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Description of key information

Data are available for the acute toxicity of hexyl acetate following oral, dermal and inhalation exposure.  Low toxicity is demonstrated for all exposure routes.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
41 500 mg/kg bw
Quality of whole database:
A screening study provides limited methodological data but is sufficient for the purposes of hazard characterisation and classification.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
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
Reason / purpose for cross-reference:
reference to same study
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
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
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
Preliminary study:
Not applicable
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

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))

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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
15 300 mg/m³
Quality of whole database:
A guideline-compliant 90-day inhalation toxicity study is supported by an acute inhalation study with the submission substance. Data are consistent in idicating a very low potential for acute inhalation exposure.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Data reported January 25, 1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Limited methodological detail but sufficient for the purposes of hazard classification
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
no
Remarks:
conducted prior to adoption of GLP principles
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
No additional information available
Type of coverage:
not specified
Vehicle:
not specified
Details on dermal exposure:
No information provided
Duration of exposure:
No information provided
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
Ten rabbits used in total but no breakdown by sex available
Control animals:
no
Details on study design:
Ten rabbits were exposed by dermal application to 5000 mg/kg bw of hexyl acetate. The rabbits were observed for 14 days following dosing. Mortality and clinical signs were recorded.
Statistics:
Not required
Sex:
not specified
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: One death on the day of treatment
Mortality:
One rabbit died on day 1.
Clinical signs:
Prior to death the single decedent animal exhibited signs of sluggishness
Body weight:
No data
Gross pathology:
No data
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal toxicity of hexyl acetate in the rabbit was found to be >5000 mg/kg bw under the conditions of this study.
Executive summary:

Following dermal exposure to 5000 mg hexyl acetate/kg bw, one of ten rabbits exposed died on Day 1 of the observation period. The decedent developed signs of sluggishness prior to death. The acute dermal toxicity of hexyl acetate in the rabbit was therefore found to be >5000 mg/kg bw under the conditions of this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Two studies are available and report acute dermal LD50 values of >5000 and >20000 mg/kg bw.

Additional information

The acute oral LD50 of hexyl acetate in the rat is shown to be 41.5 mL/kg bw (~41.5 g/kg bw). Two studies of acute dermal toxicity in the rabbit report LD50 values of >5000 mg/kg bw and >20 mL/kg bw (~20 g/kg bw). Data indicate the acute inhalation LC50 to be >15.3 mg/L.

Justification for selection of acute toxicity – oral endpoint

Only one study available for this endpoint

Justification for selection of acute toxicity – inhalation endpoint

No deaths were observed in a 90-day inhalation toxicity study performed using the read-across substance n-butyl acetate, which used 6-hour daily exposures of up to 3000 ppm (15.3 mg/L; 15300 mg/m3).  This study is supported by the results of a screening study performed using an 8-hour exposure to hexyl acetate at the saturated vapour concentration (calculated to be 1426 ppm, 9.04 mg/L or 9040 mg/m3).  The data are therefore consistent in demonstrating a very low potential for acute inhalation toxicity.

Justification for selection of acute toxicity – dermal endpoint

This study reports a lower LD50 value

Justification for classification or non-classification

The results of acute oral, dermal and inhalation toxicity studies show very low toxicity and do not trigger the classification of hexyl acetate for acute toxicity according to the CLP Regulation.

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