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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study.
Cross-reference
Reason / purpose:
reference to same study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: Multi-Substance Rule for the Testing of Neurotoxicity 40 CFR Part 799 (58 FR 40262)
Deviations:
no
Principles of method if other than guideline:
Method: other: Acute neurotoxicity test
Method as dictated in the Multi-Substance Rule for the Testing of Neurotoxicity 40 CFR Part 799 (58 FR 40262).
GLP compliance:
yes
Test type:
other: acute toxicity testing as part of a neurotoxicity test
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Analytical purity: Purity of ethyl acetate was greater than 99%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc, Portage, MI
- Age at study initiation: Approximately 35 days old upon receipt
- Housing: The animals were individually housed for the duration of the study in stainless steel, wire mesh cages (22.5 x l5.Sx 18.0 em), except during exposures and the motor activity evaluations. DACB~ (Deotized Animal Cage Board, Shepherd Specialty Papers, Inc.) was placed under each stainless steel cage and changed regularly. Cages were changed and sanitized at least once every 2 weeks.
- Diet (e.g. ad libitum): Ground Lab Diet™ The Richmond Standard™ Certified Rodent Diet #5002 (PMI Feeds, Inc.) was available ad libitum except during exposures and neurobehavioural analyses
- Water (e.g. ad libitum): Available ad libitum except during exposures
- Acclimation period: Approximately 3-4 weeks


ENVIRONMENTAL CONDITIONS
- Temperature: routinely maintained at 66 - 77 deg F
- Humidity: routinely maintained at 40 - 70%
- Photoperiod (hrs dark / hrs light): 12-hours (approximately 0500 to 1700 for light phase)

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Inhalation Chamber Description and Operation - The chambers, constructed from stainless steel with glass windows for animal observation, were rectangular (101 x 101 x 60.2 cm) in shape with a pyramidal top and bottom. The volume of each chamber was approximately 900 1, and the airflow was approximately 200 l/min (13 air changes/hour). A Dwyer Magnehelic® pressure gauge (Dwyer Instruments, Inc., Michigan City, IN) was used to monitor chamber airflow., The theoreticallyderived time (t99) required for each chamber to reach 99% of the target concentration was calculated to be approximately 21 minutes.

Chamber temperature and relative humidity were recorded approximately 2 times during each hour of exposure.

Vapor Generation - Liquid ethyl acetate was metered into a heated glass evaporator.

The oxygen content of the exposure chambers was measured during preliminary level setting and during the 6-hour exposure on June 28, 1994.

Chamber concentrations of ethyl acetate vapor were analyzed approximately twice each hour during each 6-hour exposure by flame ionization gas chromatography.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
by gas chromatography
Duration of exposure:
6 h
Concentrations:
0, 600, 3000, 6000ppm (0, 2.25, 11.25, 22.5 mg/l respectively)
No. of animals per sex per dose:
14 animals per sex per dose group.
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 15 days
Statistics:
The data for quantitative, continuous variables were intercompared for the 3 exposure groups and the control group by use of Levene’s test for equality of variances, analysis of variance (ANOVA), and t-tests. The t-tests were used when the F value from the ANOVA was significant. When Levene's test indicated similar variances, and the ANOVA was significant, a pooled t-test was used for pairwise comparisons. When Levene's test indicated heterogeneous variances, all groups were compared by an ANOVA for unequal variances followed, when necessary, by a separate variance t-test for pairwise comparisons.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LCLo
Effect level:
> 6 000 ppm
Exp. duration:
6 h
Mortality:
No mortality occurred.
Clinical signs:
other: There were no exposure related clinical signs noted during the exposure, although an external stimulus was not presented. There were no clinical signs related to exposure noted on the morning following exposure or on study day 7 and 14.
Body weight:
Loss of body weight was noted in animals from all three exposure groups on the day following exposure. No other effects on body weight or body weight gain were noted.

Any other information on results incl. tables

Decreases in MA were observed for males and female rats exposed to 300 or 6000 ppm ethyl acetate when measured approximately 1 hour post-exposure.  The decrease in motor activity persisted for the 6000 ppm exposure groups when measured on the morning of the day following exposure.  There were no other changes in MA noted for any groups during the post-exposure assessment period.  FOB endpoints indicative of sedation were observed solely at the initial post-exposure measurement period in animals exposed to 3000 or 6000 ppm.  The NOEL for systemic toxicity was less than 600 ppm based upon the transient decrease in body weights noted on the first day after exposure.  The NOEL for neurotoxicity was 600 ppm. The LOEL for neurotoxicity (sedation) was 3000 ppm. 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information based on mortality results Criteria used for interpretation of results: EU
Executive summary:

In a guideline and GLP study inhalation study, carried out using a 6 -hr whole body exposure, the LCLo was established to be >6,000 ppm (22.5 mg/L), the maximum dose tested. The acute NOEC for neurotoxicity was 600 ppm (2.25 mg/L) based on sedation at higher concentrations.

Synopsis

LC0>6000ppm (22.5mg/l)