Acetone

Exposure related observations in humans: other data

Administrative data

Endpoint:

exposure-related observations in humans: other data

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Well-designed and well-documented study on relationships between perceived odour, irritation and reported health symptoms; focus on investigation of influence of odour and of occupational exposure by making use of suitable control groups and control substances; study acceptable as key study

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

Perceived odor, irritation and health symptoms following short-term exposure to acetone

Author:

Dalton P, Wysocki CJ, Brody MJ, Lawley HJ

Year:

1997

Bibliographic source:

Am J Ind Med 31: 558-569

Materials and methods

Type of study / information:

odour detection threshold, perceived irritation

Endpoint addressed:

respiratory irritation

Principles of method if other than guideline:

Groups of workers and control subjects exposed to 800 ppm acetone or 200 ppm phenylethyl alcohol (odorous control substance without irritating properties) for 20 min: pre- and post-exposure determination of odour detection threshold by two-alternative, forced-choice procedure (comparison blank vs. odorant); applying up-down-staircase method ; continuous rating of odour and irritation during the exposures; post-exposure questionnaire for irritation and health symptoms

Test material

Test material information

Constituent 1

Reference substance name:

Acetone

EC Number:

200-662-2

EC Name:

Acetone

Cas Number:

67-64-1

Molecular formula:

C3H6O

IUPAC Name:

propan-2-one

Details on test material:

purity: > 99.5% (high-performance liquid chromatography grade)

Method

Details on study design:

acetone-exposed workers (w): N=27, 4 m, 23 f, age 23-65 yrs, 14 smokers; subjects without acetone exposure (controls c): N=27, age- and gender-matched, 14 smokers; acetone exposure: median 12 yrs to 479 ppm, average exposure 585 ppm for N=18 subjects with a range of the average of 114-643 (all subjects
experimental exposure: 20 min to 800 ppm acetone: pre- and post-exposure odour detection threshold by two-alternative, forced-choice procedure (comparison blank vs. odorant); applying up-down-staircase method for assessing the threshold of detection; continuous rating of odour and irritation during the exposure; post-exposure questionnaire for irritation and health symptoms

Exposure assessment:

measured

Details on exposure:

Occupational exposure levels dependent on workplaces in ppm (average values for 1982-1994 / actual average values in 1995): N=18, 585 / 568 ppm; N=2, 387 / 416 ppm; N=2, 216 / 291 ppm; N=1, 643 / 648 ppm; N=1, 414 / 414 ppm, N=1 330 / 330; N=1, 216 / 350 ppm; N=1, 114 / 114 ppm

Results and discussion

Results:

Odour detection thresholds: pre-exposure median about 85 ppm in w and c; post-exposure median 89 and 278 ppm in w and c, shift in sensitivity w < c (not significant);
Perceived intensities of odour and irritation: odour rating: w weak to moderate, c strong to very strong; irritation rating: w weak, c moderate to strong; significant reduction by occupational exposure (p<0.001)
Time course of perceived intensities during 20 min exposure: odour rating: decrease w - 28%, c – 46%; irritation rating: w slight variation only, decrease c – 30%
Health symptoms: solvent-associated symptoms: for throat irritation, nasal irritation, lightheadedness, headache, nausea and drowsiness ratings of c > w (p<0.001); c: all rated as weak; w: weak nasal irritation, all other barely detectable); current irritation (perceived during the questionnaire): rated as weak by w and c, ratings of c > w (p<0.001)
somatic control symptoms: principally in the range of barely detectable; ratings of c > w for cough, stomachache, shortness of breath, heart palpitations (p<0.001)
Occupational acetone exposure: specific change in perceived intensities of irritation and odour of acetone, but no induction of general olfactory dysfunction; no correlations with individual exposure histories (exposure levels, cumulative exposure)
Odour most significant factor mediating the degree of perceived irritation for both w and c (r=0.92)
Response bias: ratings of irritation are not pure measures of irritation independent of odour; influence of bias to report irritation following exposure to an unknown chemical
Demographic factors: no influence of age, smoking habit on any variable

Any other information on results incl. tables

Rating of odour intensity during 20-min experimental exposure (significant findings):

Effect of compound:

Acetone exposure: workers: rating weak to moderate, control group: rating strong to very strong

Occupational exposure to acetone reduced perceived odour intensity of acetone relative to control subjects (p<0.001)

PEA exposure: comparable ratings in both groups: weak to moderate; odour of PEA rated as weaker as the odour of acetone (p<0.001)

Effect of exposure duration:

Decrease of odour intensity with increasing time of exposure both for acetone and PEA and for both groups (p=0.001)

Acetone: 20-min exposure produced 46% reduction in controls, 28% reduction in workers

PEA: 20-min exposure produced 30% reduction in controls, 36% reduction in workers

Rating of perceived irritation during 20-min experimental exposure (significant findings):

Effect of compound:

Acetone exposure: workers: rating weak, control group: rating moderate to strong

Occupational exposure to acetone reduced perceived irritation intensity of acetone relative to control subjects (p<0.001), effect showing correlation to odour perception

PEA exposure: similar ratings in both groups: workers barely detectable to weak, controls weak; irritation of PEA rated as weaker as the odour of PEA

Effect of exposure duration:

Decrease of irritation intensity with increasing time of exposure for acetone in controls only (p<0.001)

Odour detection thresholds:

Acetone:

Pre-exposure values (ppm) : no significant difference between workers and controls; median 86.10 and 83.90, mean±SEM 362.00±157.40 and 395.30±131.23, respectively

Post-exposure values (ppm): smaller shift in sensitivity in workers than in controls (not significant); median 89.20 and 278.30, mean±SEM 1960.00±1147.10 and 552.70±152.57, respectively

Symptom questionnaires: rating of symptoms

Solvent-associated symptoms (for details see Table):

Acetone exposure : workers: all symptoms in the range of “barely detectable” except for weak nasal irritation; controls: “barely detectable” eye irritation, headache and nausea; weak throat and nasal irritation, lightheadedness, and drowsiness
controls showed significantly higher ratings (p<0.001) than workers for the following items : throat irritation, nasal irritation, lightheadedness, headache, nausea and drowsiness

PEA exposure: all symptoms in the range of “barely detectable”; controls showed significantly higher ratings (p<0.001) than workers for the following items : lightheadedness, nausea

Comparison between acetone and PEA exposure: Controls showed significantly higher ratings for acetone compared to PEA (p<0.001) for the following items : throat irritation, nasal irritation, lightheadedness, headache. Treating irritant responses to PEA as an irritant baseline: for workers frequency and ratings of solvent-associated symptoms were similar for acetone and PEA; for controls higher ratings for throat and nasal irritation and lightheadedness for acetone compared to PEA exposure

Somatic control symptoms:

Acetone exposure : all symptoms in the range of “barely detectable” except for weak bad taste in controls; controls showed significantly higher ratings (p<0.001) than workers for the following items : cough, stomachache, shortness of breath, heart palpitations

PEA exposure: all symptoms in the range of “barely detectable”; no significant differences between controls and workers

Comparison between acetone and PEA exposure: Controls showed significantly higher ratings (p<0.001) for acetone compared to PEA (p<0.001) for the following items : bad taste, itching

Comparison between groups:controls rated significantly more health symptoms than workers.

Current irritation:both groups rated as weak with significantly higher rating by controls (p<0.001)

Table: Compilation of intensity ratings in symptom questionnaires for exposure to 800 ppm acetone for 20 min

Symptom category	Item	Workers		Controls
		Mean	SD	Mean	SD
Solvent-associated symptoms	Throat irritation	2.43	0.48	8.59 *	0.65
	Eye irritation	3.77	0.64	4.63	0.61
	Nasal irritation	6.74	0.61	14.43 *	0.51
	Lightheadedness	2.07	0.51	12.57 *	0.62
	Headache	2.14	0.52	5.09 *	0.56
	Nausea	1.34	0.38	5.17 *	0.64
	Drowsiness	2.30	0.47	5.64 *	0.69
Current irritation		2.54	0.54	5.17 *	0.63

* significant difference between control and workers

Category boundaries of LMS:³1.37 barely detectable, 5.46 – 15.74 weak

Relationships between perceived odour intensity, irritation intensity and response bias:

Correlation odour vs. irritation: most significant factor mediating the degree of perceived irritation from acetone for both workers and controls appeared to be the perceived intensity of odour (r=0.92)

Exposure history: Occupational exposure to acetone appeared to produce a very specific change in the perceived intensities of irritation and odour but apparently did not impair the perception of odour or irritation more generally (comparison acetone vs. PEA), lack of induction of general olfactory dysfunction. No correlations found in the group of workers for individual exposure histories (exposure levels, cumulative exposure)

Response bias: responses to the non-irritant control PEA suggested that the ratings of irritation are not pure measures of irritation independent of odour; influence of bias to report irritation following exposure to an unknown chemical

Demographic factors: no influence of age, smoking habit on any variable

Applicant's summary and conclusion

Conclusions:

Subjective ratings of irritation are strongly influenced by odour and bias to report irritation. The perceived irritation elicited by exposure to 800 ppm acetone varies with the individual's history of exposure to acetone with a significant effect for long-term occupational exposure, and a smaller effect during a 20-minute short-term exposure.

Executive summary:

Perceived odour, irritation and health symptoms were compared in two age- and gender matched groups of acetone-exposed workers and controls without previous acetone exposure (N=27, 4 m, 23 f, age 23-65 yrs, 14 smokers). Workers had an exposure history with a median duration of 12 yrs to an average concentration of 479 ppm acetone (range of average 114-643 ppm). Test persons were individually exposed for 20 min in an exposure chamber either to the irritant acetone (800 ppm = 1900 mg/m³) or to the non-irritant odorous control substance phenylethyl alcohol (PEA 200 ppm) with the irritant responses to PEA being treated as an irritant baseline. During these exposures intensities of perceived odour and irritation were rated every minute applying a computerized line scale, the validated Labeled Magnitude Scale (LMS). Immediately before and after exposure odour detection thresholds applying a two-alternative, forced-choice, modified staircase method were measured both for acetone and butanol used as control substance as exposure to acetone should not effect sensitivity to butanol. Further, the frequency of occurrence and the perceived intensity of 7 regional irritation symptoms, typical for solvent exposure, of 14 somatic or control symptoms, and of the current perceived irritation were assessed both for acetone and PEA by a computerized questionnaire immediately after each exposure employing the LMS.

Occupational exposure to acetone significantly reduced perceived odour and irritation intensities of acetone relative to previously unexposed control subjects. Ratings of odour were weak to moderate, and strong to very strong, those of irritation were weak and moderate to strong, in workers and controls, respectively, with perceived irritation showing a correlation to odour perception. Similar ratings were found in both groups for PEA. Perceived odour intensity significantly decreased during the course of the 20-min exposure for both groups and both for acetone (46% reduction in controls, 28% reduction in workers) and PEA (30% reduction in controls, 36% reduction in workers). In contrast, irritation intensity showed a significant decrease in controls only. Pre-exposure values of odour detection thresholds showed no significant difference between workers and controls (median about 85 ppm), whereas post-exposure values were similar in workers (median 89 ppm) and showed a greater shift in sensitivity in workers (no significant difference for median of 278 ppm).

Generally, controls rated significantly more health symptoms than workers. Concerning solvent-associated symptoms, controls showed significantly higher ratings (p<0.001) than workers for the following items, throat irritation, nasal irritation, lightheadedness, headache, nausea and drowsiness (controls: all rated as weak; workers: nasal irritation rated as weak, all other rated as barely detectable). For the PEA exposure, all ratings were in the range of barely detectable with controls showed significantly higher ratings only for lightheadedness and nausea. For workers frequency and ratings of solvent-associated symptoms were similar for acetone and PEA, for controls ratings for throat and nasal irritation, and lightheadedness were higher for acetone. Current irritation, perceived during the questionnaire, was rated as weak by both with significantly higher rating by controls. Somatic control symptoms principally were in the range of barely detectable. Following acetone exposure, control persons showed significantly higher ratings than workers for some items (cough, stomachache, shortness of breath, heart palpitations). PEA exposure resulted in no significant differences between controls and workers.

In conclusion, odour was the most significant factor mediating the degree of perceived irritation from acetone for both workers and controls. Occupational exposure to acetone appeared to produce a very specific change in the perceived intensities of irritation and odour but apparently did not impair the perception of odour or irritation more generally (comparison acetone vs. PEA) indicating a lack of general olfactory dysfunction. In the group of workers no correlations were found for individual exposure histories (exposure levels, cumulative exposure). Responses to the non-irritant control substance PEA suggested that the ratings of irritation are not pure measures of irritation independent of odour. Further, an influence of bias to report irritation following exposure to an unknown chemical was indicated. Otherwise, demographic factors, as age, gender or smoking habit were without effect on any variable.