RD 14156

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

This study was conducted between 22 October 2015 and 28 December 2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

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

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor Lot/Batch number 1004R17501


STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature and humidity


TREATMENT OF TEST MATERIAL PRIOR TO TESTING

- Final preparation of a solid: 2.0 g of test article were mixed with corn oil to a total volume of 10 ml. This mixture was mixed until visibly homogeneous (opaque yellow solution).

FORM AS APPLIED IN THE TEST (if different from that of starting material)

OTHER SPECIFICS:

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Raleigh NC
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: ~10 weeks
- Weight at study initiation: 198-208 g
- Fasting period before study: 16-20h
- Housing: individually housed in suspended stainless steel wire bottom cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: >5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 October 2015 To: 13 November 2015

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 2.0 mL
- Justification for choice of vehicle: solubility
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing: Animals were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology,

Results and discussion

Effect levels

Key result

Sex:

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:

All five female rats survived following a single 2000 mg/kg oral dose.

Clinical signs:

Abnormal physical signs of partially chewed food in pan liner and diarrhea were observed.

Body weight:

All five animals gained body weight by study termination. One animal lost weight between Days 7 and 14.

Gross pathology:

The gross necropsy of all animals revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LDso of RD 14156 is greater than 2000 mg/kg.

Executive summary:

Objective:

To determine the potential for toxicity of the test article when administered orally. This study was designed to comply with the standards set forth in the current EPA Health Effects Test Guidelines, OPPTS 870.1100, and in OECD Guidelines for the Testing of Chemicals, Guideline 425.

Method Synopsis:

Initially, a single female Sprague Dawley rat was dosed orally with RD 14156 at a dose level of 2000 mg/kg. Since the animal survived, four additional females were dosed at 2000 mg/kg. The rats were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination. All animals were examined for gross pathology. The potential for toxicity was based on the mortality response noted.

Summary:

All five female rats survived following a single 2000 mg/kg oral dose.

Abnormal physical signs of partially chewed food in pan liner and diarrhea were observed.

All five animals gained body weight by study termination.

One animal lost weight between Days 7 and 14.

The gross necropsy of all animals revealed no observable abnormalities.

Conclusion:

The oral LD50 of RD 14156 is greater than 2000 mg/kg.