Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 Oct 2016 - 02 Feb 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
The study was conducted in accordance with international guidelines and in accordance with GLP. All relevant validity criteria were met.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2017
Report Date:
2017

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Used for data analysis where dosing performed in the study is below 5000 mg/kg
Deviations:
yes
Remarks:
The pre-test body weight of Animal 4 exceeded + 20% of the mean pre-test body weights of the previously dosed animals. No impact on the study.
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
yes
Remarks:
The pre-test body weight of Animal 4 exceeded + 20% of the mean pre-test body weights of the previously dosed animals. No impact on the study.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
The pre-test body weight of Animal 4 exceeded + 20% of the mean pre-test body weights of the previously dosed animals. No impact on the study.
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
Details on test material:
Storage Conditions:Stable at ambient temperature (10-30°C). Store in darkness; may be used/formulated in light.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River, Raleigh NC and Stone Ridge NY
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: body weight variation did not exceed ±20% of the mean body weight at the start of treatment
- Fasting period before study: yes
- Housing: Animals were individually housed in suspended wire-bottom cages that conform to the size recommendations in the Guide for the Care and Use of Laboratory Animals (National Research Council). Absorbent paper bedding, placed beneath the cage, changed at least three times per week.
- Diet (e.g. ad libitum): Fresh PMI Rat Chow (Diet #5012) will be available ad libitum except for 16 to 20 hours prior to dosing.
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): Exact temperature was not indicated but both temperature and humidity was continuously recorded using automated recording device.
- Humidity (%): Exact temperature was not indicated but both temperature and humidity was continuously recorded using automated recording device.
- Air changes (per hr): Not reported
- Photoperiod (hrs dark / hrs light): 12 : 12
IN-LIFE DATES: Not clarified in the study report

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
The test article was administered orally by syringe and a dosing needle on an mg/kg basis.
Initially, a single female Sprague Dawley rat was dosed orally with TX16352 at a dose level of 2000 mg/kg. Since the animal survived, four additional females were dosed at 2000 mg/kg.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Each animal was given single dose of 2.0 mL - 2.5 mL dose volume of 2000 mg/kg of the test item (i.e. animal 1&2: 20.mL, animal 3&5 : 2.2 mL and animal 4 received 2.5 mL)
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 0.25, 1, 2 and 4 hours after dosing then daily thereafter for 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and body weight
Statistics:
not required

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:
No deaths reported
Clinical signs:
Piloerection, partially chewed food, chromorhinorrhea, few feces, and localized hair loss (side of neck) were observed.
Body weight:
all animals showed expected weight gain.
Gross pathology:
No abnormalities noted at necropsy.

Any other information on results incl. tables

Table 1:   Number of animals dead (and with evident toxicity)

 

Dose

(mg/kg bw

 

 

Mortality

(# dead / total)

 

Time range of deaths

(hours)

 

 

Number with evident toxicity

(# / total)

 

Male

Female

Combined

Male

Female

Combined

 

-

0/5

0/5

n/a

-

0/5

0/5

Table 2. Systemic Observation

Dose

2000 mg/kg

Animal ID/sex

1F

2F

3F

4F

5F

Time period

 

 

 

 

 

15 minutes

 

S

 

 

 

Hour 1

 

F,S

 

F

 

Hour 2

 

R

 

F

F

Hour 4

 

F

1

 

 

Day 1

F

F,S,X

1

 

 

Day 2

 

F,S,X

1

 

 

Day 3

 

 

1

 

 

Day 4

 

 

1

 

 

Day 5

 

 

 

2

 

Day 6

 

 

 

2

 

Day 7

 

 

 

 

 

Day 8

 

 

 

 

 

Day 9

 

 

 

 

 

Day 10

2

 

 

 

 

Day 11

 

 

 

 

 

Day 12

 

 

 

 

 

Day 13

2

 

 

 

 

Day 14

 

 

 

 

 

No entry indicates animal appeared normal at that observation period.
1 = Hair loss: left side of the neck 2 = Partially chewed food on pan liner F = Piloerection S = Chromorhinorrhea X = Few feces

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System Unclassified).
Executive summary:

OECD 425 (2017) - In an acute oral toxicity study, a group of fasted, 8-12 week old female Wistar rats were given a single oral dose of TX16352 at a single dose rate of 2000 mg/kg bw (limit test) and observed for 14 days.

In the absence of mortality during the observation period, the oral LD50 was estimated to be greater than 2000 mg/kg bw.

In addition, there were no treatment related clinical signs, necropsy findings or changes in body weight observed in any of the individuals.

In conclusion, the test item, TX16352 did not meet the criteria for classification according to Regulation (EC) No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixture.