Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1979-05-09 to 1979-06-14
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1979
Report Date:
1979

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
additive
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Central Institute for the Breeding of Laboratory Animals TNO, Zeist, The Netherlands
- Weight at study initiation: males: 180 g, females: 135 g
- Fasting period before study: none
- Housing: 5 animals per cage, stainless steel cages
- Diet: ad libitum the Institute's stock diet for rats
- Water: ad libitum unfluoridated water

ENVIRONMENTAL CONDITIONS
- Temperature: 21 +/- 1 °C
- Humidity (%): 50-60


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: stainless steel exposure chamber
- Exposure chamber volume: 1.5 m3
- Source and rate of air: total airflow of 1.6 m3/h
- System of generating particulates/aerosols: nebulizer provided with a baffle to remove large rdroplets from the mist produced
- Method of particle size determination: particle size determinations and counts were carried out in samples taken from the atmosphere in the chamber with a Cascade Impactor

TEST ATMOSPHERE
- Brief description of analytical method used: analysis of the test atmosphere was performed gravimetrically, samples were takne by passing a measured quantity of the test atmosphere through a Cambridge glassfibre filter at intervals of about 1.5 h
- Samples taken from breathing zone: yes
- Particle size distribution: maximum diameter 6.7 µm, 80 % of the mist consisted of droplets with a diameter of 1.7-3.3 µm


Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
2.56, 1.77, 1.55, 1.38, 1.30 g/m3 (measured)
No. of animals per sex per dose:
5
Control animals:
no

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 500 mg/m³ air
Based on:
test mat.
95% CL:
1 400 - 1 610
Exp. duration:
4 h
Mortality:
All animals of the highest dose group died until day 4 as well as 2 males and all females of the 1.77 g/m3 dose group, 3 males and 4 females of the 1.55 g/m3 dose group, 2 males and 2 females of the 1.38 g/m3 dose group and 2 males of the lowest (1.3 g/m3) dose group.
Clinical signs:
other: Restlessness during the first half an hour was observed. During exposure, animals kept their eyes closed and some had wet noses. After exposure mouth breathing was observed in the higher doses.
Body weight:
Animals lost weight during the first week of observation period. Surviving animals gained weight during the second week.
Gross pathology:
no data

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the LC 50 value of 1.5 g/m3 (1.5 mg/L) the test substance has to be classified for acute toxicity after inhalation into category 4.
Executive summary:

The acute inhalation toxicity of the test substance (60 % in Di-isobutyl phthalate) was tested on 50 male and 50 female Wistar rats. The animals were individually exposed to the aerosol at concentrations of 2.56, 1.77, 1.55, 1.38 and 1.30 g/m3 (5 males anf 5 females per doese group) for 4 hours. The animals were observed for a period of 14 days afterwards. All animals of the highest dose group died until day 4 as well as 2 males and all females of the 1.77 g/m3 dose group, 3 males and 4 females of the 1.55 g/m3 dose group, 2 males and 2 females of the 1.38 g/m3 dose group and 2 males of the lowest (1.3 g/m3) dose group. Restlessness during the first half an hour of exposure was observed. During exposure, animals kept their eyes closed and some had wet noses. After exposure mouth breathing was observed in the higher doses. A weight loss was observed during the first week of the observation period, but the surviving animals gained weight again in the second week. An LC 50 value of 1.5 mg/L was detemined.