Methyl (R)-amino(4-hydroxyphenyl)acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

end on 09-APR-1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: study performed according to OECD guideline and GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Methyl (R)-amino(4-hydroxyphenyl)acetate

EC Number:

253-657-2

EC Name:

Methyl (R)-amino(4-hydroxyphenyl)acetate

Cas Number:

37763-23-8

Molecular formula:

C9H11NO3

IUPAC Name:

methyl (2R)-2-amino-2-(4-hydroxyphenyl)acetate

Details on test material:

- Name of test material (as cited in study report): FGHM
- Molecular formula (if other than submission substance): C9H11NO3
- Structural formula attached as image file (if other than submission substance): see Fig.
- Substance type: monoconstituent substance
- Physical state: powder
- Stability under test conditions: stability in propylene glycol not indicated
- Storage condition of test material: in refrigerator in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: approx. 6 weeks
- Weight at study initiation: 192g +/- 7g (males) and 161g +/- 6g (females) on day 1
- Fasting period before study: food was withheld overnight prior to each dosing until approximately 3-4 hours after administration of the test substance
- Housing: group housing of 5 animals per sex per cage in labelled polycarbonate cages containing purified sawdust as bedding material
- Diet: free access to standard pelleted laboratory animal diet
- Water: free access to tap water
- Acclimation period: at least 5 days before the start of the treatment uder laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature: 21 °C
- Humidity: 50%
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hrs dark / 12 hrs light

IN-LIFE DATES: data not available

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: data not available
- Justification for choice of vehicle: selected based on a pre-test

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

6250 mg/kg bw (1 x 3750 mg/kg bw and 1 x 2500 mg/kg bw within 24 hours starting on day 1)

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> mortality / viability: twice daily
> body weights: day 1, 8 and 15
> clinical signs: at periodic intervals on the days of dosing, and once daily thereafter
- Necropsy of survivors performed: yes

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 6 250 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

No mortality occured.

Clinical signs:

other: Hunched posture and uncoordinated movements were noted in the majority of animals. These symptoms have disappeared in all animals by day 3. Salivation was observed in 1 male and 1 female immediately after the second treatment. This finding is occasionnaly

Gross pathology:

No abnormalities were found at macroscopic post-mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

oral gavage LD50 of HPGM (FGHM) > 6250 mg/kg bw

Executive summary:

In an acute oral toxicity study (OECD 401, GLP), a group of fasted, 6 week old Wistar rats (5 males and 5 females) were given an oral dose of HPGM (FGHM) propylene glycol at dose of 6250 mg/kg bw and observed for 14 days.

 

Oral LD50 Males/Females > 6250 mg/kg bw (limit test)

 

No mortality occured.

Hunched posture and uncoordinated movements were noted in the majority of animals. These symptoms have disappeared in all animals by day 3.

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

No abnormalities were found at macroscopic post-mortem examination of the animals.

 

Based on EC criteria for classification of dangerous substances (DSD directive and CLP regulation), HPGM (FGHM) is not classified as dangerous by acute oral administration.