D-α-methylbenzylamine

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics

Type of information:

other: Expert statement

Adequacy of study:

key study

Study period:

2013-03-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Expert statement in the absence of toxicokinetic studies was performed with the Racemat (DL-alpha-methylbenzylamine). Read across is done to D-alpha-methylbenzylamine, as the substance is expected to behave comparable to the racemat with regard to toxicokinetic properties. For read-across justification please refer to IUCLID section 13.

Data source

Reference

Reference Type:

other: Expert statement

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Objective of study:

toxicokinetics

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Expert statement

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

DL-α-methylbenzylamine

EC Number:

210-545-8

EC Name:

DL-α-methylbenzylamine

Cas Number:

618-36-0

IUPAC Name:

1-phenylethanamine

Test material form:

other: liquid

Test animals

Species:

other: Expert statement

Strain:

other: Expert statement

Details on test animals or test system and environmental conditions:

Not applicable.

Administration / exposure

Route of administration:

other: Expert statement

Vehicle:

other: Expert statement

Details on exposure:

Not applicable.

Duration and frequency of treatment / exposure:

Not applicable.

Doses / concentrations

Remarks:

Doses / Concentrations:
Not applicable.

No. of animals per sex per dose / concentration:

Not applicable.

Positive control reference chemical:

Not applicable.

Details on study design:

Not applicable.

Details on dosing and sampling:

Not applicable.

Statistics:

Not applicable.

Results and discussion

Preliminary studies:

Not applicable.

Toxicokinetic / pharmacokinetic studies

Details on absorption:

After oral administration DL-α-methylbenzylamine is assumed to dissolve in the gastrointestinal fluids and absorption via aqueous pores or carriage across membranes with the bulk passage of water might occur as indicated by the water solubility. In addition, absorption of the substance via passive diffusion might be favoured due to the log Pow value of 1.31. The LD50 evaluated in an oral acute toxicity study indicates that the compound becomes bioavailable after oral administration.
Both, penetration into the stratum corneum and transfer into the epidermis is likely to occur based on the molecular weight, the water solubility and the log Pow value of the test substance. Due to the strong basic properties of DL-α-methylbenzylamine tissue destruction was observed at the sites of first contact in the acute oral toxicity study as well as in the human skin model resulting in an enhanced oral and dermal absorption.
Due to the vapour pressure of 0.56 hPa the test substance might become available for inhalation. As indicated by the molecular weight and the physico-chemical properties the test substance might cross the respiratory tract epithelium by passive diffusion or active transport via aqueous pores.
Taken together, experimental data and physico-chemical properties indicate bioavailability of the test substance via oral, dermal and inhalation route. Regarding absorption no difference between the racemic mixture and the enantiomers is expected due to identical physical properties.

Details on distribution in tissues:

As D-and L-α-methylbenzylamine are small, water-soluble molecules, a wide distribution of the substances in the organism is expected. Cellular uptake is assumed due to their slight lipophilic properties. This assumption is supported by the adverse effects observed in all lobes of the lung and in the liver after oral administration. Extensive bleedings in the glandular stomach are attributed to the strong basic properties of the substance.
Based on the log Pow value and the water solubility of the test substance no bioaccumulation is expected.

Details on excretion:

D- and L-α-methylbenzylamine and its potential oxidised or conjugated metabolites are estimated to be renal excreted due to their low molecular weights and high water solubility.

Metabolite characterisation studies

Details on metabolites:

The test substance might be deaminated to ammonia and acetophenone, which in turn might be reduced to 1-phenylethanol. Oxidation or conjugation of the side chain leads to 1-phenyl-1,2-ethanediol, mandelic acid and phenylglyoxylic acid. Ammonia is expected to be cleared by standard physiological pathways.
DL-α-methylbenzylamine and its metabolites are expected not to be genotoxic and metabolic activation is unlikely to occur. Metabolic turnover might be varying between the D- and L-form of the substance.

Bioaccessibility (or Bioavailability)

Bioaccessibility (or Bioavailability) testing results:

Experimental data and physico-chemical properties indicate bioavailability of the test substance via oral, dermal and inhalation route. Regarding absorption no difference between the racemic mixture and the enantiomers is expected due to identical physical properties.