tris(branched-alkyl) borate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 June 2014 to 16 July 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: There were no deviations (unplanned changes) from the study plan.

Cross-reference

Reason / purpose for cross-reference:

reference to other study

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 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test material form:

liquid

Details on test material:

- Appearance/physical state: Clear colourless liquid
- 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 s were suppiied by Harlan Laboratories UK Ltd., Oxon, UK.
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 animais were selected at random and given a number unique within the study by indelible inkmarking on the tail and a number written on a cage card.
At the start of the study the animais were eight to tweive 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 four in suspended solid-floor poiypropyiene cages furnished with woodflakes. With the exception of an overnight fast immediateiy before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food 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.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

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 dose level to confirm the survival of the previously dosed animals.

Doses:

2000 mg/kg

No. of animals per sex per dose:

4 (main study) + 1 (preliminary) for a total of 5

Control animals:

no

Details on study design:

A total of five animals were therefore treated at a dose level of 2000 mg/kg in the study.
Clinical observations were made 1/2, 1, 2, and 4 hours after dosing and then daily for fourteen days. Morbidity and mortality checks were made twice daily.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an extemal examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

No statistic: 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:

Yes, with one female

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths.

Clinical signs:

Hunched posture was noted two and four hours after dosing in the initial treated animal. No signs of systemic toxicity were noted in the additional treated animals during the observation period.

Body weight:

All animals showed expected gains in body weight over the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table1     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)
		Yz	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1-0 Female	0	0	H	H	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
	2-3 Female	0	0	0	0	0	0	0	0	0	0	0   ---	0	0	0	0	0	0	0

H = hunched posture

0 = No signs of systemic toxicity

Table 2     lndividual 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		167	181	191	14	10
	2-0 Female		171	182	200	11	18
	2-1 Female		175	202	218	27	16
	2-2 Female		175	195	210	20	15
	2-3 Female		173	193	206 --	20	13   1

Table3     lndividual Necropsy Findings

Dose Level mg/kg	Animal Numbe rand Sex	Time of Death	Macroscopic Observations
2000	1-0 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
	2-3 Female	Killed Day 14	No abnormalities detected

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 considered to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System - Unclassified).

Executive summary:

Introduction

The study was performed to OECD Guideline No. 420 and EU Method B.1 bis to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

Following a sighting test at a dose level of 2000 mg/kg, an additional four fasted female animals were given a single oral dose of test item at a dose level of 2000 mg/kg body weight. 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 during the day of dosing in the initial treated animal. There were no signs of systemic toxicity noted in the additional treated 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 considered to be greater than 2000 mg/kg body weight (Globally Harmonized Classification System- Unclassified).