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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

18 August 1992 to 01 September 1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

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: Tan or brown solid
- Storage conditions: In the dark at ambient temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Remarks:

ICO: OFA-SD (IOPS Caw)

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: Approximately 8 weeks old
- Weight at study initiation: Mean body weight of 271 ± 3 g for the males and 229 ± 4 g for the females
- Fasting period before study: No
- Housing: The animals were housed in groups of 4 to 7 animals of the same sex per cage during the acclimatisation period and individually during the study. They were housed in polycarbonate cages throughout the study (48 x 27 x 20 cm during the acclimatisation period and 35.5 x 23.5 x 19.3 cm during the study). The cages were covered with a stainless steel lid containing food and a water bottle. Sifted and dusted sawdust was provided as litter.
- Diet: ad libitum with a certified pelleted diet
- Water: ad libitum access to tap water filtered by a 0.22 micron filter membrane and contained in water bottles
- Acclimation period: At least 5 days before treatment

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 50 ± 20 % (relative)
- Air changes: Not specified; the air was non-recycled and filtered
- Photoperiod: 12 hours of light/12 hours of darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal area; the day before treatment, the dorsal region of each animal was clipped using an electric clipper on an area of 6 x 8 cm.
- % coverage: Approximately 10 % (5 x 6 cm for the females and 5 x 7 cm for the males) according to Meeh's formula
- Type of wrap if used: The test material and the gauze patch were held in contact with the skin by means of an adhesive hypoallergic aerated semi-occlusive dressing attached to a restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No; no residual test material was observed at removal of the dressing
- Time after start of exposure: The dressing was removed after 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: Yes; the test material was ground down to a fine dust and applied on a hydrophilic gauze patch pre-moistened with 2 mL of water

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

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: The animals were observed frequently after application of the test material and at least once a day for 14 days in order to determine the reversibility or irreversibility of any clinical signs. The animals were checked frequently for mortality and signs of morbidity just after administration of the test material and at least twice a day during the 14-day observation period. The animals were weighed individually before application of the test material and then on days 5, 8 and 15. The body weight gain of the treated animals was compared to a reference curve of control animals with the same initial weight.
- Necropsy of survivors performed: Yes. On the 15th day, the animals were sacrificed after CO2 inhalation in excess and a necropsy was performed. After opening the abdominal and thoracic cavities a macroscopic examination of the main organs was performed: digestive tract, heart, kidneys, liver, lungs, pancreas, spleen and any other organ with obvious abnormalities.
- Other: Due to the absence of macroscopic lesions, no organ samples were taken and no histological examination was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No deaths occurred during the observation period.

Clinical signs:

other: No clinical signs were observed during the study.

Gross pathology:

Macroscopic examination of the main organs of the animals at the end of the study revealed no apparent abnormalities.

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 2000 mg/kg body weight (males and females).

Executive summary:

A study was conducted to investigate the acute dermal toxicity of the test material in accordance with the standardised guidelines OECD 402 and EU Method B.3 under GLP conditions.

The undiluted test material ground down to a fine dust was prepared on a compress moistened with water at a limit dose of 2000 mg/kg and then applied to the skin of 10 Sprague-Dawley rats (5 males and 5 females). The material remained on the skin for 24 hours under a semi-occlusive dressing.

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.

The general behaviour and body weight gain of the animals were not affected by treatment. No deaths occurred at 2000 mg/kg. Macroscopic examination at the end of the study revealed no abnormalities.

Under the conditions of this study, the LD50 was greater than 2000 mg/kg body weight (males and females).