs from mild to severe. No other significant macroscopic abnormalities were observed.

Any other information on results incl. tables

Table 3. Number of Animals Found Dead on Day of Study:

Dose (mg/L)

Study Day

0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

0.5

0

0

0

0

0

0

0

0

0

0

0

0

0

1

0

1.3

0

0

2

1

0

0

1

0

0

1

1

2

1

1

NA

NA- Not Applicable, all animals dead.

Applicant's summary and conclusion

Interpretation of results:
toxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Acute inhalation toxicity study conducted according to OECD 403 and GLP, identified a LC50 in the range of >0.5 < 1.3 mg/L for triethoxysilane.