Acetone

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

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; publication in Japanese language, evaluation based on information in English language available from summary and figures in the original publication and from secondary literature; as a consequence information on test conditions is limited; study acceptable for weight of evidence approach

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

On the cutaneous absorption of acetone (In Japanese)

Author:

Fukabori S, Nakaaki K, Tada O

Year:

1979

Bibliographic source:

J Sci Labour 55: 525-532

Reference 2

Reference Type:

other: Collection of data for toxicological assessment

Title:

Toxicological profile for acetone

Author:

ATSDR (Agency for Toxic Substances and Disease Registry)

Year:

1994

Bibliographic source:

Agency for Toxic Substances and Disease Registry, U.S. Department of Health and Human Services, Public Health Service, May 1994, p. 1-276

Reference 3

Reference Type:

other: Collection of data for toxicological assessment

Title:

Environmental Health Criteria for Acetone

Author:

WHO

Year:

1998

Bibliographic source:

Environmental Health Criteria 207: 1-159

Materials and methods

Principles of method if other than guideline:

Dermal absorption of acetone was studied in human volunteers after exposure by acetone-soaked cotton swabs, monitoring of acetone concentration in blood, alveolar air and urine

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

Test animals

Species:

human

Administration / exposure

Type of coverage:

open

Duration of exposure:

(A) 2 hrs/day for 4 consecutive days: exposures were from 10 a.m. to 12. a.m.
(B) 4 hrs/day for 4 consecutive days: exposures were from 10 a.m. to 2 p.m.

Doses:

not specified

No. of animals per group:

Not specified

Details on study design:

APPLICATION OF DOSE: via cotton swabs soaked in acetone

TEST SITE
- Preparation of test site: no data
- Area of exposure: 12.5 cm2
- % coverage: no data
- Type of cover / wrap if used: none

SITE PROTECTION: no

REMOVAL OF TEST SUBSTANCE
- Removal of application device: cotton swabs were removed
- Washing procedures and type of cleansing agent: no
- Time after start of exposure: 2 or 4 hrs

SAMPLE COLLECTION ((no further details available from information in English language)
- Collection of blood: daily before start of exposure and after termination of exposure
- Collection of urine: daily before start of exposure, after 1 and 3 hrs of exposure, and at 2, 4, 8, and 15 hrs post-exposure, and 2, 8, 15, 21, 23, 26, and 36 hrs after the last exposure
- Collection of alveolar air: daily before start of exposure, every hour during exposure and 10 hrs post-exposure (every hour from 10 a.m. to 0 a.m.), and at 20, 23, 26, 31, and 41 hrs following the last application

Results and discussion

Absorption in different matrices:

- Blood: rapid absorption with peak levels at termination of each application
- Urine: peak levels within 1 and 2 hr after termination of the daily 2- or 4-hr exposure

Percutaneous absorption

Remarks on result:

other:

Any other information on results incl. tables

From the alveolar air and urine concentrations, it was estimated that a 2 -hr dermal exposure was equivalent to 2-hr inhalation exposure to 120 -355 mg/m³(50 -150 ppm), and a 4 -hr dermal exposure was equivalent to a 2 -hr inhalation exposure to 590 -1,190 mg/m³(250 -500 ppm).

Table 1: Blood levels (µg/mL) resulting from dermal application of acetone (estimated from graphic representation)

Application	1st day		2nd day		3rd day		4th day
Sampling time point	before	after^a	before	after ^a	before	after ^a	before	after ^a
2 hr exposure	1	4	1	5	1	12	1	9
4 hr exposure	1	26	1	31	1	29	1	44

 ^a sampling timepoint not specified

Table 2: Alveolar air levels (ppm) during and after dermal application of acetone (estimated from graphic representation)

Application

1st

2nd

3rd

4 th

Sampling timepoint

b.a.

term

4 p.a.

7 p.a.

10 p.a.

b.a.

term

10 p.a.

b.a.

term

10 p.a.

b.a.

term

10 p.a.

20 p.a.

38 p.a.

2 hr exposure

< 1

5

2.5

2

1

< 1

5

< 1

< 1

12

2

< 1

10

1

< 1

< 1

4hr exposure

< 1

27

16

10

5

< 1

30

5

< 1

25

3

< 1

34

5

< 1

< 1

b.a.: before application; term.: at termination of application; p.a.: hrs post application

Table 3: Urine concentrations (µg/mL) during and after dermal application of acetone(estimated from graphic representation)

A: 2 hr exposure

Application

1st

2nd

3rd

4 th

Sampling timepoint

b.a.

1 e

1 p.a.

3 p.a.

13 p.a.

1 e

1 p.a.

3 p.a.

13 p.a.

1 e

1 p.a.

3 p.a.

6 p.a.

13 p.a.

1 e

1 p.a.

3 p.a.

6 p.a.

13 p.a.

25 p.a.

Urine conc.

< 2

3

8

5

< 1

3

11

6

< 1

5

11

8

10

4

6

13

9

12

2

< 1

B: 4 hr exposure

Application

1st

2nd

3rd

4th

Sampling timepoint

b.a.

1 e

3 e

2 p.a.

4 p.a.

8 p.a.

15 p.a.

3 e

2 p.a.

15 p.a.

3 e

2 p.a.

15 p.a.

3 e

2 p.a.

15 p.a.

21p.a.

urine conc.

< 1

6

22

38

37

9

6

22

29

4

23

40

2

22

29

5

< 1

Sampling timepoints: b.a.: before application; e: hrs of duration of exposure; p.a.: hrs post application

Applicant's summary and conclusion

Conclusions:

In human volunteers acetone is rapidly absorbed during dermal application with peak blood levels occurring at the termination of each application.
Excretion occurs via expired air and via urine.

Executive summary:

Dermal absorption was investigated in human volunteers after exposure of a 12.5 cm² area of skin to acetone by uncovered application of cotton swabs soaked in acetone (dose not specified: rough estimation of doses of about 6 and 20 mg/kg bw/d for 2 and 4 hrs of exposure). Repeated exposure was for 2 hrs or 4 hrs daily for 4 consecutive days, and acetone concentrations in blood, alveolar air and urine were measured. From the available information in English language no details are available on test conditions. The authors noted that it was not possible to completely prevent a low exposure by inhalation (0.95 -1.4 mg/m³corresponding to 0.4 -0.6 ppm in the breathing zone).

Acetone was rapidly absorbed during dermal application as indicated by peak blood and alveolar air levels occurring at the termination of exposure, and peak urine levels occurring within 1 and 2 hr after termination of the daily 2- or 4-hr exposure, respectively. Generally, levels in blood, alveolar air and urine were more than doubled when extending the duration of exposure from 2 hrs to 4 hrs. Levels in blood returned to background before start of the next exposure. Alveolar air and urine levels reached background level before the next 2-hr exposure started. For the 4 hr-exposure, alveolar air and urine levels were still slighty elevated when the next treatment started. However, about 20 hrs after the last exposure, exhalation and urinary excretion were principally at the background level.