L-97-034-PB

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

3rd - 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

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

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
Five male and five female Sprague-Dawley CD (Crl: CD®BR) strain rats supplied by Charles River (UK) Ltd., Margate, Kent, were used. At the start of the main study the males weighed 212 to 227 g, and the females 206 to 216 g, and were approximately eight to twelve weeks old. After a minimum acclimatisation period of at 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 suspended polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-hour exposure period and in groups of five, by sex, for the remainder of the study. 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 18 to 22°C and relative humidity of 47 to 61%. On one occasion the temperature was below the limit specified in the protocol (19°C). This deviation was considered not to affect the purpose or integrity of the study. 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

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

On the day before treatment the back and flanks of each animal were clipped free of hair using veterinary clippers.

A single group of animals was treated as follows:

Dose Level Specific Gravity Dose Volume Number of Rats
(mg/kg) (ml/kg) Male Female
2000 0.958 2.09 5 5

The calculated volume of test material, as received, was applied uniformly to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self adhesive bandage. The bandage was further secured with a piece of BLENDERM wrapped around each end. The animals were caged individually for the 24-hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5 male and 5 female

Control animals:

not required

Details on study design:

After the 24-hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material. The animals were returned to group housing for the remainder of the study period.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the following scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.

Statistics:

No statistical analysis was performed.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred during the study.

Clinical signs:

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

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

None

Any other information on results incl. tables

Table 1: 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)
2000		1/2	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
	1 -0 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 -1 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 -2 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 -3 Male	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	1 -4 Male	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
	2 -3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	2 -4 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

Table 2: Individual dermal reactions

Dose Level (mg/kg)	Animal Number and Sex	Observation	Effects Noted After Initiation of Exposure (Days)
			1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	1 -0 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1 -1 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1 -2 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1 -3 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	1 -4 Male	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2 -0 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2 -1 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2 -2 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2 -3 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0
	2 -4 Female	Erythema Oedema Other	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0	0 0 0

Table 3: Individual bodyweights and weekly bodyweight changes

Dose Level (mg/kg)	Animal Number and Sex	Bodyweight (g) at Day			Bodyweight Gain (g) During Week
		0	7	14	1	2
2000	1 -0 Male 1 -1 Male 1 -2 Male 1 -3 Male 1 -4 Male 2 -0 Female 2 -1 Female 2 -2 Female 2 -3 Female 2 -4 Female	223 218 227 212 217 210 206 216 207 213	280 267 280 259 274 225 230 231 209 218	340 311 340 319 340 234 249 248 216 229	57 49 53 47 57 15 24 15 2 5	60 44 60 60 66 9 19 17 7 11

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was found to be greater than 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.

Executive summary:

Introduction

A study was performed to assess the acute dermal 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. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Method

A group of ten animals (five males and five females) was given a single 24 -hour, semi-occluded dermal application to intact skin at a dose level of 2000 mg/kg bodyweight. The animals were observed for fourteen days after the day of dosing and were then killed for 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 2000 mg/kg bodyweight. No symbol and risk phrase are required according to EU labelling regulations.