2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, phosphate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP/Guideline Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, phosphate

EC Number:

258-053-2

EC Name:

2-Propenoic acid, 2-methyl-, 2-hydroxyethyl ester, phosphate

Cas Number:

52628-03-2

Molecular formula:

C6 H10 O3 . x H3 O4 P

IUPAC Name:

2-(methacryloyloxy)ethyl phosphate

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): Reaction product of 2-Hydroxyethyl methacrylate (HEMA) with Polyphosphoric Acid (PPA)
- Physical state: clear yellow liquid
- Lot/batch No.: A022C73001
- Expiration date of the lot/batch: August 20, 2014
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories, Inc., Frederick, MD
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 134-148 grams at experimental start.
- Fasting period before study: overnight
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors
- Diet (e.g. ad libitum): Harlan Teklad Certified Global 16% Protein Rodent Diet® #2016C. The diet was available ad libitum, except during fasting.
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Acclimation period: 21-34 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-22ºC
- Humidity (%): 40-70%
- Air changes (per hr): 13 or 14
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: October 16 – November 12, 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Based on an estimate of the LD50 supplied by the Sponsor (1,800 mg/kg and an assumed sigma of 0.3), a
Main Test was conducted using a default starting dose level of 900 mg/kg.

Doses:

900 mg/kd or 2000 mg/kg

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual body weights of the animals were recorded prior to test substance administration (initial) and again on Days 7 and 14 (termination) following dosing or after death. The animals were observed for mortality, signs of gross toxicity, and behavioral changes during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing or until death occurred.
- Necropsy of survivors performed: yes

Statistics:

The Acute Oral Toxicity (Guideline 425) Statistical Program was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal dosed at 2000 mg/kg died within one day of test substance administration. All other animals survived until necropsy.

Clinical signs:

other: 900 mg/kg Dose Level (2 animals) - There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. 2,000 mg/kg Dose Level (4 animals) - Prior to death, one animal was hypoactive and exhibited hunched posture, irregular respirat

Gross pathology:

900 mg/kg Dose Level (2 animals) - No gross abnormalities were noted for these animals when necropsied at the conclusion of the 14-day observation period.
2,000 mg/kg Dose Level (4 animals) - Gross necropsy of the decedent revealed moderately distended stomach, filled with dark blackish liquid. No gross abnormalities were noted for any of the euthanized animals when necropsied at the conclusion of the 14-day observation period.

Other findings:

none

Any other information on results incl. tables

No additional information available.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category V

Remarks:

Migrated information Criteria used for interpretation of results: other: UN GHS

Conclusions:

Under the conditions of this study and according to OECD Guideline 425, the acute oral LD50 of the test substance is greater than 2,000 mg/kg of
body weight in female rats, because there were three consecutive survivors at 2,000 mg/kg.

Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with female Fischer 344 rats to determine the potential forReaction product of 2-Hydroxyethyl methacrylate (HEMA) with Polyphosphoric Acid (PPA)to produce toxicity from a single dose via the oral route. Under the conditions of this study and according to OECD Guideline 425, the acute oral LD₅₀ of the test substance is greater than 2,000 mg/kg of body weight in female rats, because there were three consecutive survivors at 2,000 mg/kg.