α-phenyl-1H-benzimidazole-2-methanol

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

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.

Test guideline 2

Qualifier:

according to guideline

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.

Test guideline 3

Qualifier:

according to guideline

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. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

α-phenyl-1H-benzimidazole-2-methanol

EC Number:

200-073-0

EC Name:

α-phenyl-1H-benzimidazole-2-methanol

Cas Number:

50-97-5

Molecular formula:

C14H12N2O

IUPAC Name:

α-phenyl-1H-benzimidazole-2-methanol

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 or test system 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:

other: Piloerection, partially chewed food, chromorhinorrhea, few feces, and localized hair loss (side of neck) were observed.

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.