Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17-06-2014 to 30-09-2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
lot L--005457795-001 G001

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Animals were received from Charles River, Raleigh NC and Portage Ml, on 10 Jun 2014 and 24 Jun 2014. Following an acclimation period of at least five days, six healthy, non-pregnant and nulliparous female Sprague Dawley rats were assigned to treatment groups without conscious bias.
The animals were born the on 13 Apr 2014 and 28 Apr 2014. The pretest body weight range was
185 - 212 grams. The weiqht variation of the animals used did not exceed +20% of the mean body weight of the previously dosed animals
The animals were identified by cage notation and indelible body marks, and housed in suspended wire cages; five per sex per cage prior to dosing and three per sex per cage following dosing. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat Chow (Diet #5012) was freely available except for 16-20 hours prior to dosing. Water was available ad libitum. The animal room, reserved exclusively for rats on acute tests, was temperature controlled, had a 12-hour light/dark cycle, and was kept clean and vermin free

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 2.003-2.004 g /10 ml
- Amount of vehicle (if gavage): 10 ml
- Justification for choice of vehicle: The test article was mixed with corn oil to make dosing by gavage possible. The dose was based on the dry weight of the test article.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
two groups of 3 females
Control animals:
no
Details on study design:
A single dose was administered orally by syringe and dosing needle at a dose level of 2000 mg/kg to six female rats.

Type and Frequency of Observations

In Vivo - Animals were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects and twice daily for mortality. Body weights were recorded immediately pretest, weekly and at termination.

Post Mortem - All animals were humanely sacrificed using C02 and were examined for gross pathology following study termination.

Analysis of Data -The test article was assigned to a toxic category and an estimate of the LD50 was made based on the mortality results.

The test article was assigned to a toxic category according to the current Globally Harmonized System of
Classification and Label-ing of Chemicals (GHS). United Nations - New York and Geneva.

Results and discussion

Effect levels
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 six female rats survived the 2000 mg/kg oral dose.
Clinical signs:
Localized hair loss on the face and right hip areas were observed.
Body weight:
All animals gained body weight by study termination.

Gross pathology:
The gross necropsy of four out of six animals revealed no observable abnormalities. Localized hair loss of the face/head and hip areas were observed between two animals.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
L-005457795-001 G001 is considered to be in Acute Toxic Category 5, or unclassified. The oral LD50 is greater than 2000 mg/kg of body weight in female rats.

Executive summary:

Objective: To determine the potential for oral toxicity using the Acute Toxic Class Determination. This study was designed to comply with the standards set forth in the current OECD Guidelines for the Testing of Chemicals, Guideline 423.  Guideline 423 is referred to in OPPTS870.1000 as an acceptable method to assess  lethality within a dose range.  The test article was assigned to a toxic category based on the mortality results and significant clinical signs of toxicity upto the Category 4 value tested according to the current Globally Harmonized System of Classification and Labeling of Chemicals (GHS).

 

 

Method Synopsis: Three healthy female Sprague Dawley rats were dosed orally with L-005026412-000K002 at 2000mg/kg.  An additional three healthy females were dosed as a confirmatory group at 2000mg/kg. The rats were observed at 15minutes, 1, 2 and 4 hours post dose and once daily for 14 days for toxicity and pharmacological effects and twice daily for mortality. Bodyweights were recorded immediately pretest , weekly and at termination .  All animals were examined for gross pathology. The test article was assigned to a toxic category based on the mortality response noted.

 

                        All six female rats survived the 2000 mg/kg oral dose.

Localized hair loss on the face and right hip areas were observed.

All animals gained body weight by study termination.

The gross necropsy of four out of six animals revealed no observable abnormalities.  Localized hair loss of the face/head and hip areas were observed between two animals.