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Administrative data

Description of key information

The oral LD50 of RD14156 based upon read-across to an analogous substance is greater than 2000 mg/kg.

The dermal LD50 of RD 14156 based upon read-across to an analogous substance

is greater than 2000 mg/kg of body weight in rats.

A study for acute inhalation toxicity does not need to be conducted because inhalation is not anticipated to be a significant route of exposure based on the low vapour pressure and physical form of the substance (waxy solid/powder).

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:
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
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
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
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:
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
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,
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.
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One study available conducted under GLP and in accordance with an approriate test guideline.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
.Not applicable. No study available.

Acute toxicity: via dermal route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
07 July 2016 - 21 July 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: DOT 49 CFR 173.132(b)(2)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
Approximately 24 hours prior to application of the test article, the dorsal area of the animals were clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact. A single dose (2000mg/kg) of the test material, moistened with 1.0 ml of corn oil, was applied and remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test material was removed by gently washing with corn oil.


Duration of exposure:
24 hours
Doses:
2000 mg/kg of body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Dermal responses were recorded at 24 hours post-dosing and on Day 14. Animals were observed for mortality, toxicity and pharmacological effects at one and four hours post-dosing and once daily thereafter for 14 days. Body weights were recorded pre-test, weekly, and at termination. All animals were examined for gross pathology.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
Immediately following unwrapping, very slight erythema and edema were absent. By Day 14, erythema and edema were absent.
Body weight:
All ten animals gained body weight by study termination.
Gross pathology:
The gross necropsy revealed no observable abnormalities.
Other findings:
No abnormal physical signs were observed.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The dermal LD50 of RD 14153 is greater than 2000 mg/kg of body weight in rats.
Endpoint:
acute toxicity: dermal
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read across from K1 study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
Approximately 24 hours prior to application of the test article, the dorsal area of the animals were clipped free of hair. The prepared site was approximately 10% of the body surface and remained intact. A single dose (2000mg/kg) of the test material, moistened with 1.0 ml of corn oil, was applied and remained in contact with the skin for 24 hours at which time the wrappings were removed. Residual test material was removed by gently washing with corn oil.


Duration of exposure:
24 hours
Doses:
2000 mg/kg of body weight
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Dermal responses were recorded at 24 hours post-dosing and on Day 14. Animals were observed for mortality, toxicity and pharmacological effects at one and four hours post-dosing and once daily thereafter for 14 days. Body weights were recorded pre-test, weekly, and at termination. All animals were examined for gross pathology.
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other:
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed.
Clinical signs:
Immediately following unwrapping, very slight erythema and edema were absent. By Day 14, erythema and edema were absent.
Body weight:
All ten animals gained body weight by study termination.
Gross pathology:
The gross necropsy revealed no observable abnormalities.
Other findings:
No abnormal physical signs were observed.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
The dermal LD50 of RD 14153 is greater than 2000 mg/kg of body weight in rats.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
One study available conducted under GLP and in accordance with an approriate test guideline.

Additional information

In a study to determine the acute toxicity of an analogous substance via oral administration all animals survived a single dose of 2000 mg/kg bodyweight. there were no ablnormal physical signs, all five rats gained in bodyweight and gross pathology of all animals revealed no observable abnormalities.

In a study to determine the acute toxicity of an analogous substance via oral administration All animals survived following a 24 -hour dermal exposure at 2000 mg/kg. No abnormal physical signs were observed. All ten animals gained body weight by study termination. The gross necropsy revealed no observable abnormalities. Immediately following unwrapping, erythema and edema were absent to very slight. By Day 14, erythema and edema were absent.

Justification for classification or non-classification

An analogous substance has been tested for acute oral toxicity and the LD50 was determined to be greater than 2000 mg/kg.

An analogous substance has been tested for acute dermal toxicity and the LD50 was determined to be greater than 2000 mg/kg.

In accordance with the classification criteria described in CLP Regulation 1272/2008 the substance is not classified for acute oral or acute dermal toxicity.