Registration Dossier

Administrative data

Description of key information

The acute oral LD50 of the test substance is greater than 2,000 mg/kg of body weight in female rats.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no
Species:
rat
Strain:
Fischer 344
Sex:
female
Details on test animals 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
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.
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:
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 respiration and piloerection. Clinical signs for the surviving animals included reduced fecal volume, red facial staining, ano-genital staining, red ocular discharge, hypoactivity, hunched posture, irregular respiration and/or clear oral discharge. However, the animals recovered from these signs by Day 7 and appeared active and healthy for the remainder of the study.
Body weight:
900 mg/kg Dose Level (2 animals) - both animals gained weight during the 14 day observation period
2,000 mg/kg Dose Level (4 animals) - Although two animals lost weight, one animal gained body weight throughout the study.
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

No additional information available.

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
GLP/Guideline study

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The acute oral LD50 of the test substance is >2000 mg/kg in female rats.


Justification for selection of acute toxicity – oral endpoint
Newest study conducted under GLPs and guidelines.

Justification for classification or non-classification

There is no justification for classification based on data from available studies.