L-97-034-PB

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26th January - 17th February 1998

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1998

Report date:

1998

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Pentaerythritol mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Cas Number:

141686-49-9

IUPAC Name:

Pentaerythritol mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Constituent 2

Reference substance name:

Trimethylol propane mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Cas Number:

141686-50-2

IUPAC Name:

Trimethylol propane mixed esters with 2-methyl butyric acid, n-pentanoic acid, n-heptanoic acid, 3,5,5-trimethylhexanoic acid, n-octanoic acid, n-decanoic acid

Test material form:

liquid

Details on test material:

Identification: Hatcol ® 1772
Appearance/physical state: Clear colorless liquid
Purity: 100% (no solvent present)
Composition: 70% pentaerythritol esters described by CAS# 141686-49-9; 30% trimethylolpropane esters described by CAS# 141686-50-2

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

ANIMAL INFORMATION
Male and female Sprague-Dawley CD (Crl: CD®BR) strain rats supplied by Charles River (UK) Ltd., Margate, Kent, UK. were used. At the start of the main study the males weighed 210 to 225 g, and the females 201 to 218 g, and were eight to twelve weeks of age. After an acclimatisation 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.

ANIMAL CARE AND HUSBANDRY
The animals were housed in groups of up to five by sex in 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 (Rat and Mouse Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout the study.

The animal room was maintained at a temperature of 19 to 21°C and relative humidity of 50 to 67%. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

One dose of test material (5000 mg/kg)

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the study.

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual clinical observations and mortality data in the range-finding study

Dose level (mg/kg)	Animal Number and Sex	Effects noted after dosing (hours)				Effects noted during period after dosing (hours)
		0.5	1	2	4	1	2	3	4
5000	1 -0 Male	0	0	0	0	0	0	0	0
	2 -0 Female	0	0	0	0	0	0	0	0

Table 2: Individual bodyweights and weekly bodyweight changes in the main study

Dose level (mg/kg)	Animal Number and Sex	Bodyweight (g) at day			Bodyweight gain (g) during week
		0	7	14	1	2
5000	3 -0 Male	216	297	352	81	55
	3 -1 Male	225	320	388	95	68
	3 -2 Male	222	299	351	77	52
	3 -3 Male	221	302	375	81	73
	3 -4 Male	210	284	330	74	46
	4 -0 Female	218	270	296	52	26
	4 -1 Female	201	238	250	37	12
	4 -2 Female	209	246	258	37	12
	4 -3 Female	205	240	257	35	17
	4 -4 Female	211	257	268	46	11

Table 3: Individual necropsy findings in the main study

Dose level (mg/kg)	Animal Number and Sex	Time of Death	Macroscopic Observations
5000	3 -0 Male	Killed Day 14	No abnormalities detected
	3 -1 Male	Killed Day 14	No abnormalities detected
	3 -2 Male	Killed Day 14	No abnormalities detected
	3 -3 Male	Killed Day 14	No abnormalities detected
	3 -4 Male	Killed Day 14	No abnormalities detected
	4 -0 Female	Killed Day 14	No abnormalities detected
	4 -1 Female	Killed Day 14	No abnormalities detected
	4 -2 Female	Killed Day 14	No abnormalities detected
	4 -3 Female	Killed Day 14	No abnormalities detected
	4 -4 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 material, in the Sprague-Dawley CD strain rat was found to be greater than 5000 mg/kg bodyweight.

Executive summary:

Introduction

A study was performed to assess the acute oral toxicity of the test material in the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 401 "Acute Oral Toxicity" (adopted February 1987) and Method B1 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC) and the US EPA Health Effects Test Guidelines OPPTS 870.1100 (draft).

Method

Following a range-finding study, a group of ten fasted animals (five males and five females) was given a single dose of undiluted test material, at a dose level of 5000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed and subjected to gross pathological examination.

Mortality

There were no deaths.

Clinical signs

No signs of systemic toxicity were noted during the study.

Body weight

All animals showed an expected gain in bodyweight during the study.

Gross pathology

No abnormalities were noted at necropsy.

Conclusion

The acute oral median lethal dose (LD50) of the test material, in the Sprague-Dawley CD strain rat was found to be greater than 5000 mg/kg bodyweight.

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