Acetone

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

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 with the following restrictions: single test concentration, daily exposure time limited to 3 hrs, limited number of endpoints investigated, less detailed documentation; study acceptable for weight of evidence approach

Data source

Reference

Reference Type:

publication

Title:

Evaluation of toluene and acetone inhalant abuse. II. Model development and toxicology

Author:

Bruckner JV, Peterson RG

Year:

1981

Bibliographic source:

Toxicol Appl Pharmacol 61: 302-312

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Examined endpoints: body weight gain, organ weights (liver, kidney, brain, lung), histopathology of liver, kidney, brain, lung, and heart, serum clinical chemistry

GLP compliance:

not specified

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:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ARS/Sprague-Dawley, Madison, Wisconsin
- Age at study initiation: 4 w
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5-7 d

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: 16 liter-chamber
- Method of holding animals in test chamber: cages used for housing were also used for exposure, with a wire mesh bottom placed into the cages instead of the feed and wood shaving bedding material
- Air flow rate: 24 L/min

TEST ATMOSPHERE
- Brief description of analytical method used: gas chromatographic analysis at 30-sec intervals
- Samples taken from breathing zone: no data

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

gas chromatographic analysis at 30-sec intervals

Duration of treatment / exposure:

2, 4, 8 w

Frequency of treatment:

5 d/w, 3 hrs/d

Doses / concentrations

Remarks:

Doses / Concentrations:
19,000 ppm corresponding to 45,000 mg/m3
Basis:
nominal conc.

No. of animals per sex per dose:

9 per timepoint: N=5 for serum biochemical and organ weight investigations, N=4 for histopathological examination

Control animals:

yes, sham-exposed

Details on study design:

Post-exposure observation group: 8 w exposure followed by 2 without exposure

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: twice per week

FOOD CONSUMPTION: No data

WATER CONSUMPTION: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at 4, 8 w of exposure and after 2 w post-observation period
- Animals fasted: No data
- How many animals: 5
- Parameters examined: serum glutamic-oxaloacetic transaminase (SGOT), lactate dehydrogenase (LDH), blood urea nitrogen (BUN)

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

ORGAN WEIGHTS: liver, kidney, lung, brain at 0, 4, 8 w of exposure and after 8 w of exposure and 2 w of recovery

HISTOPATHOLOGY: liver, kidney, lung, heart, brain at 0, 4, 8 w of exposure and after 8 w of exposure and 2 w of recovery

Statistics:

Student's t-test

Results and discussion

Effect levels

Dose descriptor:

NOAEC

Effect level:

19 000 ppm

Sex:

male

Basis for effect level:

other: overall effects

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

The only significant changes were decreases of absolute weights of kidney (only after 4 w of exposure) and of brain weight (at 4 and 8 w of exposure) in comparison to control animals. These changes were reversible within 2 w of post-observation. Weight gain also showed a tendency to depression (never significant). There were no recognizable histopathological changes in these tissues.

Table 1: Changes of absolute organ weights (g wet weight; N= 5 rats/timepoint)

Organ	Group	Timepoint
		0	4 w exposure	8 w exposure	2 w post-exposure
Brain	Control	1.49	1.71	1.91	1.84
	Exposed		1.60 *	1.70 *	1.80
Kidney	Control	0.71	1.65	2.26	2.22
	Exposed		1.38 **	2.12	2.29

* statistically significant, p<0.02

** statistically significant, p<0.01

Applicant's summary and conclusion

Conclusions:

After 8 weeks of exposure of rats to 19,000 ppm (3 hrs/day) there were no indications of an adverse systemic toxic effect from the investigated endpoints.

Executive summary:

Groups of male rats (N=9) were exposed to a single concentration of 19,000 ppm acetone (45,000 mg/m³) for 2,4 or 8 weeks, 5 days/week and 3 hours/daily. Under the conditions of this exposure there were no indications of an adverse toxic effect from the investigated endpoints being body weight gain, organ weights (liver, kidney, brain, lung; N=5), histopathology of liver, kidney, brain, lung, and heart (N=4) and serum clinical chemistry parameters (SGOT, LDH and BUN; N=5). Slight significant decreases of weights of brain (at 4 and 8 w of exposure) and of kidney (only at 4 w of exposure) correlated with a depression of body weight gain (not significant) and were without a histological correlate. Based on the investigated endpoints the NOAEC is 19,000 ppm acetone or 45,000 mg/m³.