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Administrative data

Description of key information

GLP-studies according to OECD guidelines 404 and 405 are available for 2-butoxyethyl benzoate.

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:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was condcuted according to OECD TG 404, EPA TG OPPTS 870.2500 and in accordance with the Principles of Good Laboratory Practice (GLP).
Reason / purpose for cross-reference:
reference to same study
Reason / purpose for cross-reference:
reference to other study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: inhouse bred (outbred)
- Age at study initiation: 7-8 months
- Weight at study initiation: 2.71 - 2.91 kg
- Housing: individually housed in rabbit cages (approx. size: L 65 x B 65 xH 45 cm) under standard laboaratory conditions
- Diet (ad libitum): The animals were offered rabbit feed manufactured by Pranav Agro Industries Ltd, Sangli, Maharashtra, India.
- Water (ad libitum): The animals were provided deep bore-well water passed through activated charcoal
filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier. The water was replenished once daily and the water bottles changed once a week.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 23°C
- Humidity (%): 64-67%
- Air changes (per hr): 12-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hour light and 12 hour dark cycle
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): A volume of 0.5 mL of the undiluted test substance was applied on to the test site of approximately 6 cm2 (2 x 3 cm) and covered by a 6-ply gauze pad. The entire trunk of each animal was then wrapped with non-irritating semi-occlusive adhesive tape to avoid dislocation of the patch.
Duration of treatment / exposure:
4-hour exposure period
Observation period:
7 days
Number of animals:
3 rabbits
Details on study design:
TEST SITE
- Area of exposure: Approximately 24 hours before treatment, the fur on the left side of the dorsolateral trunk surface [about 14 x 19 cm] was clipped with an electric clipper -Aesculap®- Germany. Care was taken to avoid abrading the skin. After clipping and prior to application, the animal’s skin (test site) was checked for any abnormalities according to the “Primary Skin Irritation Scoring System”, and the test site was found to be normal.
- % coverage: An approximately 6 cm2 intact test site was selected on each animal. The adjacent untreated skin of each animal served as the control site.
- Type of wrap if used: A volume of 0.5 mL of the undiluted test substance was applied on to the test site of approximately 6 cm2 (2 x 3 cm) and covered by a 6-ply gauze pad. The entire trunk of each animal was then wrapped with non-irritating semi-occlusive adhesive tape to avoid dislocation of the patch.
- The rabbits were restrained using an Elizabethan collar for 4 hours during the contact period of test substance.

REMOVAL OF TEST SUBSTANCE
- Washing: Following the exposure period, test patches were removed and the test sites were washed with de-ionised water to remove any residual test substance.

SCORING SYSTEM: The test sites were examined for signs of erythema and edema within 60 minutes and at intervals of approximately 24, 48 and 72 hours and on Day 7 after test patch removal according to the "Primary Skin Irritation Scoring System" developed by Draize, et.al (1944).
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
mean
Remarks:
of all animals
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
of all animals
Time point:
other: 24, 48 and 72 hours
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 7 days
Irritant / corrosive response data:
Erythema score of 1 was observed in two rabbits (RB9663 & RB 9664) at 24, 48 and 72 hours post removal of the test patch. Erythema and Edema score of 1 was observed in the third rabbit (RB9665) at 24, 48 and 72 hours post removal of the test patch. The skin at the treated site of all the three rabbits was normal on the 7th day post removal of the test patch
Other effects:
There were no clinical signs of toxicity or mortality observed during the course of the study and the body weights of all the rabbits increased throughout the observation period.

None

Interpretation of results:
GHS criteria not met
Conclusions:
Under the testing conditions of this study, 2-butoxyethyl benzoate caused erythema (score of 1) in 3 rabbits and edema (score of 1) in one rabbit and these scores were completely reversed by day 7 post removal of the test patch and according to Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, 2-butoxyethyl benzoate will be not classified for skin irritation.
Executive summary:

The acute dermal irritation/corrosion study in rabbits was conducted to evaluate the skin irritation potential of 2-butoxyethyl benzoate. All the three rabbits were treated at the same time (4 hours only) as per sponsor’s request. A volume of 0.5 mL of the undiluted test substance was applied on to the test site of approximately 6 cm2 (2 x 3 cm) and covered by a 6-ply gauze pad. The patch was secured to the body of the animal by a non-irritating semi-occlusive adhesive tape. The patch was removed after 4 hours of skin contact. All test sites were evaluated for skin irritation according to the Draize (1944) evaluation method.

There were no clinical signs of toxicity or mortality observed during the course of the study and the body weights of all the rabbits increased throughout the observation period. Erythema score of 1 was observed in two rabbits (RB9663 & RB 9664) at 24, 48 and 72 hours post removal of the test patch. Erythema and Edema score of 1 was observed in the third rabbit (RB9665) at 24, 48 and 72 hours post removal of the test patch. The skin at the treated site of all the three rabbits was normal on the 7th day post removal of the test patch.

Under the testing conditions of this study, 2-butoxyethyl benzoate caused erythema (score of 1) in 3 rabbits and edema (score of 1) in one rabbit and these scores were completely reversed by day 7 post removal of the test patch and according to Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, 2-butoxyethyl benzoate will be not classified for skin irritation.

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:
2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose for cross-reference:
reference to same study
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
Principles of method if other than guideline:
not applicable
GLP compliance:
yes (incl. QA statement)
Specific details on test material used for the study:
Batch Manufactured and Supplied By: The Dow Chemical Company, Midland, MI, 48674, USA
Chemical Name : 2-Butoxy-ethanol benzoate
Physical Description (color + physical state): Variable coloured liquid
Purity : 99.86%
Lot No. : 02112012-JLT
pH : 6.08 (1% aqueous solution analyzed at Advinus under study no. G8567)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: inhouse bred (outbred)
- Age at study initiation: 7-8 months
- Weight at study initiation: 2.8 - 2.94 kg
- Housing: The rabbits were housed individually in rabbit cages (approx. size: L 65 x B 65 xH 45 cm) under standard laboratory conditions
- Diet (ad libitum): The animals were offered rabbit feed manufactured by Pranav Agro Industries Ltd, Sangli, Maharashtra, India.
- Water (ad libitum): The animals were provided deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier. The water was replenished once daily and the water bottles changed once a week.
- Acclimation period: 5-6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 22°C
- Humidity (%): 56-65%
- Air changes (per hr): 12-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle
Vehicle:
unchanged (no vehicle)
Controls:
yes, concurrent no treatment
Amount / concentration applied:
A volume of 0.1 mL of the undiluted test substance was instilled into the eye of the rabbits.
Duration of treatment / exposure:
A volume of 0.1 mL of the test substance was placed in the everted lower lid (conjunctival sac) of the left eye of each of three rabbits. The eye lids were gently held together for about one second, in order to minimize loss of the test substance.
Observation period (in vivo):
1, 24, 48 and 72 hours post instillation.
Number of animals or in vitro replicates:
3 male rabbits
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Time after start of exposure: A volume of 0.1 mL of the test substance was placed in the everted lower lid (conjunctival sac) of the left eye of each of three rabbits. The eye lids were gently held together for about one second, in order to minimize loss of the test substance. The right eye of each rabbit remained untreated and served as the reference control.

SCORING SYSTEM: The eyes were evaluated with the illumination of a white light source at intervals of approximately 1, 24, 48 and 72 hours post instillation of the test substance according to the "Scale for Scoring Ocular Lesions" (Draize, 1944).

TOOL USED TO ASSESS SCORE: The fluorescein dye evaluation procedure was used for the treated eyes at 24 hours post instillation of the test substance to verify the extent or absence of corneal damage.
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
RB9666
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
RB9666
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
RB9666
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
RB9666
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
RB9667
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
RB9667
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
RB9667
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
RB9667
Time point:
24/48/72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
RB9668
Time point:
24/48/72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
RB9668
Time point:
24/48/72 h
Score:
0
Irritation parameter:
conjunctivae score
Basis:
animal #3
Remarks:
RB9668
Time point:
24/48/72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
RB9668
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
Eye Reactions:
There was no eye irritation (iritis, conjunctival irritation or corneal opacity) observed in any treated eye during the study at 1, 24, 48 and 72 hours post instillation.
After the completion of the study the animals were released for euthanasia and humanely euthanized.
Other effects:
Clinical Observations:
There were no clinical signs of toxicity or mortality observed during the study.

Body Weights:
The body weights of all rabbits increased slightly throughout the observation period.

The individually determined mean irritation scores for each animal for corneal opacity, iris lesion, conjunctival redness and conjunctival chemosis for the 24-, 48- and 72-hour intervals are:

 

Animal No.

(Sex)

Corneal

Opacity

Iris Lesion

Conjunctival

Redness

Conjunctival

Chemosis

RB9666 (M)

0

0

0

0

RB9667 (M)

0

0

0

0

RB9668 (M)

0

0

0

0

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, 2-butoxyethyl benzoate did not cause any eye irritation.
Executive summary:

An acute eye irritation / corrosion study in rabbits was conducted to evaluate the eye irritation potential of 2-butoxyethyl benzoate. Under the conditions of this study, 2-butoxyethyl benzoate did not cause any eye irritation.

The test was performed in a stepwise manner. A single rabbit was initially exposed to the test substance. Since the test substance was not corrosive or severely irritating, the study was completed using two additional rabbits.

A quantity of 0.1 mL of the test substance was placed in the everted lower lid (conjunctival sac) of the left eye of each of three rabbits. The lids were gently held together for about one second, in order to minimize loss of the test substance. The right eye of each rabbit remained untreated and served as the reference control. The eyes were evaluated at 1, 24, 48 and 72 hours post instillation according to the scale for scoring ocular lesions (DRAIZE, 1944). There were no clinical signs of toxicity or mortality. All rabbits appeared healthy and gained body weight

throughout the observation period.

There was no eye irritation (iritis, conjunctival irritation or corneal opacity) observed in any treated eye during the study at 1, 24, 48 and 72 hours post instillation.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Skin Irritation Study:

The acute dermal irritation/corrosion study in rabbits was conducted to evaluate the skin irritation potential of 2-butoxyethyl benzoate. All the three rabbits were treated at the same time (4 hours only). A volume of 0.5 mL of the undiluted test substance was applied on to the test site of approximately 6 cm2 (2 x 3 cm) and covered by a 6-ply gauze pad.

There were no clinical signs of toxicity or mortality observed during the course of the study and the body weights of all the rabbits increased throughout the observation period. Erythema score of 1 was observed in two rabbits at 24, 48 and 72 hours post removal of the test patch. Erythema and Edema score of 1 was observed in the third rabbit at 24, 48 and 72 hours post removal of the test patch. The skin at the treated site of all the three rabbits was normal on the 7th day post removal of the test patch.

Under the testing conditions of this study, 2-butoxyethyl benzoate caused erythema (score of 1) in 3 rabbits and edema (score of 1) in one rabbit and these scores were completely reversed by day 7 post removal of the test patch and according to Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, 2-butoxyethyl benzoate will be not classified for skin irritation.

Eye Irritation Study:

An acute eye irritation / corrosion study in rabbits was conducted to evaluate the eye irritation potential of 2-butoxyethyl benzoate. The test was performed in a stepwise manner. A quantity of 0.1 mL of the test substance was placed in the everted lower lid (conjunctival sac) of the left eye of each of three rabbits. The lids were gently held together for about one second, in order to minimize loss of the test substance. The right eye of each rabbit remained untreated and served as the reference control. There were no clinical signs of toxicity or mortality. All rabbits appeared healthy and gained body weight throughout the observation period.

There was no eye irritation (iritis, conjunctival irritation or corneal opacity) observed in any treated eye during the study at 1, 24, 48 and 72 hours post instillation.

Justification for classification or non-classification

Skin Irritation Study:

Under the testing conditions of this study, 2-butoxyethyl benzoate caused erythema (score of 1) in 3 rabbits and edema (score of 1) in one rabbit and these scores were completely reversed by day 7 post removal of the test patch and according to Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, 2-butoxyethyl benzoate will be not classified for skin irritation.

Eye Irritation Study:

There was no eye irritation (iritis, conjunctival irritation or corneal opacity) observed in any treated eye during the study at 1, 24, 48 and 72 hours post instillation and according to Guidance to regulation (EC) No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, 2-butoxyethyl benzoate will be not classified for eye irritation.