N'-(ethylcarbonimidoyl)-N,N-dimethylpropane-1,3-diamine monohydrochloride

Endpoint summary

Link to relevant study record(s)

Reference

Endpoint:

basic toxicokinetics in vitro / ex vivo

Type of information:

other: In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behavior has been conducted to the extent that can be derived from the relevant available information.

Adequacy of study:

key study

Study period:

The assessment was conducted in july 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Relevant studies were reviewed by a qualified toxicologist with a view to fulfilling the requirements of Annex VIII (8.8).

Objective of study:

toxicokinetics

Qualifier:

no guideline followed

Principles of method if other than guideline:

In accordance with REACH Annex VIII (8.8) an assessment of toxicokinetic behaviour has been conducted to the extent that can be derived from the relevant available information.The assessment is based on the Guidance on information requirements and chemical safety assessment R.7c:
Endpoint specific guidance (ECHA, November 2014)

Radiolabelling:

no

Metabolites identified:

yes

Details on metabolites:

EDAC is known to be unstable in pH ranges outside of neutral pH 7. The main known metabolite of EDAC is EDAU

EDAC is a white to to off white powder. EDAC is very hydrolytic and unstable with the ½ life of 1.5 hrs at pH7 where it is converted into the metabolite 1-ethyl-3-(3-dimethylaminopropyl) urea. Physico-chemical properties such as log Kow and vapour pressure imply the risk of particle inhalation would be minimal. However, based on the water solubility and particle size any vapour could potentially be absorbed. Furthermore, the supporting toxicological information suggests any inadvertent inhalation may lead to an elevation in systemic toxicity as acute dermal and oral effects were detected and the substance is considered to be STOT RE 2. EDAC was identified to be a kin and ocular irritant; the in vitro genotoxicity panel indicates that there are limited concerns for genotoxicity, with negative effects seen in the in-vivo studies.

The results from a single dermal dose toxicity study (irritation) in conjunction with the molecular weight indicate that absorption occurs via the dermis with the LD50 value of between 200-1000mg/kg. Acute oral toxicity results showed the LD50 to be 500 mg/kg body weight, and the Oral (Gavage) Repeated Dose Toxicity Study in the rat resulted in any adverse toxicological findings at the highest dose tested of 300mg/kg/day, based upon these findings, absorption form the Gastrointestinal tract and dermis can be anticipated.

Absorption

The general physico-chemical properties of EDAC including the molecular weight and log Pow and toxicological findings would indicate that significant absorption is possible of the metabolite EDAU.

Distribution

Information relating to the distribution of EDAU is limited; however, the chemical characteristics and findings from the Oral (Gavage) Repeated Dose Toxicity Study implies systemic distribution would most likely occur via the serum following oral administration and gastric absorption.

 

Metabolism

There is limited evidence of test item or metabolite influenced hepatic metabolism from the Oral (Gavage) Repeated Dose Toxicity Study.

 

Excretion

The most plausible route of clearance for relatively highly soluble chemicals would be by transfer of test material and/or metabolites from the plasma leading to clearance of any metabolic breakdown products primarily via the urine.

Conclusions:

The available information demonstrates that absorption of substance from the gastrointestinal tract following oral ingestion occurs given the test items physico-chemical characteristics.
These characteristics together with the observed systemic toxicity and acute dermal toxicity also indicate absorption via dermal exposure of test item occurs in addition to oral adsorption. Absorption via the inhalation route is not expected to occur based on the very low vapour pressure.
The substance is not expected to bioacumulate based on the log Kow value of -2.98

Key value for chemical safety assessment

Bioaccumulation potential:

low bioaccumulation potential

Absorption rate - oral (%):

50

Absorption rate - dermal (%):

100

Absorption rate - inhalation (%):

100