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Exposure related observations in humans: other data

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Endpoint:
exposure-related observations in humans: other data
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
year of publication: 2005
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:
2005

Materials and methods

Type of study / information:
Data on sensory irritation (eye blinks)
Endpoint addressed:
eye irritation
Principles of method if other than guideline:
4h inhalational exposure of test subjects with either constant or variable concentrations of the test substance. Blinking rates was assessed by electromygraphic eye blink recordings.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-ethylhexanol

Method

Ethical approval:
confirmed and informed consent free of coercion received
Details on study design:
Male subjects (with and without self-reported multiple chemical sensitivity, MCS) were exposed by inhalation for 4 h to 1.5, 10 and 20 ppm 2-EH. The conditions during exposure were either constant or varying concentrations, i.e. minimum and maximum values ranged between 1.39 - 1.58 ppm (average 1.5 ppm), 1.23 - 20.20 ppm (average 10 ppm) and 1.76 - 42.07 ppm (average 20 ppm). At higher concentrations severe eye irritation occurred therefore they were not tested. The change from minimum to maximum concentration took about 30 min and vice versa, therefore the duration for a whole cycle is 1 h.
Exposure assessment:
measured
Details on exposure:
TYPE OF EXPOSURE:
a) constant concentration
b) variable (peak) concentration

OTHER CONDITIONS:
- exposure in chambers
- relative humidity: 40%
- temperature: 23 °C
- air exchange rate: 10 times/h

TYPE OF EXPOSURE MEASUREMENT: Area air sampling of exposure unit every 2.5 minutes by automatic gas chromatographic measurement

EXPOSURE LEVELS (as vaporized solvent):
a) 1.5, 10 or 20 ppm
b) 1.39 - 1.58 ppm (average 1.5 ppm), 1.23 - 20.20 ppm (average 10 ppm) and 1.76 - 42.07 ppm (average 20 ppm)

EXPOSURE PERIOD: 4 h
All subjects were tested under three conditions of either condition a or b. Exposure took place on three days with 2 or 3 days placed between without exposure (exposure free interval).

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES:
-in general healthy young males
1) with self-reported multiple chemical sensitivity (sMCS) (conditions a) n=12; b) n=8)
2) or age matched control (conditions a) n=12; b) n=12)

Results and discussion

Results:
Exposure under constant conditions revealed a statistically significant increase in blinking frequency of the eye lid only at the highest concentration used 20 ppm in comparison to 1.5 ppm. With variable exposure concentrations averaging at 10 and 20 ppm (including peaks of about 20 and 40 ppm) there was a significant difference in comparison to 1.5 ppm with both concentrations. Acceleration of blinking frequency was 2- respectively 3-fold. During the study peak exposure concentrations yielded the highest irritation scores.

Any other information on results incl. tables

a) eye blink rates for constant conditions:

- 1.5 ppm: 14/min

- 10 ppm: 17/min

- 20 ppm: 21/min; statistically significant increase in comparison to 1.5 and 10 ppm exposure

- sMCS group shows higher starting values than control group (statistically significant)

b) eye blink rates for variable conditions:

- 1.5 ppm: 12/min

- 10 ppm: up to 24/min at peak exposure; statistically significant increase (2fold) in comparison to 1.5 ppm exposure; at minimum exposure about 12/min

- 20 ppm: up to 30/min at peak exposure; statistically significant increase (~3fold) in comparison to 1.5 ppm exposure; at minimum exposure about 12/min

- no statistically significant difference between control group and subjects with sMCS

Applicant's summary and conclusion

Conclusions:
After inhalational exposure to vapour an indication for potential sensory eye irritation, based on measurement of blinking frequency, at concentrations of about 20 ppm was found for the test item (i.e. NOAEC = 10 ppm).
Executive summary:

In this reliable study (RL2) sensory irritation data were assessed measuring eye blinking frequency. Exposure of young males (n = 12 healthy subjects and 8 with sMCS; single exposure; 4 h) to three concentrations of 2 -ethylhexan-1 -ol under constant conditions (1.5, 10, 20 ppm) revealed a statistically significant increase in blinking frequency only at the highest concentration used (frequency of about 14/min at 1.5 ppm, 17/min at 10 ppm, 21/min at 20 ppm).

With variable exposure concentrations averaging at 10 and 20 ppm (including peaks of about 20 and 40 ppm; n = 12 healthy subjects and 12 with sMCS) there was a significant difference in comparison to 1.5 ppm with both concentrations. Acceleration of blinking frequency was 2- respectively 3-fold. During the study peak exposure concentrations yielded the highest irritation scores.

There was no difference between the two groups of subjects with and without MCS, except some differences at the start of exposure . Eye blink frequency is a suitable and sensitive indicator of sensory irritation. Thus if exposures which are inducing significant differences for this parameter are avoided no further consequences of sensory irritation have to be suspected (Kiesswetter et al., 2005).