Acetone

Epidemiological data

Administrative data

Endpoint:

epidemiological data

Type of information:

other: epidemiological study of workplace exposure

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study meets generally accepted scientific principles for an epidemiological study: well-characterized population exposed exclusively to acetone, adjustment for alcohol drinking and smoking habits, sufficient documentation of methods and of test result; restrictions of the study: no analysis of LOAELs possible for observed effects as no thresholds were specified and only time-weighted average concentrations are available; relationships between subjective symptom reporting and odour perception not investigated

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Relationship between acetone exposure concentration and health effects in acetat fiber plant workers

Author:

Satoh T, Omae K, Nakashima H, Takebayashi T, Matsumura H, Kawai T, Nakaza M, Sakurai H

Year:

1996

Bibliographic source:

Int Arch Occup Environ Health 68: 147-153

Reference 2

Reference Type:

other: collection of data for toxicological assessment

Title:

Toxicological review of acetone (CAS No. 67-64-1)

Author:

Environmental Protection Agency (EPA)

Year:

2003

Bibliographic source:

www.epa.gov/iris: EPA/635/R-03/004

Materials and methods

Study type:

cross sectional study

Endpoint addressed:

repeated dose toxicity: inhalation

Principles of method if other than guideline:

A cohort of acetone-exposed workers was compared with a cohort of non-exposed workers based on the following parameters: questionnaires on acute and chronic symptoms including eye irritation, neurobehavioral testing, hematological and serum biochemistry parameters

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

Method

Type of population:

occupational

Details on study design:

METHOD OF DATA COLLECTION
- Type: Questionnaire / Clinical tests / Neurobehavioral examinations

STUDY PERIOD:
autumn 1989

SETTING:
cross-sectional study

STUDY POPULATION
- Total population: 110 male acetate fiber factory workers
- Selection criteria: workers using acetone as a solvent in the production of cellulose-containing dope
- Total number of subjects participating in study: 110
- Sex/age/race: male, mean 37.6 (18.7-56.8) yrs, Japanese
- Length of employment: mean 18.9 (0.5-36.9) yrs
- Exposure length to acetone: 14.9 (0.5-34.3) yrs
- Smokers: 74.9 %
- Alcohol drinkers: 70.9 %
- Other: no protective device, no exposure to other solvents or toxic substances except to negligible amounts of machine oil

COMPARISON POPULATION
- Type: Reference group
- Details: 67 male nonexposed shift workers from same factory area not engaged in acetate manufacturing; possible background exposure to less than 5 ppm acetone
- Age: 41.9 (20.7-57.5) yrs
- Working period: 22.2 yrs (0.7-38.6) yrs
- Smokers: 70.5 %
- Alcohol drinking: 78.7 %

HEALTH EFFECTS STUDIED
- subjective symptoms (e.g. eye irritation, nausea, feeling in the head), neurotoxicity, haematological and serum biochemistry parameters

Exposure assessment:

measured

Details on exposure:

TYPE OF EXPOSURE: inhalation

TYPE OF EXPOSURE MEASUREMENT: Personal sampling / Biomonitoring blood / Biomonitoring urine
Environmental exposure levels: in the breathing zone using a liquid passive sampler
Alveolar air concentration: air samples collected at the start and the end of the workshift after two deep fresh air breaths, and holding of the third deep breath for 20 s.
Blood concentration: blood samples collected at the start of the shift on the 1st day and at the end of the shift on the 2nd day
Urine concentration: samples collected at the start and the end of the workshift
Acetone concentrations determined by gas chromatography.

EXPOSURE LEVELS:
Environmental exposure levels: time-weighted average level of acetone exposure assessed in the breathing zone using a liquid passive sampler

EXPOSURE PERIOD: study period two consecutive working days after 2 days without exposure.

POSTEXPOSURE PERIOD: no

DESCRIPTION / DELINEATION OF EXPOSURE GROUPS / CATEGORIES:
Environmental exposure levels: time-weighted average level of acetone exposure assessed in the breathing zone using a liquid passive sampler on two consecutive working days after 2 days without exposure.

Statistical methods:

Student's t-test or Welch's test used in univariate analysis to compare mean values for selected variables
Chi-square test or Fischer's exact test used for categorical data to compare the frequency of subjective symptoms
Analysis of covariance (ANCOVA) or Mantel-Haenszel method to adjust for the influence of age, alcohol drinking, and smoking status

Results and discussion

Results:

EXPOSURE
- Number of measurements: 110 per day
- Arithmetic mean: 351.9 ppm on 1st day, 360.5 ppm on 2nd day
- Range: 5-957 ppm on 1st day, 5-1212 ppm on 2nd day
- Exposure categories: low 0-250 ppm, middle 251-500 ppm, high >500 ppm

QUESTIONNAIRE ON SUBJECTIVE SYMPTOMS (For details see Table 1); clear dose-response relationships for the 3 exposure categories observed for most symptoms.
- during last 6 months: significant increases of heavy feeling in the head, nausea, faint feeling in the head, loss of weight, slow healing of an external wound;
- before starting daily work: significant increase of eye irritation, mild eye inflammation, reduction in working morale
- after finishing daily work: significant increase of eye irritation, tearing, acetone odor, nausea

Any other information on results incl. tables

Overview on acetone levels in environmental and alveolar air, in blood and urine:

- Environmental concentrations (N=288): 361.4 ppm or 860 mg/m3 (5-1212 ppm or 12-2880 mg/m3 )

- Alveolar air concentrations (N=293): 90.9 ppm (1-476)

- Blood concentrations (N=108): 66.8 mg/L (1-225)

- Urine concentrations (N=275): 37.2 mg (0.8-212)

Workers were classified to 3 exposure categories (low, middle, high) with the following cut-off values:

- Environmental concentrations: low exposure 0-250 ppm, middle exposure 251-500 ppm, high exposure >500 ppm

- Alveolar concentrations: low exposure 0-70 ppm, middle exposure 71-140 ppm, high exposure >141 ppm

- Blood concentrations: low exposure 0-45 mg/L, middle exposure 46-80 mg/L, high exposure >81 mg/L

- Urine concentration: low exposure 0-25 mg/L, middle exposure 26-50 mg/L, high exposure >51 mg/L

Table 1: Overview on symptoms significantly increased in acetone-exposed workers compared to unexposed control group

Symptoms		% Responders
Period of appearance	Description	Acetone-exposed N=110	Controls N=67
Within the last 6 months	Heavy feeling in the head	25.8*	9.8
	Nausea	24.7 *	8.0
	Faint feeling in the head	23.6 **	5.9
	Palpitations	31.5 * ^a	15.7
	Loss of weight	23.6 **	5.9
	Slow healing of an external wound	7.9 *	0.0
	Phlegm in the winter or at night	16.9 * ^a	5.9
Before starting daily work	Eye irritation	40.2 *	21.6
	Mild inflammation of eyes	22.5 **	5.9
	Reduction in working morale	32.4 *	13.7
During or after finishing work	Eye irritation	45.1 **	23.5
	Tearing	13.7 *	3.9
	Acetone odor	36.3 **	5.9
	Nausea	25.5 **	7.8

Significantly different from control group: * p<0.05, ** p<0.01

^a The significance of the prevalence of palpitations and phlegm in the winter or at night disappeared when the effects of alcohol drinking or smoking were adjusted by applying the Mantel-Haenszel method

Applicant's summary and conclusion

Conclusions:

Neurobehavioral examinations of workers exposed to a mean concentration of acetone of 361 ppm (range 5-1,212 ppm) revealed questionable effects without a clear dose response relationship. It is not possible to derive LOAELs from this study as no thresholds were given for significant effects and the time-weighted average does not reflect temporary high exposures.

Executive summary:

A cross-sectional study was carried out in 110 male acetone-exposed and 67 male nonexposed shift workers in an acetate fiber plant. The acetone workers ranged in age from 18.7 to 56.8 yrs (mean 37.6 yrs) and in length of acetone exposure from 0.5 to 34.3 yrs (mean 14.9 yrs). The nonexposed workers ranged in age from 20.7 to 57.5 yrs (mean 41.9 yrs). Acetone exposure levels in the breathing zone were 19.6 -1,018 ppm or 47 - 2420 mg/m³ (mean 364 ppm or 865 mg/m³) and were directly correlated with the acetone levels in alveolar air, urine and blood. There was no exposure to any other solvents or toxic substances. Neurobehavioral testing included finger tapping, simple reaction time, and choice reaction time to assess narcosis. Memory tests consisted of the Benton visual retention test and the digit span test. Questionnaires were performed for subjective symptoms in the 6 previous months, and before and after the daily work shift. Manifest Anxiety Scale scores and Self-rating Depression Scale scores were also assessed by questionnaire.

The prevalence of subjective symptoms with clear exposure-response relationship (no LOAEL specified) reported at the end of workshift was increased for eye irritation, tearing, and perception of acetone odor. For symptoms experienced during the previous 6 months prevalences were increased for heavy, vague or faint feeling in the head, nausea, loss of weight, and slow healing of external wounds. However, possible relationships between odour perception and reported subjective symptoms were not investigated. There were no effects on hematological and serum biochemistry parameters, phagocytic activity of peripheral neutrophils, or on the autonomous nervous system. Neurobehavioral examinations revealed questionable effects only in the subgroup of workers in the 30-44 yrs age range and only for the simple reaction time and the digit span test, but without a clear dose response relationship. It is not possible to derive LOAELs from this study as no thresholds were given for significant effects and the time-weighted average does not reflect temporary high exposures.