[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Experimental Starting Date: 19 November 2013 Experimental Completion Date: 12 December 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

Identification: FAT 65088/A TE
Description: light yellow powder
Batch: CUF 176, 3011 SCE 346
Purity: 93.8% w/w
Expiry date: 29 September 2017
Storage Conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Female Wistar (RccHan™:WIST) strain rats were supplied by a reputable supplier . On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least five days the animals were selected at random and given a number unique within the study by indelible ink marking on the tail and a number written on a cage card. At the start of the study the animals were eight to twelve weeks of age. The body weight variation did not exceed ±20% of the body weight of the initially dosed animal.

The animals were housed in groups of up to three in suspended solid floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by a reputable supplier was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that would reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.


Justification for choice of species
Rats are the preferred species of choice as historically used for safety evaluation studies and are specified in the appropriate test guidelines.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

Test Item Formulation and Experimental Preparation
For the purpose of the study the test item was freshly prepared, as required, as a solution in dimethyl sulphoxide. Dimethyl sulphoxide was used because the test item did not dissolve/suspend in distilled water or arachis oil BP.

The test item was formulated within two hours of being applied to the test system. It is assumed that the formulation was stable for this duration.

No analysis was conducted to determine the homogeneity, concentration or stability of the test item formulation. This is an exception with regard to GLP and has been reflected in the GLP compliance statement.

Doses:

Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.

No. of animals per sex per dose:

Groups of fasted animals were treated as follows
Dose Level (mg/kg)
2000
2000
Concentration (mg/mL)
200
200
Dose Volume (mL/kg)
10
10
Number of Rats Female
3
3

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each group to confirm the survival of the previously dosed animals.

Control animals:

no

Details on study design:

The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.

Individual body weights were recorded prior to dosing and seven and fourteen days after treatment.

At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

Evaluation of Data
Data evaluations included the relationship, if any, between the exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioral and clinical observations, gross lesions, body weight changes, mortality and any other toxicological effects.

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:

A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg body weight. No signs of systemic toxicity were noted exsept two animals with hunched posture.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 95 5 CL not reported

Mortality:

There were no deaths.

Clinical signs:

other: Hunched posture was noted in two animals during the day of dosing. No signs of systemic toxicity were noted in four animals during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Individual Clinical Observations and Mortality Data

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Female	0	0	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-1 Female	0	H	H	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-1 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0=   No signs of systemic toxicity

H =  Hunched posture

Individual Body Weights and Body Weight Changes

Dose Level mg/kg	Animal Number and Sex	Body Weight (g) at Day			Body Weight Gain (g) During Week
		0	7	14	1	2
2000	1-0 Female	169	183	194	14	11
	1-1 Female	170	189	204	19	15
	1-2 Female	167	190	203	23	13
	2-0 Female	160	184	197	24	13
	2-1 Female	157	176	191	19	15
	2-2 Female	159	175	186	16	11

Individual Necropsy Findings

Dose Level mg/kg	Animal Number and Sex	Time of Death	Macroscopic Observations
2000	1-0 Female	Killed Day 14	No abnormalities detected
	1-1 Female	Killed Day 14	No abnormalities detected
	1-2 Female	Killed Day 14	No abnormalities detected
	2-0 Female	Killed Day 14	No abnormalities detected
	2-1 Female	Killed Day 14	No abnormalities detected
	2-2 Female	Killed Day 14	No abnormalities detected

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: Globally Harmonized Classification System

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:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

  

Methods

A group of three fasted females was treated with the test item at a dose level of 2000 mg/kg body weight. This was followed by a further group of three fasted females at the same dose level. Dosing was performed sequentially.

 

The test item was administered orally as a solution in dimethyl sulphoxide. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

  

Results

Mortality. 

There were no deaths.

 

Clinical Observations. 

Hunched posture was noted in two animals during the day of dosing. There were no signs of systemic toxicity noted in four animals.

 

Body Weight. 

All animals showed expected gains in body weight.

 

Necropsy. 

No abnormalities were noted at necropsy.

  

Conclusion

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).