2-hydroxy-3-phenoxypropyl acrylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 June 2015 - 22 July 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxy-3-phenoxypropyl acrylate

EC Number:

241-045-8

EC Name:

2-hydroxy-3-phenoxypropyl acrylate

Cas Number:

16969-10-1

Molecular formula:

C12H14O4

IUPAC Name:

2-hydroxy-3-phenoxypropyl acrylate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: 8 weeks old on the day of treatment
- Mean body weight at study initiation: 201 g (range: 191 g to 214 g)
- Fasting period before study: yes, during the night before treatment
- Housing: the animals were housed in threes from the same group in polycarbonate cages with stainless steel lids (Tecniplast 2154, 940 cm²)
- Diet: SSNIFF R/M-H pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 8 to 15 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 17 June 2015 to 22 July 2015.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: methylcellulose in solution at 0.5%

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Maximum dose-volume applied: 10 mL/kg

DOSAGE PREPARATION (if unusual): The test item was administered as a homogenous emulsion in the vehicle. The test item was mixed with the required quantity of vehicle.
Fresh dose formulations were prepared by the CiToxLAB France Pharmacy on the day of each administration and kept at room temperature prior to administration.

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: The starting dose-level was selected in agreement with the Sponsor. Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons.
After treatment at the starting dose-level, the next dose-levels were administered in a sequential manner, under the same conditions to different animals, based on the dose-levels indicated in the flow charts of OECD Guideline No. 423, 17th December 2001, which are equivalent to those of Commission Regulation (EC) No. 440/2008, B.1tris (30 May 2008).

Doses:

300 and 2000 mg/kg.

No. of animals per sex per dose:

3 females per treatment step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes (macroscopic).

Statistics:

no

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD0

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 unscheduled deaths occurred during the study.

Clinical signs:

other: No clinical signs were observed in animals given 300 mg/kg. At 2000 mg/kg, hunched posture was observed in 3/6 females on Day 1. This was associated with staggering gait and piloerection in one of them. These clinical signs were no longer observed from Da

Gross pathology:

There were no test item-related gross findings.

Other findings:

no

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 of 2-Hydroxy-3-phenoxypropyl acrylate was higher than 2000 mg/kg in rats.

Executive summary:

The objective of this study was to evaluate the potential acute toxicity of the test item following a single oral administration (gavage) to rats.

This study was conducted in compliance with OECD Guideline No. 423 and the principles of Good Laboratory Practices.

 

Methods

The test item was administered once by oral route (gavage) to three groups of three fasted female Sprague-Dawley rats under a dosage-volume of 10 mL/kg. The test item was prepared in a 0.5% solution of methylcellulose.

Since no relevant toxicity data were available for the estimation of a lethal dose-level and any existing data were taken into account by the Sponsor, the starting dose-level was 300 mg/kg for ethical reasons.After the first assay, the next higher dose-level of 2000 mg/kg was tested. Then, as no toxicity was observed at this higher dose-level, the results were confirmed in other females.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. Body weight was recorded on Day 1 and then on Days 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted for a macroscopic post-mortem examination.Macroscopic lesions were preserved in buffered formalin then destroyed at the finalization of the study report as no microscopic examination was performed.

 

Results

No unscheduled deaths occurred during the study and no clinical signs were observed in animals given 300 mg/kg.

At 2000 mg/kg, hunched posture was observed in 3/6 females on Day 1. This was associated with staggering gait and piloerection in one of them.These clinical signs were no longer observed from Day 2.

Body weight was unaffected by the test item treatment, when compared to CiToxLAB France historical control data.

There were no test item-related gross findings.

 

Conclusion

The oral LD₅₀of the test item was higher than 2000 mg/kg in rats.

Therefore, the test item should not be classified as toxic by oral route according to the criteria of CLP Regulation.