Registration Dossier

Administrative data

Description of key information

LC50 (oral) > 5000mg/kg
LDL0 (inhalation, 4hrs) > 6.99mg/l
LC50 (dermal) ~ 20,000mg/kg (prediction based on surrogate substance)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1985
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD 401)
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Each animal was identified by cage number and ear punching.
- Source: Interfauna UK Ltd., Huntingdon, Cambridgeshire, England
- Age at study initiation: Approximately 4 to 6 weeks
- Weight at study initiation: 100 to 127 g prior to dosing (Day 1) in the main study.
- Fasting period before study: Access to food only was prevented overnight prior to and approximately 4 hours after dosing.
- Housing: Animals were housed in groups by sex in metal cages with wire mesh floors.
- Diet: Ad libitum access to a standard laboratory rodent diet (Labsure LAD 1), except during the fasting period
- Water: Ad libitum access to tap water
- Acclimation period: A minimum of 5 days prior to start of the main study.

ENVIRONMENTAL CONDITIONS
- Temperature: The mean daily minimum and maximum temperature of the animal room were 21 degrees C and 23 degrees C.
- Humidity: The mean daily relative humidy value of the animal room was 63%.
- Air changes: Approximately 15 changes per hour.
- Photoperiod: 12 hours of artificial light in each 24 hour period.

IN-LIFE DATES: From: 20 August, 1985 To: 3 September, 1985
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
The test substance was administered as supplied at a constant volume of 5.3 ml/kg (specific gravity = 0.94).
CLASS METHOD (if applicable)
- Limit dose
Doses:
5 g/kg bodyweight
No. of animals per sex per dose:
Preliminary study – 2 males and 2 females
Main study – 5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: Preliminary study – 5 days
Main study – 14 days
- Frequency of observations and weighing: Animals were observed soon after dosing; then at frequent intervals for the remainder of Day 1. On subsequent days the animals were observed at least twice per day. Individual body weights were recorded on Days 1 (day of dosing), 8 and 15 of the main study.
- Necropsy of survivors performed: yes
- Other examinations performed: Clinical signs were recorded at each observation interval.
Sex:
male/female
Dose descriptor:
LDLo
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities.
Clinical signs:
Signs of reaction to treatment observed shortly after dosing in all rats were piloerection, hunched posture, abnormal gait (waddling), lethargy, pallor of the extremities and increased salivation.
Body weight:
All animals in the main study gained weight during the study period.
Gross pathology:
Terminal necropsy findings were normal.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute lethal oral dose to rats of ethoxypropyl acetate was greater than 5.0 g/kg bodyweight.
Executive summary:

In a GLP and guideline acute oral toxicity study in rats, a single dose of ethoxypropyl acetate administered by gavage at the limit dose of 5.0 g/kg did not produce lethality.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Adequate. LD50 not observed at maximum tested dose

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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.
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
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.`
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.
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Adequate. LC50 not observed at maximum tested dose

Acute toxicity: via dermal route

Endpoint conclusion
Quality of whole database:
No data on test substance

Additional information

The acute toxicity of ethoxypropyl acetate is very low. The rat oral LDLo value is greater than 5,000 mg/kg, and the rat inhalation LCLo value is greater than 6,990 mg/m3 (4-hour, whole body, vapour), which was the highest practical concentration of droplet-free vapour that could be generated. Data available on a surrogate substance suggests that the dermal LD50 will be in excess of 20,000mg/kg..

Justification for classification or non-classification

Available data indicates that the toxicity by the oral and inhalation routes is low and well above the thresholds for classification. Toxicity by the dermal route can also be predicted to be similarly very low. Inhalation of vapour up to the maximum vapour concentration caused some adverse effects in animals (abnormal body posture and abnormal respiratory pattern). These signs were considered to be consistent with exposure to a mildly irritating vapour and not necessarily CNS effects. There does not appear to be any evidence to support classification for acute CNS effects (R67 or STOT(SE).