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

Endpoint summary

Description of key information

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

The test item produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24 April 2002

Deviations:

no

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)

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

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.

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.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

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

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

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

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

06 August 2013 - 15 August 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Leicestershire, UK.
- Age at study initiation: Twelve to twenty weeks old.
- Weight at study initiation: 2.48 to 3.37 kg
- Housing: The animals were individually housed in suspended cages.
- Diet (e.g. ad libitum):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.
- Acclimation period: Five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour .
- Photoperiod (hrs dark / hrs light):The lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1mL

Duration of treatment / exposure:

8 hours

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment, according to the numerical evaluation (Draize, J.H, 1977)

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not specified
- Time after start of exposure: 8 hours

SCORING SYSTEM: Kay and Calandra system

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1h

Score:

2

Reversibility:

fully reversible within: 48h

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 48 Hours

Remarks on result:

positive indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 48/72h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

positive indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 48/72h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Reversibility:

fully reversible

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation noted at the 24-Hour observation.
All treated eyes appeared normal at the 48-Hour observation.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.
The test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

Introduction

The study was performed to assess the irritancy potential of the test item to the eye of the New Zealand White rabbit

Results

A single application of the test item to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. All treated eyes appeared normal at the 48-Hour observation.

Conclusion

The test item produced a maximum group mean score of 8.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

he test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Eye irritation: The test item produced a limited amount of irritation observed 1 hour after exposure, the mean irrititaion scores for conjuctival redness and chemosis were below the threshold for classification when considered as the mean value for measurements taken at 24,48 and 72 hours therfore the substance does not meet the criteria for Eye irritation according to Regulation (EC) No.1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Skin irritation: 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. According to the CLP criteria the substance is not classified for skin irritation as no adverse effects were observed.