2-aminoethanol

Respiratory sensitisation

Administrative data

Endpoint:

respiratory sensitisation, other

Remarks:

In vivo / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Effects of inhaled monoethanolamine on bronchoconstriction

Author:

Kamijo Y., Hayashi I., Ide A., Yoshimura K., Soma K., Majima M.

Year:

2009

Bibliographic source:

J. Appl. Toxicol. 2009; 29: 15–19

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Measurement of bronchoconstriction (Pao) and analysis of Histamine in Bronchoalveolar Lavage Fluid (BALF) in the guinea pig in vivo. Measurement of contraction of the guinea pig trachea ex vivo, following exposure to the test substance and the test substance in combination with other agents known to affect respiratory function.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-aminoethanol

EC Number:

205-483-3

EC Name:

2-aminoethanol

Cas Number:

141-43-5

Molecular formula:

C2H7NO

IUPAC Name:

2-aminoethanol

Test material form:

liquid

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: SLC, Hamamatsu, Japan
- Weight at study initiation: 350–450 g

Test system

No. of animals per dose:

4

Details on study design:

Animal Preparation:
Animals were anesthetized with pentobarbital sodium (50 mg/kg, i.p.) and placed on a heated blanket to maintain body temperature at approximately 37 °C. The trachea was cannulated, and the lungs were ventilated artificially with room air at 70 strokes/min with a tidal volume of 10 mL/kg body weight. Airway opening pressure (Pao) was monitored using a pressure transducer positioned on a side arm of the tracheal cannula to provide an index of the change in tracheobronchial resistance to airflow. Aerosols of solutions were inhaled through the tracheal cannula after nebulization while drugs were injected intravenously through a catheter inserted into the jugular vein. The Pao was recorded with a polygraph. Body temperature was monitored with a probe inserted into the rectum.

Determination of the Pao Increase Induced by Aerosols of MEA Solution or Potassium Hydroxide Solution:
Pao increase was determined after inhalation of an aerosol of 0.1 mL/kg of 3.3% test substance solution (pH 12.0) via the tracheal cannula. The Pao increase was calculated as the difference between the baseline value and the maximum-response value after treatment of the group with the test substance (n = 4). As control, an aerosol of potassium hydroxide (KOH) solution at the same pH was inhaled. In the same manner as for the test substance group, control group (n = 4) underwent measurement of the Pao increase after inhalation of an aerosol of 0.1 mlL/kg of 0.056% KOH solution (pH 12.0) via tracheal cannula.

Furthermore:
- Pao Increase induced by inhaled MEA after administration of Atropine Sulfate, Diphenhydramine Hydrochloride, FK-3657, or Pranlukast was determined. Acetylcholine, histamine, bradykinin and cysteinyl leukotriene are well-known mediators inducing bronchoconstriction. To investigate involvement of these mediators in MEA-induced bronchoconstriction, an aerosol of MEA solution was inhaled after administration of agents that suppress actions of these mediators.
- For further investigation of involvement of acetylcholine in MEA induced bronchoconstriction, a group of guinea pigs (n = 4) inhaled an aerosol of MEA solution after administration of a carbamate, acetylcholinesterase inhibitor, which would enhance the action of acetylcholine.
- To assess the role of histamine in MEA-induced bronchoconstriction, histamine in bronchoalveolar lavage fluid (BALF) was measured in another group of guinea pigs (n = 4) during MEA-induced bronchoconstriction.
- To investigate participation of the agonistic effect of MEA at histamine-H1 receptors or muscarinic receptors in MEA-induced bronchoconstriction, contraction of epithelially denuded trachea was measured in vitro during superfusion with MEA after previous exposure to a histamine-H1 receptor antagonist or a muscarinic receptor antagonist.

Results and discussion

Results:

An aerosol of 3.3% MEA solution (0.1 mL kg−1) delivered via the trachea significantly induced bronchoconstriction. More potently than did an aerosol of KOH solution (0.1 mL/kg) at the same pH.
MEA-induced bronchoconstriction was significantly suppressed by premedication with an intravenous injection of atropine sulfate or diphenhydramine, but was not suppressed by premedication with intravenous administration of FK-3657 or enteral administration of pranlukast.
MEA-induced bronchoconstriction was not enhanced by premedication with an intravenous injection of neostigmine.
In BALF obtained during MEA-induced bronchoconstriction, the histamine concentration was not significantly higher than in BALF obtained during KOH-induced bronchoconstriction or in BALF after inhalation of physiologic saline.
Contraction of epithelially denuded trachea during superfusion with MEA (10 mM) was suppressed by pretreatment with superfusion of pyrilamine maleate (10 and 100 μM), a histamine-H1 receptor antagonist, in a dose dependent manner. Contraction of the epithelially denuded trachea during superfusion with MEA (10 mM) was suppressed by pretreatment with superfusion of atropine sulfate (10 and 100 μM), a muscarinic receptor antagonist, in a dose dependent manner.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification