Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 Sept 2017 to 23 Jan 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018
Report Date:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
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 (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
White powder

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Test Animals
Animals were received from Charles River, Raleigh NC and Stone Ridge, NY on 12 Sep 2017, 26 Sep 2017, 03 Oct 2017, and 26 Oct 2017. Following an acclimation period of at least five days, seven healthy, non-pregnant, nulliparous female Sprague Dawley rats were selected for dosing without conscious bias.
The animals were born on 17 Jul 2017, 31 Jul 2017, and/or 30 Aug 2017. The pre-test body weight range was 206 - 224 grams. The weight variation of the animals used did not exceed ± 20% of the mean weight of the previously dosed animals.
The animals were identified by cage notation and indelible tail marks corresponding to the numbers entered on the data collection forms. The animals were individually housed in suspended wire-bottom cages. Absorbent paper bedding was placed beneath the cages and changed at least three times per week. Fresh PMI Rat Chow (Diet No.5012) was available ad libitum 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:
Dosing
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. Initially, a single female Sprague Dawley rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal died, additional animals were dosed, one at a time, by a single ordered dose progression.
Doses:
2000mg/kg, 550mg/kg
No. of animals per sex per dose:
1 per dose
Control animals:
no
Details on study design:
Type and Frequency of Observations
In Vivo - Animals were observed at 15 minutes, 1, 2 and 4 hours post-dosing and once daily thereafter for
14 days for toxicity and pharmacological effects. Observations included, but were not limited to, evaluation
of skin and fur, eyes and mucous membranes, respiratory and circulatory effects, autonomic effects such as
salivation, central nervous system effects including tremors and convulsions, changes in the level of activity,
gait and posture, reactivity to handling or sensory stimuli, altered strength, and stereotypies or bizarre
behavior (e.g., self-mutilation, walking backwards). All animals were observed twice daily for mortality on
Day 1 to Day 14. Body weights were recorded pre-test, weekly, and at death or termination in the survivors.
Post Mortem – All animals were humanely euthanized using CO2 following study termination and
examined for gross pathology.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
2 000 mg/kg bw
Based on:
test mat.
95% CL:
0 - 20 000
Mortality:
2000 mg/kg; Three female rats survived following a single oral dose of 2000 mg/kg. Two female rats died, by Day 3, following a single oral dose of 2000 mg/kg.
550 mg/kg: Two female rats survived following a single oral dose of 550 mg/kg.
Clinical signs:
2000 mg/kg; Prior to death, abnormal physical signs including diarrhea, soiling and wetness of the anogenital area, few feces, piloerection, wetness of the nose/mouth area and abdomen, ataxia, partially chewed food, and chromorhinorrhea were observed. Among the surviving animals, piloerection, chromodacryorrhea, few feces, wetness and yellow staining of the anogenital area, wetness, yellow staining and thinning hair on the abdomen, lethargy, and emaciation were observed.
550 mg/kg: Wetness of the anogenital area was observed in one animal two to four hours following dose administration. No other abnormal physical signs were observed.
Body weight:
2000 mg/kg; Body weight loss was observed among the animals that died. The three surviving animals gained body weight by study termination.
550 mg/kg: Both animals gained body weight by study termination.
Gross pathology:
2000 mg/kg; The gross necropsy of the animals that died revealed chromodacryorrhea, wetness of the nose/mouth area, wetness and yellow staining of the anogenital area, wetness on the abdomen and abnormalities of the gastrointestinal tract. Of the surviving animals, thinning hair on the abdomen was observed on one animal and no abnormalities were observed among two animals.
550 mg/kg: The gross necropsy revealed no observable abnormalities.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The estimated oral LD50 and 95% confidence limits of L-006266209-000K003 is 2000 (0 to 20,000) mg/kg of body weight in female rats.
DOT: Not poisonous, no packing group required
EPA: Category III
GHS: Category 5