Cyclohexyldimethylamine

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics, other

Adequacy of study:

other information

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Objective of study:

toxicokinetics

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

Radiolabelling:

no

Species:

other: Not relevant

Strain:

not specified

Sex:

not specified

Details on test animals or test system and environmental conditions:

Not relevant

Route of administration:

other: Not relevant

Vehicle:

not specified

Details on exposure:

Not relevant

Duration and frequency of treatment / exposure:

Not relevant

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

Preliminary studies:

No information provided

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

Details on metabolites:

No information provided

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. 

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.

Description of key information

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.

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

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.