(2R)-4-hydroxybutan-2-aminium (2S)-hydroxy(phenyl)acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

(R)-3-Ammonium-1-hydroxybutyl (S)-mandelat

IUPAC Name:

(R)-3-Ammonium-1-hydroxybutyl (S)-mandelat

Constituent 2

Reference substance name:

(2R)-4-hydroxybutan-2-aminium (2S)-hydroxy(phenyl)acetate

EC Number:

810-156-9

Cas Number:

1236049-43-6

Molecular formula:

C4H11NO*C8H8O3

IUPAC Name:

(2R)-4-hydroxybutan-2-aminium (2S)-hydroxy(phenyl)acetate

Details on test material:

- Name of test material (as cited in study report): (R)-3-Ammonium-1-hydroxybutyl (S)-mandelat
- Physical state: solid / white
- Analytical purity: 99.8 %
- Lot/batch No.: 15-0010

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: Young adult animals (female animals approx. 10 weeks)
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight)
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: single housing, Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days before the beginning of the experimental phase

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 30 - 70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Details on study design:

- Duration of observation period following administration: 14 days
- Other examinations performed: clinical signs, body weight, mortality and pathology

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

No clinical signs were observed during clinical examination.

Body weight:

The body weights of the surviving animals increased within the normal range in the first observation week with one exception. One female animal of the second test group showed stagnation of body weight. During the second week, in four out of six animals (two in each test group) stagnation of body weight was observed, while the two remaining animals revealed a normal body weight increase. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.

Gross pathology:

There were no macroscopic pathological findings in all animals sacrificed at the end of the observation period.

Any other information on results incl. tables

Mortality
Dose (mg/kg bw):	2000	2000
Sex:	female	female
Administration:	1	1
No. of animals	3	3
Mortality (animals)	No mortality	No mortality

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study the median lethal dose of (R)-3-Ammonium-1-hydroxybutyl (S)-mandelat after oral administration was found to be greater than 2000 mg/kg bw in rats.