Methyl (R)-2-(4-hydroxyphenoxy)propionate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not reported

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

1984

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)-2-(4-hydroxyphenoxy)propionate

EC Number:

411-950-4

EC Name:

Methyl (R)-2-(4-hydroxyphenoxy)propionate

Cas Number:

96562-58-2

Molecular formula:

C10H12O4

IUPAC Name:

methyl (2R)-2-(4-hydroxyphenoxy)propanoate

Test material form:

solid

Details on test material:

- Appearance: Brown solid
- Storage conditions of test material: Refrigerator

Test animals

Species:

rat

Strain:

Wistar

Remarks:

CHBB: THOM (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females (if applicable) nulliparous and non-pregnant: Not specified
- Age at study initiation: Young adult animals
- Weight at study initiation: Animals of comparable weight between 150 and 300 g (± 20 % of the mean weight)
- Fasting period before study: Yes; the animals were given no feed for at least 16 hours before administration, but water was available ad libitum
- Housing: The animals were singly housed in stainless steel wire mesh cages. There was no bedding in the cages but sawdust was available in the waste trays.
- Diet: ad libitum
- Water: ad libitum access to tap water
- Acclimation period: At least one week

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 24 °C
- Humidity: 30 to 70 % (relative)
- Air changes: Not specified; the room was air conditioned
- Photoperiod: 12 hours of light/12 hours of darkness (06:00 to 18:00 light)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Remarks:

DAB 9

Details on oral exposure:

DOSING SOLUTION
The test material was administered as an emulsion (application of cooled down test material preparation to body temperature).
The stability of the test material in olive oil DAB 9 over a time period of 4 hours was confirmed by analysis. A concentration control analysis was performed and values were found to be about 12 % higher than expected. Homogeneity of the preparation was provided by stirring and heating at about 70 °C.

VEHICLE
- Concentration in vehicle: 44 g/100 mL
- Justification for choice of vehicle: The test material was poorly soluble in water

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

Doses:

2200 mg/kg of bodyweight

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights were determined shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period). Recording of signs and symptoms took place several times on the day of administration and at least once each workday for the individual animals. A check was made twice each workday and once on Saturdays, Sundays and on public holidays for general observations and for any dead or moribund animals.
- Necropsy of survivors performed: Yes. Necropsy with gross pathological examination was performed on the last day of the observation period, with withdrawal of food at least 16 hours before death with CO2.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 200 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

There were no mortalities observed.

Clinical signs:

other: There were no clinical signs observed for any of the animals throughout the study.

Gross pathology:

No pathology findings were noted in any of the animals.

Any other information on results incl. tables

Table 1. Individual body weights

Dose (mg/kg)	Males	Day 0	Day 7	Day 13
2200	Cage 949	185	257	281
	Cage 950	187	263	288
	Cage 951	185	250	282
	Cage 952	191	250	278
	Cage 953	190	244	266
Dose (mg/kg)	Females	Day 0	Day 7	Day 13
2200	Cage 954	180	212	217
	Cage 955	182	213	227
	Cage 956	183	213	225
	Cage 957	183	212	227
	Cage 958	179	198	212

Applicant's summary and conclusion

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study, the LD50 was greater than 2200 mg/kg body weight (males and females).

Executive summary:

A study was conducted to investigate the acute oral toxicity of the test material in accordance with the standardised guidelines OECD 401 and EU Method B.1 under GLP conditions.

A group of ten fasted animals (five males and five females) was given a single oral dose of the test material prepared in olive oil DAB 9 at a dose level of 2200 mg/kg of bodyweight by gavage. Over a 14 day observation period, the animals were monitored for mortality, signs of toxicity and body weight gain. At the end of the observation period animals were sacrificed and subjected to necropsy with gross pathological examination.

No mortality occurred and no signs of toxicity were noted at this dose level. The expected body weight gains were observed throughout the course of the study. No abnormalities were noted at necropsy.

Under the conditions of this study, the LD50 was greater than 2200 mg/kg body weight (males and females).