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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
mechanistic studies
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Acceptable, well-documented report which meets basic scientific principles.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Cholinesterase inhibition in the acute toxicity of alkyl-substituted 2-Aminoethanols
Author:
Hartung R, Cornish HH
Year:
1968
Bibliographic source:
Toxicology and applied pharmacology, 12: 486-494
Reference Type:
secondary source
Title:
Patty's Industrial Hygiene and Toxicology.
Author:
Clayton G, Clayton FE
Year:
1994
Bibliographic source:
4th. Ed., Vol. 2

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The acute oral and intraperitoneal toxicity of a series of alkyl-substituted 2-aminoethanols was studied in relation to cholinesterase inhibition. Cholinesterase inhibition was conducted in vitro (brain and red cells), using a purified enzyme preparation derived from bovine erythrocytes. The level of in vitro inhibition was related to the number of carbon atoms attached on the nitrogenous head of the 2-aminoethanol molecule.
GLP compliance:
no
Type of method:
in vitro
Endpoint addressed:
neurotoxicity

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Butylethanolamine

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
no data

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
not specified
Details on exposure:
no data
Duration of treatment / exposure:
no data
Frequency of treatment:
no data
Post exposure period:
no data
Doses / concentrations
Remarks:
Doses / Concentrations:
650-1210 mg/kg bw
Basis:

Details on study design:
The enzyme activity was analyzed by a modification of the electrometric method of Michel (1949). This modification consisted of a titration of the buffer system with dilute acetic acid, so that the change in pH could be related to the amount of acetic acid liberated by the enzymatic hydrolysis of the acetylcholine substrate. During the analysis the pH varied from 7.7 to 7.3 . The brain and red cell cholinesterase levels were determined in rats which were sacrificed 10-15 minutes after receiving an intraperitoneal dose of the test substance. The whole rat brains were removed immediately after sacrifice and homogenized with an equal volume of physiological saline at 0°C. Red cells were separated from the plasma by centrifugation and washed twice with physiological saline prior to analysis.

Results and discussion

Details on results:
The acute oral and intraperitoneal toxicity of a series of alkyl-substituted 2-aminoethanols was studied in relation to cholinesterase inhibition. All the 2-aminoethanols studied inhibited cholinesterase in vitro in brain and red cells of rats that were treated intraperitoneally.
The data of this publication indicate that neutralized N-alkyl substituted 2-aminoethanols inhibit cholinesterase in vitro. Inhibition increases as the degree of substitiution and the molecular size of the nitrogenous head of the aminoethanol molecular increase. When the concentrations of substituted aminoethanols producing 50% inhibition in vitro are compared with their intraperitoneal LD50 doses on a molar basis, these two variables were found to correlate well on a statistical basis: for the test substance an inhibiting concentration of 15 mmol/Liter was found and correlated to an oral LD50 of 61.9 and and i.p. LD50 of 7.17 mmol/kg. The oral LD50 was taken from previous studies.

Applicant's summary and conclusion