Glycerol

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Reference

Endpoint:

short-term repeated dose toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

not stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results

Principles of method if other than guideline:

Two week aerosol study to set dose levels for a 13 week study. Study design appears to follow intent of OECD 412 but publication does not indicate that OECD 412 was followed.

GLP compliance:

not specified

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remarks on MMAD:

MMAD / GSD: MMAD <1.5 um (respirable)

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

6 hours/day

Frequency of treatment:

5 days/week

Remarks:

Doses / Concentrations:
1000, 2000 and 4000 mg/m3
Basis:
nominal conc.

No. of animals per sex per dose:

10/sex/dose level

Control animals:

yes

Dose descriptor:

LOAEC

Effect level:

1 000 mg/m³ air (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on local effects on the epithelium of the upper respiratory tract.

Critical effects observed:

not specified

ANALYSES:
- Actual dose level: 1000, 1930 and 3910 mg/m3 (98-100% of target)
- Homogeneity (uniformity): relative standard deviation 1.6-2.5% of mean value

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- Mortality: 2 males at 1000 mg/m3 and 1 male and 1 female at 2000 mg/m3
- Clinical signs: no treatment related effects
- Body weight gain: decreased in males and females at all concentrations (58-28% in females)
- Food consumption: no treatment related effects
- Clinical chemistry: glucose decreased in females at all concentrations (28-19%)
- Haematology: no treatment related effects
- Organ weights: no treatment related effects
- Gross pathology: no treatment related effects
- Histopathology: minimal to mild squamous metaplasia of the epiglottis in males and females at 0, 1000, 1930 and 3910 mg/m3 (1/10, 13/18, 16/19 and 13/14, respectively). Although a dose-related increase in the frequency of squamous metaplasia was not apparent, the frequency of mild metaplasia was greatest at the top dose (7 animals with minimal and 6 with mild).

STATISTICAL RESULTS: all effects mentioned showed statistical significance, except the decreased weight gain in males

Conclusions:

The LOAEL was 1000 mg/m3 based on local effects on the epithelium of the upper respiratory tract.

Executive summary:

The subacute toxicity of glycerol was examined following aerosol exposure. The LOAEL was 1000 mg/m3 based on local effects on the epithelium of the upper respiratory tract.

Data source

Reference

Reference Type:

publication

Title:

2-week and 13-week inhalation studies of aerosolized glycerol in rats

Author:

Renne R.

Year:

1992

Bibliographic source:

Inhal Toxicol 4:95-111

Materials and methods

Principles of method if other than guideline:

Two week aerosol study to set dose levels for a 13 week study. Study design appears to follow intent
of OECD 412 but publication does not indicate that OECD 412 was followed.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

propane-1,2,3-triol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Remark on MMAD/GSD:

MMAD / GSD: MMAD <1.5 um (respirable)

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

6 h

Concentrations:

1000, 2000 and 4000 mg/m3

No. of animals per sex per dose:

10

Control animals:

yes

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LC0

Effect level:

5 850 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: re-calculated from a 6 h exposure period

Effect levels 2

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5 850 mg/m³ air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortality in any of the doses during the initial 6 h of exposure (day 1).

Mortality during the 14-day exposure period: 2 males at 1000 mg/m3 and 1 male and 1 female at 2000 mg/m3 (time of death not reported), all animals in the high concentration group survived the 14-day exposure period.

Clinical signs:

other: no treatment related effects

Body weight:

Body weight gain: decreased in males and females at all concentrations (58-28% in females)

Gross pathology:

no treatment related effects

Any other information on results incl. tables

The 14 day inhalation study without mortality which used a high dose of 3900 mg/m3 for 6 hr/day 5 d/wk.   Using Haber’s rule that purports that toxicity is a function of total exposure suggests that a 6 hr exposure to 3900 mg/m3 a value of 23400 mgxhr/m3 is derived.  This can then be used to derive the concentration that would yield the same outcome if only 4 hr exposure, 5850 mg/m3. 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute inhalation toxicity of glycerin was examined in rats. An inhalation LC50 was not determined as there were no mortalities at the highest tested concentration ( 5.85 mg/L) which was above the limit concentration of 5 mg/L for aerosols as defined by the OECD guideline 403.