Reaction mass of bis(2-ethylhexyl) terephthalate, butyl 2-ethylhexyl terephthalate, and dibutyl terephthalate

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

This study was conducted between 09 July 2013 and 26 July 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

EC No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction mass of bis(2-ethylhexyl) terephthalate, butyl 2-ethylhexyl terephthalate, and dibutyl terephthalate

EC Number:

946-149-3

Cas Number:

1571954-81-8

IUPAC Name:

Reaction mass of bis(2-ethylhexyl) terephthalate, butyl 2-ethylhexyl terephthalate, and dibutyl terephthalate

Test material form:

liquid

Details on test material:

Identification: GL500
Test item (alternative names): LGflex GL500
GL500
GL520
CAS No: 1571954-81-8
Action of test item: Plasticizer
Appearance/Physical state: Clear colorless liquid
Batch: GLFG160607
Purity: 99.8%
Expiry date: 07 June 2017
Storage conditions: Room temperature in the dark

Specific details on test material used for the study:

Batch: 20130510
Purity: 99.81%
Expiry date: 10 May 2018
Storage Conditions: room temperature in the dark

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

Hsdlf:NZW

Details on test animals or test system and environmental conditions:

Three New Zealand White (Hsdlf:NZW) strain rabbits were supplied by Harlan Laboratories UK Ltd., Leicestershire, UK. At the start of the study the animals weighed 2.24 to 3.04 kg and were twelve to twenty weeks old. After an acclimatization period of at least five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended cages. Free access to mains drinking water and food (2930C Teklad Global Rabbit diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet and drinking water were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 17 to 23 oc and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. 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.

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Test material:
Used as supplied
- Applied volume: 0.5 mL
- Concentration (if solution): undiluted

Duration of treatment / exposure:

3 minutes, 1 hour and 4 Hours

Observation period:

1, 24, 48 and 72 hours

Number of animals:

3

Details on study design:

Study Design
On the day before the test each of a group of three rabbits was clipped free of fur from the dorsal/flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
On the day of the test a suitable test site was selected on the back of each rabbit. A quantity of 0.5 mL of the test item was applied directly to the skin under a 2.5 cm x 2.5 cm cotton gauze patch. The patch was secured in position with a strip of surgical adhesive tape. To prevent the animals interfering with the patches, the trunk of each rabbit was wrapped in an elasticated corset and the animals were returned to their cages for the duration of the exposure period.
Four hours after application the corset and patches were removed from each animal and any residual test item removed by gentle swabbing with cotton wool soaked in 74% industrial methylated spirit.
Immediately following removal of the patches and approximately 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the following scale:

EVALUATION OF SKIN REACTIONS
Erythema and Eschar Formation Value
No erythema 0
Very slight erythema (barely perceptible) 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema (beef redness) to eschar formation
preventing grading of erythema 4

Edema Formation
No edema 0
Very slight edema (barely perceptible) 1
Slight edema (edges of area well-defined by definite raising) 2
Moderate edema (raised approximately 1 millimeter) 3
Severe edema (raised more than 1 millimeter and
extending beyond the area of exposure) 4

Any other skin reactions and clinical signs of toxicity, if present, were also recorded.
Additional observations were made on Days 7 and 14 to assess the reversibility of skin reactions.
Individual body weights were recorded on Day 0 (the day of dosing) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test item produced a primary irritation index of 0.0 and was classified as non- irritant to rabbit skin according to the Draize classification scheme.

Other effects:

Skin Reactions
3-Minute Exposure Period
No evidence of skin irritation was noted during the study (Table 1).

I-Hour Exposure Period
No evidence of skin irritation was noted during the study.

4-Hour Exposure Period
No evidence of skin irritation was noted during the study.

Body Weight
All animals showed expected gain in body weight during the study

Any other information on results incl. tables

Skin Reactions

3-Minute Exposure Period

No evidence of skin irritation was noted during the study (Table 1).

I-Hour Exposure Period

No evidence of skin irritation was noted during the study (Table 1).

4-Hour Exposure Period

No evidence of skin irritation was noted during the study (Table 2).

Body Weight

All animals showed expected gain in body weight during the study

Table 1: Individual Skin Reactions Following 3-Minute and 1-Hour Exposure

Skin Reaction	Observation Time (following patch removal)	Individual Score Rabbit 73321 Male
		3 -Minute exposure	1 -Hour exposure
Erythema/Eschar Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0
Edema Formation	Immediately	0	0
	1 Hour	0	0
	24 Hours	0	0
	48 Hours	0	0
	72 Hours	0	0

Table 2     Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction	Observation Time (following patch removal)	Individual Scores			Total
		Rabbit Number and Sex
		73321Male	73376Male	73375Male
Erythema/Eschar Formation	Immediately	0	0	0	(0 )
	1 Hour	0	0	0	( 0 )
	24 Hours	0	0	0	0
	48 Hours	0	0	0	( 0 )
	72 Hours	0	0	0	0
Edema Formation	Immediately	0	0	0	( 0 )
	1 Hour	0	0	0	( 0 )
	24 Hours	0	0	0	0
	48 Hours	0	0	0	( 0 )
	72 Hours	0	0	0	0
Sum of 24 and 72‑Hour Readings (S):          0
Primary Irritation Index (S/6)            :          0/6 = 0.0
Classification                                     :          NON‑IRRITANT

(   ) =   Total values not used for calculation of primary irritation index

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted

Executive summary:

The study was performed to assess the irritancy potential of the test item following single, 3-Minute, 1 and 4-Hour, semi-occluded applications to the intact rabbit skin.

Results

3-Minute and 1-Hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation.

Conclusion

The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme.  No corrosive effects were noted