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Toxicological information

Basic toxicokinetics

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Administrative data

Endpoint:
basic toxicokinetics, other
Adequacy of study:
other information
Cross-referenceopen allclose all
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
other: Expert Statement
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Objective of study:
toxicokinetics
Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The purpose of the study was to determien the potential of toxicokinetic effects of the test substance based on its physico-chemical information.
GLP compliance:
not specified

Test material

Constituent 1
Reference substance name:
N,N-cyclohexyldimethylamine
IUPAC Name:
N,N-cyclohexyldimethylamine
Constituent 2
Chemical structure
Reference substance name:
Cyclohexyldimethylamine
EC Number:
202-715-5
EC Name:
Cyclohexyldimethylamine
Cas Number:
98-94-2
Molecular formula:
C8H17N
IUPAC Name:
N,N-dimethylcyclohexanamine
Constituent 3
Reference substance name:
DMCHA
IUPAC Name:
DMCHA
Details on test material:
- Name of test material (as cited in study report): DMCHA
- Molecular weight (if other than submission substance): 127
- Physical state: Liquid
- Boiling point (°C): 135-160
- Relative density: 0.85-0.89
- Vapour pressure: circa 440Pa at 26°C; 3.17 hPa at 21.5°C
- Water solubility: circa 1% at 20°C or 13.4 g/L
- Partition coefficient: log Kow 2.01 at 25°C
- Viscosity: 2.8 cST
Radiolabelling:
no

Test animals

Species:
other: Not relevant
Strain:
not specified
Sex:
not specified
Details on test animals or test system and environmental conditions:
Not relevant

Administration / exposure

Route of administration:
other: Not relevant
Vehicle:
not specified
Details on exposure:
Not relevant
Duration and frequency of treatment / exposure:
Not relevant
Doses / concentrations
Remarks:
Doses / Concentrations:
Not relevant
No. of animals per sex per dose / concentration:
Not relevant
Control animals:
not specified
Positive control reference chemical:
Not relevant
Details on study design:
In order to determine any toxicokinetic or toxicodynamic responses, the physico-chemical properties and toxicity responses were evaluated, in the absence of any specific study reports addressing metabolism, toxicokinetics or other ADME responses. The Toxicokinetic phase begins with exposure and results in a certain concentration of the ultimate toxicant at the target site (tissue dose). This concentration is dependent on the absorption, distribution, metabolism and excretion (ADME) of the substance. ADME describes the uptake of a substance into the body, its lifecycle within the body, and ultimately elimination via excretion:
ABSORPTION: how, how much, and how fast the substance enters the body;
DISTRIBUTION: reversible transfer of substances between various parts of the organism, i.e. body fluids or tissues;
METABOLISM: the enzymatic or non-enzymatic transformation of the substance of interest into a structurally different chemical (metabolite);
EXCRETION: the physical loss of the parent substance and/or its metabolite(s); the principal routes of excretion are via the urine, bile (faeces), and exhaled air.
Metabolism and excretion are the two components of ELIMINATION, which describe the loss of substance by the organism, either by physical departure or by chemical transformation.
DISPOSITION: The sum of processes following absorption of a chemical into the circulatory systems, distribution throughout the body, biotransformation, and excretion.
Details on dosing and sampling:
The moderate water solubility (13.4 g/L) of cyclohexyldimethylamine (DMCHA) was considered favourable for facilitating absorption within the gastro-intestinal tract. Another major route for toxicants to enter the body would be via lung absorption. The low LC50 value for acute inhalation toxicity indicates ready absorption through pulmonary membranes. The log Kow of 2.31 indicates that there is potential for DMCHA absorption across biological membranes and also for passive diffusion, supporting the apparent systemic absorption resulting in relatively high toxicity by oral and inhalation routes. It is not feasible to quantify absorption based on the available data, but the indications are that DMCHA is readily absorbable. Based on this information, it can be envisaged that once absorbed, DMCHA will be distributed throughout the body, across biological membranes such as the gastro-intestinal membrane and the membranes of the respiratory system.
Statistics:
Not relevant

Results and discussion

Preliminary studies:
No information provided

Toxicokinetic / pharmacokinetic studies

Details on absorption:
DMCHA is absorbed via oral, dermal and inhalation routes of exposure.
Details on distribution in tissues:
No information provided
Details on excretion:
No information provided

Metabolite characterisation studies

Details on metabolites:
No information provided

Any other information on results incl. tables

The moderate water solubility (13.4 g/L) of cyclohexyldimethylamine (DMCHA) was considered favourable for facilitating absorption within the gastro-intestinal tract. Another major route for toxicants to enter the body would be via lung absorption. The low LC50 value for acute inhalation toxicity indicates ready absorption through pulmonary membranes. The log Kow of 2.31 indicates that there is potential for DMCHA absorption across biological membranes and also for passive diffusion, supporting the apparent systemic absorption resulting in relatively high toxicity by oral and inhalation routes. It is not feasible to quantify absorption based on the available data, but the indications are that DMCHA is readily absorbable. Based on this information, it can be envisaged that once absorbed, DMCHA will be distributed throughout the body, across biological membranes such as the gastro-intestinal membrane and the membranes of the respiratory system.

The small molecular weight of the test substance (127g/mol) and Log Kow values do not satisfy the criteria set out in the guidance for indicating reduced dermal absorption, in fact the observed physiological changes following topical application indicate that mechanical bypassing of the dermis is feasible by corrosive action and tissue damage and that systemic exposure is likely following dermal exposure – the dermal LD50 is relatively low in two species (<400 mg//kg bw) indicating that dermal absorption is occurring. Given the similarity of median lethal doses following oral or dermal administration it is feasible to assume that dermal absorption approximates to the oral absorption value and a value of 100% should be considered for risk assessment purposes. 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): no data
The substance is likely to be bioavailable following oral, dermal and inhalation exposure.
Executive summary:

A theoretical assessment of the likely toxicokinetics of the substance is performed based on its physicochemical properties and limited toxicological data. The data indicate that the substance is likely to be bioavailable following oral, dermal and inhalation exposure. Simple comparison of the acute oral and dermal toxicity of the substance indicates that dermal absorption is likely to be extensive. The water solubility of the substance favours extensive and even systemic distribution via the circulatory system. QSAR indicates extensive metabolism; the production of a number of highly water-soluble metabolites favours urinary excretion and indicates that bioaccumulation is unlikely. In addition to this, the OECD Toolbox shows that the molecules satisfies Lipinski’s rule of 5, indicating it is likely to be bioavailable, and predicts a total of 15 hepatic metabolites resulting from N-dealkylation, N-oxidation and ring hydroxylation reactions.