Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
data from handbook or collection of data
Remarks:
from competent authority reviewd data

Data source

Referenceopen allclose all

Reference Type:
review article or handbook
Title:
Unnamed
Year:
2013
Reference Type:
publication
Title:
Unnamed
Year:
2018

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 412 (28-Day (Subacute) Inhalation Toxicity Study
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Mass median aerodynamic diameter (MMAD):
>= 1.1 - <= 1.2 µm
Analytical verification of doses or concentrations:
yes
Duration of treatment / exposure:
28 d
Frequency of treatment:
6 hours a day, on 5 days a week
Doses / concentrationsopen allclose all
Dose / conc.:
10 mg/m³ air (nominal)
Dose / conc.:
50 mg/m³ air (nominal)
Dose / conc.:
150 mg/m³ air (nominal)
No. of animals per sex per dose:
5

Results and discussion

Effect levels

open allclose all
Dose descriptor:
NOAEC
Remarks:
systemic toxicity
Effect level:
150 mg/m³ air
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: histopathological effects were seen in any other organ outside the respiratory tract
Dose descriptor:
NOAEC
Remarks:
local effects
Effect level:
10 mg/m³ air
Based on:
act. ingr.
Sex:
male/female
Basis for effect level:
other: local portal of entry effects (irritation of respiratory tract)

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The inhalation exposure of rats to MEA for 28 days caused concentration-related lesions in larynx, trachea and lung. No histopathological effects were seen in any other organ outside the respiratory tract. The NOAEC for systemic toxicity is the highest concentration tested of 150 mg/m³. The NOAEC for local portal of entry effects was the lowest tested concentration of 10 mg/m³.
Executive summary:

In a study carried out according to OECD Test Guideline 412, groups of 5 male and 5 female Wistar rats were exposed nose-only to 2-aminoethanol aerosol (with a vapour fraction; purity of the test substance: 99.93%) for 28 days, for 6 hours a day, on 5 days a week. The test concentrations were 0, 10, 50 or 150 mg/m³ (analysed concentrations: 10.2, 49.1 and 155.9 mg/m³; MMAD = 1.1 to 1.2 μm, with about 70% of the particles below 3 μm; the aerosol fraction was 0.5, 26.4 and 134.5 and the vapour fraction was 9.8, 22.7 and 21.4 mg/m³).

Effects on the larynx, trachea and lungs were found at 150 mg/m³ and above. There were no adverse systemic effects. The MCHC (mean corpuscular haemoglobin con­centration) was increased in male rats at 50 mg/m³ and above. As this increase was not accompanied by any other changes in red blood cell parameters, the effect was regarded as substance-related, but not as adverse. In addition, at 150 mg/m³, the triglyceride values of the males were reduced. This effect was not regarded as ad­verse because no concomitant findings were observed. The relative liver weights of all treated males were significantly decreased, but the decrease was not concentra­tion-dependent. This finding was not regarded as substance-related because there was no concentration–effect relationship or histopathological correlate.

Minimal or slight focal or multifocal hyperplasia of mucous cells was found in the bronchi of the lungs of all male rats and of 2 female rats of the group exposed to 150 mg/m³. The number of goblet cells was minimally or slightly increased in the affected bronchi.

Minimal to slight inflammation of the trachea was observed in 1 male after expo­sure to 10 mg/m³as well as in 4 males after exposure to 150 mg/m³. In addition, at the high concentration, minimal or slight focal squamous metaplasia was observed in the area of the carina in males. There were no treatment-related findings in the trachea of the females. However, 1 female control animal was found to have mini­mal focal inflammation of the trachea. The inflammation of the trachea observed in 1 male exposed to 10 mg/m³was not concentration-dependent; therefore, it was not induced by the substance.

At the entrance to the ventral pouch of the larynx (plane of section III), minimal (grade 1) focal squamous metaplasia was observed in 1 female at 50 mg/m³ as well as in 1 male and 2 females at 150 mg/m³. Minimal hyperplasia occurred in all males and in 4 females (concentration not specified). Minimal inflammation was found in 2 males and 3 females at 50 mg/m³as well as in all males and 4 females at 150 mg/m³.

At the base of the epiglottis in the larynx (plane of section I), submucosal inflam­mation characterized by infiltrates of granulocytes and lymphoid cells occurred in all males and females at 50 mg/m³and above. At 150 mg/m³, the inflammation was accompanied by degeneration of the submucosal glands. In addition, focal epithelial necrosis was observed at the base of the epiglottis in 4 males and 3 females of the high concentration group. In the same region, focal squamous cell metaplasia was observed in 3 male and 2 female rats at 50 mg/m³, and all animals were affected at 150 mg/m³. Minimal inflammation at the base of the epiglottis was detected in 1 female exposed to 10 mg/m³

The resulting local NOAEC for rats after 28-day exposure was 10 mg/m³, and the systemic NOAEC was 150 mg/m³.