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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:
weight of evidence
Study period:
29 Feb 1998 - 11 Mar 1998
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
GLP - Guideline study, tested with the source substance bis(2-ethylhexyl)l adipate (CAS 103-23-3). In accordance 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
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
(1981)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Version / remarks:
(1992)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Version / remarks:
(1984)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OTS 798.1150 (Acute inhalation toxicity)
Version / remarks:
(1992)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): [trade name]
- Substance No.: 97/492-1
- Date of production: 07 Nov 1997
- Physical state: colourless, clear liquid
- Analytical purity: 99.7% (according to analytical report 97L00845)
- Lot/batch No.: # 22513
- Stability: The stability of the test substance over the study period has been proven by reanalysis (analytical report 98L00166)
- Homogeneity: homogeneous (analytical report 97L00845 )
- Storage condition of test material: at room temperature

Test animals

Species:
rat
Strain:
other: SPF Wistar/Chbb:THOM
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, Germany
- Age at study initiation: approximately 8-9 weeks
- Weight at study initiation: 284±9.5 g
- Housing: individually in cages type DK III (Becker, Germany) without bedding
- Diet: KLIBA rat/mouse/hamster laboratory diet 10 mm pellets (Klingentalmühle AG, Kaiseraugst, Switzerland), ad libitum during the post-exposure observation period
- Water: ad libitum during the post-exposure observation period
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose/head only
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction)
- Exposure chamber volume: approximately 55 L
- Method of holding animals in test chamber: the animals were restrained in tubes and their snouts projected into the inhalation chamber
- Source and rate of air: compressed air; supply air flow : 1500L/h, exhaust air flow: 1350 L/h
- Method of conditioning air: not specified (temperature and humidity were measured in 30 min-intervals). No surveillance of the oxygen content in the inhalation system was performed. The air change was judged to be sufficient to prevent oxygen depletion by the breathing of the animals and the concentration of the test substance used could not have a substantial influence on oxygen partial pressure .
- System of generating aerosol: Amounts of the test substance were supplied to the two-component atomizer by means of the piston metering pump. By means of compressed air, the aerosol was produced inside the aerosol mixing vessel and was passed through the cyclonic separator into the exposure system. Flow rate of the test substance preparation to the atomizer was 35.0 mL/h .
- Method of particle size determination: The following equipment was used for the particle size determination: Stack Sampler Mark III (Andersen), Vacuum Compressed Air Pump (Millipore), Sampling probe (internal diameter 6.9 mm), Limiting orifice 3 L/min, Balance: Sartorius M3P and Sartorius LC 1201S. Before sampling, the impactor was assembled with preweighed glass-fiber collecting discs, and a backup particle filter. The impactor was connected to the vacuum pump and one sample was taken from the breathing zone of the animals not earlier than 30 minutes after the beginning of the exposure. The sample volume was 9 L. After sampling the impactor was taken apart and the collecting discs and the backup particle filter were re-weighed. The amounts of material adsorbed to the walls of the impactor and in the sampling probe (wall losses) were also determined quantitatively.
- Temperature, humidity, pressure in air chamber: 21.5 °C, 2.1% rel. humidity

TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric determination of the inhalation atmosphere concentration.
- Samples taken from breathing zone: yes (immediately adjacent to the animals' noses)

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: please refer to table 1
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.4 µm/3.0
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
5.7 mg/L
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: A check for overt clinical signs of toxicity or mortality as well as a check for the presence of feed and drinking water was made twice a day on workdays and once daily on weekends and public holidays. Detailed clinical observations were recorded for each animal separately several times during exposure and at least once on each workday in the observation period.
- Frequency of weighing: prior to exposure, after 7 days and after 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
A Probit analysis was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.7 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality occurred throughout the study period.
Clinical signs:
other: Clinical examination revealed irregular and accelerated respiration as well as attempts to escape and piloerection. No clinical signs could be detected from post dosing day 5 onward.
Body weight:
All animals of this study gained body weight as expected.
Gross pathology:
No gross pathological abnormalities were detected in the animals at study termination.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified