DL-α-(aminomethyl)-p-hydroxybenzylic alcohol hydrochloride

Basic toxicokinetics

Administrative data

Endpoint:

basic toxicokinetics, other

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 April 2019

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Data source

Reference

Reference Type:

other:

Title:

Octopamine Hydrochloride- Assessment of Toxicokinetic behavior

Author:

C Smith

Year:

2019

Materials and methods

Objective of study:

toxicokinetics

Test guideline

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)

GLP compliance:

no

Remarks:

Not relevant for assessment

Test material

Test material information

1

Reference substance name:

DL-α-(aminomethyl)-p-hydroxybenzylic alcohol hydrochloride

EC Number:

212-216-4

EC Name:

DL-α-(aminomethyl)-p-hydroxybenzylic alcohol hydrochloride

Cas Number:

770-05-8

Molecular formula:

C8H11NO2.ClH

IUPAC Name:

4-(2-amino-1-hydroxyethyl)phenol hydrochloride

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Appearance: White to off white powder
Batch: D151-1710037
Purity/Composition: 99.8%
Test item storage: At room temperature protected from light
Stable under storage conditions until: 26 October 2019 (retest date)

Radiolabelling:

no

Results and discussion

Metabolite characterisation studies

Metabolites identified:

not measured

Any other information on results incl. tables

TOXICOKINETIC BEHAVIOUR

The substance is a white colored powder with physico-chemical properties which imply the risk of

particle inhalation to be minimal. Furthermore, the supporting toxicological information suggests

any inadvertent inhalation is unlikely to lead to an elevation in systemic toxicity. The substance was

identified to be an ocular irritant; the in vitro genotoxicity panel indicates that

there are no concerns for genotoxicity.

The results from a dermal irritation study, in conjunction with the molecular weight and log

Pow indicate limited absorption might occur via the dermis. Acute oral toxicity results showed the

LD50 to be >2000 mg/kg body weight, however the Oral (Gavage) Repeated Dose Toxicity Study in the

rat resulted in systemic effects resulting in death at the highest dose tested (1000 mg/kg bw/day) and a subsequent reduced dose (600 mg/kg bw/day), indicating gasto-intestinal absorption.

Absorption

The general physico-chemical properties of the substance : molecular weight, water solubility and

partition coefficient indicate that significant absorption by the oral route can be expected.

Supporting results from the Oral (Gavage) Repeated Dose Toxicity Study indicate

absorption from the gut.

Distribution

Information relating to the distribution of the substance 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 no evidence of test item metabolism as evidenced by hepatic histopathology from animals dosed in the Oral (Gavage) Repeated Dose Toxicity Study. However monoamine oxidase metabolism of octopamine is a known pathway, with deamination to hydroxymandelic acid.

Excretion

Following metabolism to hydroxymandelic acid, excretion routes are via kidneys and bile duct.

Applicant's summary and conclusion

Conclusions:

The available information suggests that absorption of substance from the gastrointestinal tract following oral ingestion is highly likely based upon the test items physico-chemical characteristics and relevent toxicity observed following oral dosing.
These characteristics together with the low volatility of the substance and particle size also indicate
absorption via inhalation exposure of test item to be unlikely. Given the lack of skin effects of the substance and unfavorable physico-chemico properties, limited dermal absorption can be expected. Any absorbed test material has the potential to undergo metabolism via monamine oxidase catalysed deamination and subsequent renal/bile clearance.