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Administrative data

Endpoint:
direct observations: clinical cases, poisoning incidents and other
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
year of publication: 1993
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented publication which meets basic scientific principles

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Study type:
study with volunteers
Endpoint addressed:
eye irritation
respiratory irritation
Principles of method if other than guideline:
measurement of irritation to the mucous membranes of the eyes and the airways
GLP compliance:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
N-butyl acetate
EC Number:
204-658-1
EC Name:
N-butyl acetate
Cas Number:
123-86-4
Molecular formula:
C6H12O2
IUPAC Name:
butyl acetate
Details on test material:
- Name of test material (as cited in study report): n-butyl acetate

Method

Type of population:
other: healthy subjects without occupational experience of solvent exposures
Subjects:
- Number of subjects exposed: 24
- Age: 24 - 47 years
- Sex: male and female
Ethical approval:
confirmed, but no further information available
Route of exposure:
inhalation
Reason of exposure:
intentional
Exposure assessment:
measured
Details on exposure:
Exposures were carried out in an air conditioned open system exposure chamber (volume 12 m3, 11 air changes per hour, at 22-23°C). The solvent was injected in the influent air stream by a high-performance liquid chromatography pump (Gilson 302). The concentration of n-butyl acetate was monitored at atmospheric pressure by an infrared spectrophotometer (Miran 80 Foxboro) equipped with a 45°C thermostated 20 m gas cell at 8.39 Fun, with 3.68 as the reference wavelength. The air samples were taken from the upper central section of the chamber.
Examinations:
see below

Results and discussion

Any other information on results incl. tables

Category Scales Measuring Irritation

In experiment I, changes in categorical ratings of irritation from baseline level before exposure were not significant for any of the items rated. In experiment II, category rating scales of irritation, differed significantly (p-values < 0.01 and 0.001) between the control and the exposure conditions for all items except irritation to the skin. In experiment III, significant differences in categorical ratings were found for the items concerning irritation to the throat (p < 0.01), breathing difficulties (p < 0.05), and sensation of a bad smell (p < 0.001).

Category Scales Measuring CNS Symptoms

There were no significant effects in any of the three experiments an the CNS symptoms, either from exposure levels, or from time in exposure.

Eye Redness

After 20 min of exposure, at each level, one person had increased redness in one eye. After 4h in the control condition, an enhancement in eye redness was found in two persons, and after exposure to 700 mg/m3, it was found in six persons. No subject was found to have decreased eye redness following any exposure. There were no significant differences between the proportions of subjects with augmented eye redness following the different exposure conditions, or between 20 min and 4 h in the control condition.

Lipid Layer Thickness

The eye lid positions at the occurrence of the interference phenomenon were significantly (about 1/4) lower after 4 h exposure to the control condition and 700mg/m3 during baseline conditions. The difference between 700 mg/m3 and the control condition could not be tested (see Table II, Fig. 3). Wilcoxon's rank sum test showed a significant negative difference (about 1/4) between 4 h and 20 min in the control condition (sum of ranks = 105/171, critical sum = 99/165 at p = 0.05).

Break-Up Time

No significant effects an the tear film break-up time were found in any of the experiments.

Conjunctival Epithelial Damage

No significant differences in the proportion of subjects with red-stained cells were found following the different exposure conditions.

Blinking Frequency

Blinking frequency during the control condition was unchanged from the baseline level of 12 blinks/min. Blinking frequency during the 1,400 mg/m3 exposure session rose from the baseline level of 9/min to 12/min. The increase from baseline level to last recording (minute 15) was statistically significant (p = 0.02).

Pulmonary Functions

In the shorter time exposure of experiment II, there were only minor changes. Thus, FEVImeasured during exposurewas unchanged, and FVC was slightly lower (-1.4%, p < 0.05) following 20 minexposure to 1,400 mg/m3of butyl acetate as compared to control conditions. FEVIand PEF were not significantly different when comparing high exposure and thecontrol condition, but were slightly lower following butyl acetate than pre-exposurevalues (FEVI—1.7%, p = 0.05, and PEF —3.0%, p = 0.01). Following 4 h exposure,MEF25was slightly higher (5%, p < 0.01) than after 4 h in the control condition. FEVImeasured during exposures was not affected.

Applicant's summary and conclusion

Conclusions:
Under the conditions used to test irritation to mucuous membranes of the airways and the eyes, the test substance showed no relevant irritation potential.
Executive summary:

Iregren et al. (1993) tested the irritating potential of n-butyl acetate in nonsmoking volunteers in a series of three different chamber studies. The irritative effects were evaluated on the basis of the subjective feeling of irritation, clinical examination of eye irritation and the lung function. The first group of volunteers (Experiment I) was exposed to concentrations of 350, 700, 1050 and 1400 mg/m³ (72.5, 145, 220 and 290 ppm). Exposure lasted 20 minutes and was repeated four times in intervals of 24 h. Under these conditions, subjects reported irritation to the throat, difficulties in breathing and a sensation of a bad smell. There were trends towards increasing effects with increasing exposure level, although the observed effects were only weak and no significant differences in effect size between any of the exposure concentrations and the baseline level before exposure were observed.

In the second test (Experiment II), volunteers were exposed to 70 (“control” level) and 1400 mg/m³ n-butyl acetate (14.5 and 290 ppm) two times for 20 min at intervals of 7 h. In this test, ratings for irritation of all sites except skin, differed significantly between 290 ppm and the control, although the irritation was not felt to be severe. Accustoming to the bad smell occurred depending on exposure time and exposure level.

In the third part of the study, subjects were exposed to 70 and 700 mg/m³ n-butyl acetate (14.5 and 145 ppm) twice for 4 h within seven days. Significant differences in the extent of throat irritation, difficulties in breathing and sensation of a bad smell were reported, but no differences in ocular irritation were determined. Altogether, the authors of the study concluded a rather low irritating potential of n-butyl acetate.

The study is reliable with restrictions (RL2).