Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Comparable to a guideline study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
EU Method B.2 (Acute Toxicity (Inhalation))
GLP compliance:
yes (incl. certificate)
Test type:
other: The highest practical concentration that could be generated as a droplet-free vapour. The use of this concentration as a limit concentration for this study was recommended following consultation with the UK Health and Safety Executive.
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ethoxypropyl acetate
- Physical state: Liquid
- Analytical purity: 98.5%
- Storage condition of test material: Room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Rats were identified individually by a number tattooed on the tail.
- Source: Charles River UK Limited, Kent, England
- Age at study initiation: 6-8 weeks when received
- Weight at study initiation: 144 to 180 g when received
- Housing: Polypropylene cages with detachable wire mesh tops and floors. Cages were suspended on a movable rack. Animals remained in a holding room except during the exposure, and overnight following exposure when the animals were kept in a ventilated cabinet to allow for dispersal of any residual test substance.
- Diet: While in their cages, animals had free access to a measured excess amount of food (Labsure LAD)
- Water: While in their cages, animals had free access to tap water.

ENVIRONMENTAL CONDITIONS
- Temperature: The mean daily maximum and minimum temperatures of the holding room over the period of this study were 23 degrees C (S.D. = 1.3) and 20 degrees C (S.D. = 0.6).
- Humidity: The mean daily relative humidity of the holding room was 59% (S.D.= 7.1)

IN-LIFE DATES: From: To:
Exposures were conducted on 22 August, 1985.`

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The test substance was supplied to a glass generator at a constant flow rate of 0.21 ml per minute from a 100 ml syringe driven by a syringe pump.
- Exposure chamber volume: 0.13 cubic meters
- Method of holding animals in test chamber: The exposure chamber was divided by wire mesh partitions to provide 10 separate animal compartments.
- Source and rate of air: A supply of clean compressed dried air was connected to the generator and the supply pressure adjusted to give a flow rate of 25 liters per minute.
- Treatment of exhaust air: Each chamber was positioned inside a large cabinet equipped with an fan exhausting to atmosphere through a collection filter.
- Temperature, humidity, pressure in air chamber: Chamber temperature and relative humidity were recorded at the start of exposure and at 30 minute intervals during the exposure.
Mean chamber temperature was 24.2 degress C (S.D = 0.51) in the control chamber and 24.2 degrees C (S.D.= 0.35) in the test chamber.
Relative humidity was 34 (S.D.= 4.9) in the control chamber and 41 (S.D.= 1.6) in the test chamber.

TEST ATMOSPHERE
- Brief description of analytical method used: Air samples were taken from the chamber at 30 minutes, 1, 2, 3 and 4 hours during exposure, and analyzed by gas chromatography.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
> 4 h
Remarks on duration:
4 hours, followed by a 12 minute equilibration period (total exposure time was 4 hours, 12 minutes). 12 minutes was the calculated theoretical time required for the chamber concentration to reach 90% of its maximum value.
Concentrations:
The actual mean chamber concentration was 6.99 mg/l.
No. of animals per sex per dose:
5 males and 5 females.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed continuously during exposure for signs of reaction to the test substance and at least twice daily during the observation period. All rats were weighed daily from the day of receipt until the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: The lungs were removed, dissected clear of surrounding tissue and weighed in order to calculate the lung weight to body weight ratio. The lungs were infused with 10% buffered formalin. The lungs, liver and kidneys were preserved for possible microscopic examination.

Food and water intake was measured daily for each cage of rats, and the mean daily intake calculated.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 6.99 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: maximum achievable concentration
Mortality:
There were no deaths during the study.
Clinical signs:
Lacrimation, abnormal body posture and abnormal respiratory pattern were the main clinical signs evident during exposure. These signs were considered to be consistent with exposure to a mildly irritating vapour.

Approximately 18 minutes post exposure when the rats were removed for examination all animals were ataxic and had an abnormal respiratory pattern. All rats were normal in appearance and behaviour from Day 1 to Day 14.
Body weight:
There were slight reductions in bodyweight or reduced rate of gain for 1 day following exposure. Subsequently the rate of body weight gain for exposed rats was similar to that of the control animals.
Gross pathology:
There were no findings attributable to exposure.
Other findings:
- Organ weights: The lung weight to body weight ratio for all rats was considered to be within normal limits.
- Other observations: Food consumption was slightly reduced for 1-2 days and water consumption was reduced in female rats only for 2 days following exposure.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these results, the LCLo (4-hour) for ethoxypropyl acetate vapour is greater than 6.99 mg/l. This was the highest practical concentration that could be generated as a droplet-free vapour.
Executive summary:

In a guideline and GLP acute whole-body inhalation toxicity study in rats, a single 4-hour exposure to ethoxypropyl acetate at the highest practical concentration that could be generated as a droplet-free vapor, 6.99 mg/l, did not produce lethality. Lacrimation, abnormal body posture and abnormal respiratory pattern were the main clinical signs evident during exposure. These signs were considered to be consistent with exposure to a mildly irritating vapour.