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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:
key study
Study period:
1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This guideline compliant sub-chronic exposure study is used to derive an acute inalation LC50 value
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1996

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: EPA OTS 798.2450 (90-Day Inhalation Toxicity)
Principles of method if other than guideline:
This study assesses the 90-day sub-chronic inhalation toxicity of butyl acetate. In the absence of mortality in this study, the highest exposure concentration of 3000 ppm can be used as a conservative estimate of the LC50.
GLP compliance:
yes
Test type:
other: subchronic exposure
Limit test:
no

Test material

Constituent 1
Reference substance name:
N-butyl acetate
EC Number:
204-658-1
EC Name:
N-butyl acetate
Cas Number:
123-86-4
IUPAC Name:
butyl acetate
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): n-butyl acetate
- Physical state: clear liquid
- Analytical purity: >/= 99.9%
- Laboratory Project ID: 940305I7
- Purity test date: 1994-09-09
- Lot/batch No.: 4014967 and 4010784

Read across from n-butyl acetate to n-hexyl acetate is considered acceptable based on structural similarity and similar toxicity profiles

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Kingston (Stone ridge, NY)
- Age at study initiation: 60 days
- Weight at study initiation: 271 +/- 7 g (males); 215 +/- 8 g (females)
- Fasting period before study: no
- Housing: individually during non expsure periods
- Diet: Certified Rodent Diet (Agway Prolab RMH 3200, ground chow), ad libitum except during exposure
- Water: ad libitum, except during exposure
- Acclimation period: 12 days


ENVIRONMENTAL CONDITIONS
- Temperature: 67-75°F
- Humidity: 46-60%
- Photoperiod (hrs dark / hrs light): 12/12

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: 4200 L stainless-steel and glass inhalation chambers
- Method of holding animals in test chamber: cages
- System of generating vapour: test substance was metered into glass distillation columns packed with glass beads; filtered, compressed air was passed through the glass bead-packed columns to evaporate the test substance; distillation columns were heated to about 50°C to enhance vaporization; the resultant vapour was directed via glass tubing to a tee just upstream of the inhalation chamber where it was mixed with filtered, conditioned outside air
- Temperature, humidity in air chamber: 21.1-24.7°C; 36.7-68.7%
- Air flow rate: 836 to 965 Lpm
- Air change rate: 12 to 14 air changes per hour
- Method of particle size determination: Micro Laser Particle counter (µLPC-301, Particle Measuring Systems, Inc, Coulder, USA); indicating that an aerosol of the test subsance was not present
Analytical verification of test atmosphere concentrations:
yes
Remarks:
MIRAN IA infrared gas analyzer set at wavelength of 3.38 µM. Chamber vapour samples were continuously collected from each chamber through TEFLON tubing. Valve position was periodically changed to sample from each chamber at least once each hour.
Duration of exposure:
6 h
Remarks on duration:
5 days per week for 13 weeks
Concentrations:
500, 1500 and 3000 ppm; calculated to be equivalent to 2.6, 7.7, 15.3 mg/L
No. of animals per sex per dose:
15
Control animals:
yes
Details on study design:
- Dose selection rationale: Range finding study: 2-Weeks repeated exposure in which animals were exposed to 0, 750, 1500 or 3000 ppm n-butyl acetate. The test substance produced concentration-related reductions in general activity levels during exposure periods. Animals appeared to acclimate to the 750 and 1500 ppm concentrations but not to 3000 ppm. Mean body weights for the female 1500 ppm animals and for the 3000 ppm male and female animals were lower than the control group on Days 7 and 14, but no statistically significant differences were noted. 3000 ppm was selected as an exposure concentration that would produce overt signs of toxicity, and 500 ppm was selected as an exposure concentration that was expected to have no effect. An exposure concentration of 1500 ppm was selected as the intermediate exposure concentration.
Statistics:
Bartlett's test, one-way analysis of variance, Duncan's multiple range test, Kruskal-Wallis H-test and Mann-Whitney U-test. Not applicable to acute assessment of data

Results and discussion

Preliminary study:
Not applicable
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 3 000 ppm
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: No deaths occurred at any exposure concentration in this study.
Sex:
male/female
Dose descriptor:
LC50
Effect level:
>= 15.3 mg/L air
Based on:
test mat.
Exp. duration:
6 h
Remarks on result:
other: No deaths occurred at any exposure concentration in this study.
Mortality:
No mortality follwoing a singkle exposure
Clinical signs:
other: At concentrations of 1500 or 3000 ppm (or 750 ppm in preliminary study) transient reduced activity levels , occasional cases of sialorrhea and tearing noted following one exposure but lasting for only few days.
Body weight:
No data available for weights after a single exposure, in the main study bodyweights and food consumption were recorded at weekly intervals.
Gross pathology:
Not done until completion of two-week or 13-week exposure period

Any other information on results incl. tables

Effects (acute, transient signs of reduced activity levels, decreased body weight and feed consumption, signs of upper respiratory tract irritation in the nasal passages) were only observed in the high- (3000 ppm) and mid-concentration (1500 ppm) group; there was no systemic, organ-specific toxicity.

The mean time weighted analytical exposure concentration for the 500 ppm (2.4 mg/L) group was 548 ppm (2.6 mg/L))

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
repeated exposure to n-butyl acetate for 6 hours per day for five days a week for 13 weeks at dose concentrations of 500, 1500 or 3000 ppm resulted in acute, transient signs of reduced activity levels during exposure to 1500 and 3000 ppm. Decreased body weight and feed consumption were noted for the 1500 and 3000 ppm groups, but there was no systemic or organ-specific toxicity. Signs of upper respiratory tract irritation were seen in the nasal passages of 1500 and 3000 ppm animals, but there was no evidence of pulmonary toxicity.

The effects following the first single exposure were similar to effects observed in the subsequent days, no specific effects of acute exposure were identifiable from this data set
Executive summary:
This study used 6 -hour daily inhalation exposures of 500, 1500 and 3000 ppm of the read-across substance n-butyl acetate. In the absence of mortality in any exposure group, the highest concentration can be used as a conservative estimate of the acute inhalation LC50 value. Male and female Sprague-Dawley rats (15 animals/sex/dose group) were exposed to nominal concentrations of 0, 500, 1500 or 3000 ppm of n-butyl acetate for 6 hours per day, 5 days per week for 13 consecutive weeks. The time-weighted average analytical concentrations were within 10% of the target concentrations. No deaths occurred.

Repeated exposure to n-butyl acetate for 6 hours per day for five days a week for 13 weeks at concentrations of 500, 1500 or 3000 ppm resulted in acute, transient signs of reduced activity levels during exposure to 1500 and 3000 ppm. Decreased body weight and feed consumption were noted for the 1500 and 3000 ppm groups, but there was no systemic or organ-specific toxicity. Signs of upper respiratory tract irritation were seen in the nasal passages of 1500 and 3000 ppm animals, but there was no evidence of pulmonary toxicity.

The effects following the first single exposure were similar to effects observed in the subsequent days, no specific effects of acute exposure were identifiable from this data set.

The acute LC50 is therefore estimated to be >3000ppm (15.3 mg/L).

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