Registration Dossier

Administrative data

Description of key information

The oral LD50 of RD14153 is greater than 2000 mg/kg.

The dermal LD50 of RD 14153 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, flakes).

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:
The study was conducted between 22 October 2015 and 13 November 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
not specified
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
not specified
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Sponsor Batch/Lot no. PW2
- Expiration date of the lot/batch:
- Purity test date:06 October 2015

RADIOLABELLING INFORMATION (if applicable)
- Radiochemical purity:
- Specific activity:
- Locations of the label:
- Expiration date of radiochemical substance:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material:
- Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

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 and environmental conditions:
TEST ANIMALS
- Source: Charles River, Raleigh NC, USA
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 9 wks
- Weight at study initiation: 188 - 208 g
- Fasting period before study: yes, 16-20h
- Housing: individually in 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): controlled but not reported
- Humidity (%): controlled but not reported
- 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: 2.0 g/10 mL
- Amount of vehicle (if gavage): 2.0 mL
- Justification for choice of vehicle: to assist dosing by gavage
- Lot/batch no. (if required):
- Purity:

MAXIMUM DOSE VOLUME APPLIED: 2.0 mL/rat

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:Observed at 15 min, 1, 2 and 4 h and then once daily for 14 days. Bodyweights recorded pretest, weekly and at termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
other: pharmacological effects
Preliminary study:
One female rate dosed at 2000 mg/kg - No adverse effects.
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:
None
Clinical signs:
None
Body weight:
All five animals gained weight by study termination
Gross pathology:
Gross necropsy of all animals revealed no observable abnormalities
Interpretation of results:
other: The oral LD50 of RD14153 is >2000 mg/kg body weight
Conclusions:
The oral LD50 of RD14153 is greater than 2000 mg/kg.
Executive summary:

The study was designed to examine the potential toxicity of RD14153 when administered orally to Sprague-Dawley rats. the study was conducted according to the guidelines OECD 425 and OPPTS 870.1100.

Initially a single female rat was dosed orally with RD14153 at 2000 mg.kg bodyweight. The animal survived and subsequently 4 further femae rats were dosed at 2000 mg/kg bodyweight.The rats were observed at 15 mins 1, 2 and hours post dose and once daily for toxicity and pharmacological effects. All animals were observed twice daily for mortality. Bodyweights were recorded immediately pre-test, weekly and at termination.All animals were examined for gross pathology.

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.

The oral LD50 of RD14153 is greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
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
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
1 (reliable without restriction)
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Sex:
male/female
Type of coverage:
occlusive
Vehicle:
corn oil
Duration of exposure:
24 h
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 per sex per dose
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels:
No significant signs of systemic toxicity.
Gross pathology:
Effects on organs:
No treatment-related findings at examination post-mortem.
Other findings:
Signs of toxicity (local):
Slight or moderate erythema in three males and two females and small scattered scabs and desquamation in one female.
All signs of irritation had completely resolved by day 9.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the rat was found to be greater than 2000 mg/kg bodyweight.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
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 the 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 the 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

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

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

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