Registration Dossier

Toxicological information

Acute Toxicity: inhalation

Currently viewing:

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
05.10.1998 to 22.06.2000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to a national standard method, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2000
Report Date:
2000

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
EPA OPPTS 870.1300 (Acute inhalation toxicity)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
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): Dow Corning Z-6020 Silane
- Substance type: Alkoxysilane
- Physical state: Liquid
- Stability under test conditions: No data
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited
- Age at study initiation: 7-8 wk
- Weight at study initiation: 186-345g
- Fasting period before study: no
- Housing: Stainless steel sheet and wire mesh suspended cages (holding cages)
- Diet (e.g. ad libitum): Ad libitum (except during exposure)
- Water (e.g. ad libitum): Ad libitum (except during exposure)
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21± 2
- Humidity (%): 55± 10
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 09.11.1998 To: 06.04.1999

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: whole body exposure chamber
- Exposure chamber volume: The whole body exposure chambers were 51 cm x 51 cm x 38 cm. The chambers were fitted with a pyramidal top section with an enclosed volume of approximately 120 litres.
- Method of holding animals in test chamber: Individual compartments
- Source and rate of air: Compressed air line at flow rate of 25 l/min
- Method of conditioning air: filtered, dried and oil-free
- System of generating aerosols: The test substance was metered at a constant rate from a polypropylene syringe mounted on a syringe pump to a stainless steel concentric jet atomiser. The aerosol produced passed through a 2-piece glass elutriator prior to entering the exposure chamber. During the first exposure with animals the test substance was observed to form a solid substance on contact with water. It was considered that the water vapour produced by the animals during exposure resulted in most of the silane in the chamber being converted to an aerosol of this solid.
- Method of particle size determination: Two additional air samples were taken during the exposure, at a sampling rate of 2 l/min, using a Marple cascade impactor. The amount of test substance collected on the stages of the sampler was determined gravimetrically. The particle size distribution of the test substance was assessed using linear regression analysis of the probit of the cumulative percentage of the total particles collected, smaller that the cut-point of each stage, against the logarithm of the cut-point of each stage.
- Treatment of exhaust air: Test atmosphere was extracted through a perforated base into a large extract cabinet exhausting to atmosphere through an absolute filter.
- Temperature, humidity, pressure in air chamber: 21-23 oC, 39-61%, pressure not clear

TEST ATMOSPHERE
- Brief description of analytical method used: At least five samples of air were removed from the test chamber at intervals during each exposure in order to determine the concentration of the test aerosol. Following the first exposure each air sample was withdrawn through a pre-weighed glass fibre filter mounted in an open face filter holder. The filters were re-weighed following sampling for gravimetric analysis of the test aerosol. For the first test group exposure only, in addition to sample collected on glass fibre filters, attempts were made to collect samples using sintered glass bubblers containing toluene as trapping agent to determine the actual silane concentration by chemical analysis. It had previously been determined that the aerosol of the silane formed a solid substance on contact with water vapour in air, which could not be analysed chemically with the method established. Therefore analysis of the test atmosphere produced from the test substance was analysed by gravimetric means only.
- Samples taken from breathing zone: Not clear from information given.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
Target: 0.5, 1.0, 1.5, 2.0 and 5.0 mg/L
Analysed: 0.515, 1.06, 1.49, 2.44 and 5.75 mg/L
No. of animals per sex per dose:
Five
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed continuously for signs of reaction during exposure and at least twice daily throughout the observation period. The clinical signs were recorded at the end of the chamber equilibrium period, 0.25, 0.5 and 1.0 hours into exposure then at hourly intervals during the remainder of the exposure. Signs were also recorded immediately after exposure and at 1 and 2 hours after exposure. During the observation period, signs were recorded twice daily. All rats were weighed at least twice during the week prior to exposure, immediately before exposure and weekly during the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: The amount of food consumed by each cage of rats was measured from weigh day to weigh day throughout the study. The amount of water consumed by each cage of rats was measured daily from Day 2 of the observation period following the gross observation of reduced consumption in the test rats. A complete macroscopic examination of each rat was performed. The lungs, liver and kidneys were weighed.
Statistics:
None

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.49 - < 2.44 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
See Table 2.
Clinical signs:
other: During exposure: Signs related to exposure to the test aerosol comprised exaggerated breathing and partially clossed eyes in all test groups and reduced motor activity in exposure groups 0.515 to 2.44 mg/L. During the observation period: Irregular noisy
Body weight:
A dose-related reduction in body weight gain over the observation period was observed in animals from 0.515 to 1.49 mg/L.
Gross pathology:
Severely congested lungs were observed in all deceased animals. The observation is considered to be associated with the cause of death. Areas of severe congestion together with pale raised hardened areas were also observed in the surviving female exposed to 5.75 mg/L. Pale raised lungs were also observed in the lungs of a proportion of surviving rats of both sexes in all other groups exposed to the test aerosol.
Other findings:
Food consumption by test groups was lower than that of the control group during the observation period.

Surviving female rats exposed to 2.44 or 5.75 mg/L had lung weights greater than control rats. In all other surviving animals from other test groups there were no differences in organ weights that were considered to be a direct effect of exposure to the test aerosol. Lower liver weights observed in test group survivors were considered to be a secondary effect of reduced body weight gains.

Any other information on results incl. tables

Table 2 Summary of mortality data

 Group (mg/l)  Mortality      
   Male  Female  Total
 0  0/5  0/5  0/10
 0.515 0/5   0/5  0/10
 1.06  0/5  0/5  0/10
 1.49  0/5  0/5  0/10
 2.44  5/5  3/5  8/10
 5.75  5/5  4/5  9/10

Applicant's summary and conclusion

Interpretation of results:
other: CLP/EU GHS criteria are met, Category 4 classification is required according to Regulations (EC) No 1272/2008.
Conclusions:
In an acute inhalation (aerosol) study conducted to EPA OPPTS 870.1300, which is comparable to OECD 403, and to GLP (reliability score 1) the LC50 for N-(3-(trimethoxysilyl)propyl)ethylenediamine was 1.49 -2.44 mg/L.