Bis(2-(2-butoxyethoxy)ethyl) adipate

Endpoint summary

Description of key information

skin irritation (similar to OECD 404): not irritating
eye irritation (EPA OTS 798.4500): not irritating

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:

4 Nov 1997 - 11 Nov 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted generally according to an accepted and published method. Experimental documentation was limited but adequate for the purposes of this summary.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4470 (Acute Dermal Irritation)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Remarks:

lack of details on test substance

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Davidson Mill Breeding Laboratories, Jamesburg, New Jersey, USA- Age at arrival: 3 months- Fasting period before study: none- Housing: stainless steel cages- Diet: Lab Diet Certified Rabbit Diet #5322, ad libitum- Water: ad libitum- Acclimation period: 13 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18 - 24 (65 - 75 °F)- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: To: 4 Nov 1997 to 11 Nov 1997

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: not required, untreated sites of the same animal served as control

Amount / concentration applied:

0.5 mL

Duration of treatment / exposure:

4 hours

Observation period:

7 days Reading time points: 4.5, 24, 48, and 72 h and 7 days after treatment)

Number of animals:

6 (3 males, 3 females)

Details on study design:

TEST SITE- Area of exposure: approximately 6 cm²- Type of wrap if used: The area was covered with a 2.5 cm² surgical gauze pad (Johnson & Johnson). This was held in place with 3 inch Johnson & Johnson hypo-allergenic cloth tape, semi-occlusively. Animals were collared for the deration of the exposure to preclude access to the siteREMOVAL OF TEST SUBSTANCE- Washing (if done): Remaining test article was gently washed from the skin with water and paper towels.- Time after start of exposure: 4 hSCORING SYSTEM: Each site was then individually examined and scored at 30 and 60 minutes following unwrapping for erythema and edema according to the Draize Scoring System.OTHERThe hair of the mid-dorsal area of the trunk of each animal, between scapulae and pelvis, was shaved using an Oster small animal clipper with surgical head (#40). Care was taken to avoid abrasion of the skin during clipping. Prior to dose application, animals were placed into wooden restrainers.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0.72

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: One animal showed accumulation of loose fragments of horny layer of skin (stratum corneum). Peeling. Only uppermost layer involved.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

fully reversible within: 72 h

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: revrsibility: not applicable

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Other effects:

The animals did not exhibit any abnormal clinical signs for the duration of the study.

Table 1: Primary dermal irritation in rabbits / individual results

Rabbit (number)	4 ½ hr		24 hr		48 hr		72 hr		Day 7
	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema	Erythema	Edema
1	1	0	1	0	1	0	0	0	-	-
2	1	0	1	0	1	0	1	0	0	0
3	1	0	1	0	1	0	0	0	-	-
4	1	0	1	0	1	0	1	0	0	0
5	1	0	1	0	1	0	1	0	0	0*
6	1	0	0	0	0	0	0	0	-	-

* Accumulation of loose fragments of horny layer of skin (stratum corneum). Peeling. Only uppermost layer involved.

The primary dermal irritation index was 0.65. The animals in this study did not exhibit any abnormal signs for the duration of the study. Under the conditions of this study, the test article elicited minimal irritation.

 

 

 

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

CLP: not classifiedDSD: not classified

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:

27 Oct 1997 - 30 Oct 1997

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study was conducted generally according to an accepted and published method. Experimental documentation was limited but adequate for the purposes of this summary.

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS- Source: Davidson Mill Breeding Laboratories, Jamesburg, New Jersey, USA- Ag at arrival: 3 months- Fasting period before study: none- Housing: stainless steel cages- Diet: Lab Diet Certified Rabbit Diet #5322, ad libitum- Water: ad libitum- Acclimation period: 5 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18 - 24 (65 - 75 °F)- Photoperiod (hrs dark / hrs light): 12/12IN-LIFE DATES: From: To: 27 Oct 1997 - 30 Oct 1997

Vehicle:

unchanged (no vehicle)

Controls:

other: the other eye remained untreated and served as control

Amount / concentration applied:

0.1 mL

Duration of treatment / exposure:

Single administration without washing

Observation period (in vivo):

72 hoursReading time points: 1, 24, 48, and 72 h after treatment

Number of animals or in vitro replicates:

6 (3 male, 3 female)

Details on study design:

SCORING SYSTEM: Draize Scoring SystemTOOL USED TO ASSESS SCORE: fluorescein, hand-held ophthalmoscope

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

over all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

iris score

Basis:

mean

Remarks:

over all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: reversibility: not applicable

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

over all 6 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

over all 6 animals

Time point:

other: mean over 24, 48, and 72 hours

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 h

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: reversibility: not applicable

Table 1: Primary ocular irritiation in rabbits - Summary

Rabbit number	Bodyweight [kg]	Reading time [h]	Cornea		Iris	Conjunctivae
			Score	Area		Redness	Chemosis	Discharge
1	Init: 1.96	1	0	0	0	1	1	1
	-	24	0	0	0	1	0	0
	-	48	0	0	0	0	0	0
	Term: 1.86	72	0	0	0	0	0	0
2	Init: 1.97	1	0	0	0	1	1	1
	-	24	0	0	0	1	0	0
	-	48	0	0	0	0	0	0
	Term: 1.87	72	0	0	0	0	0	0
3	Init: 1.86	1	0	0	0	1	1	1
	-	24	0	0	0	1	0	0
	-	48	0	0	0	0	0	0
	Term: 1.76	72	0	0	0	0	0	0
4	Init: 1.99	1	0	0	0	1	0	1
	-	24	0	0	0	1	0	0
	-	48	0	0	0	0	0	0
	Term: 1.89	72	0	0	0	0	0	0
5	Init: 1.88	1	0	0	0	1	1	1
	-	24	0	0	0	0	0	0
	-	48	0	0	0	0	0	0
	Term: 1.79	72	0	0	0	0	0	0
6	Init: 2.0	1	0	0	0	1	1	1
	-	24	0	0	0	0	0	0
	-	48	0	0	0	0	0	0
	Term: 1.96	72	0	0	0	0	0	0

Interpretation of results:

not irritating

Remarks:

Migrated informationCriteria used for interpretation of results: EU

Conclusions:

CLP: not classifiedDSD: not classified

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion:

The available key study was conducted similar to the OECD 404 test guideline and in compliance with GLP (Nitka, 1997). Three New Zealand White rabbits received the neat test item at a volume of 0.5 mL on the shaved skin under semiocclusive conditions. After 4 h, the test item was removed by washing of the application sites and the animals were observed and scored for erythema and oedema for up to 7 days. According to the Draize Scoring System the mean erythema score over 24, 48 and 72 h out of all six animals was 0.72, the respective oedema score was 0. The erythema observed was fully reversible within 7 days. One animal showed accumulation of loose fragments of horny layer of skin (stratum corneum), however, only the uppermost layer was involved. The animals in this study did not exhibit any abnormal signs for the duration of the study. In conclusion, the test item was not irritating to the skin under the conditions of the test.

Eye irritation:

The available key study was conducted according to the EPA OTS 798.4500 (Acute Eye Irritation) test guideline and in compliance with GLP (Nitka, 1997). Three New Zealand White rabbits received the neat test item as a single instillation of 0.1 mL into one eye, whereas the other eye remained untreated and served as control. The eyes remained unwashed. The animals were evaluated for ocular effects 24, 48, and 72 h post-exposure using fluorescein staining. Effects noted were graded according to the Draize Scoring System and revealed mean cornea, iris, and chemosis scores over 24, 48 and 72 h out of all six animals of zero. The respective conjunctivae score was 0.22 and the effects observed were fully reversible within 48 h. The animals did not exhibit any abnormal clinical signs for the duration of the study. In conclusion, the test item was not irritating to the eye under the conditions of the test.

Justification for selection of skin irritation / corrosion endpoint:
The key study was selected for assessment.

Justification for selection of eye irritation endpoint:
The key study was selected for assessment.

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.