1-O-β-(2 ,3-di-O-alka(e)noyl-6 -O-acetyl-D-mannopyranosyl)-D-erythritol

Endpoint summary

Description of key information

Skin Irritation/Corrosion: Not corrosive but mildly irritating to skin (does not meet the criteria for classification); OECD 404: K. Oba, BS., 2019

Eye Irritation/Corrosion: Not corrosive but mildly irritating to the eye (does not meet the criteria for classification); OECD 405: K. Oba, BS., 2019

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:

07 February - 05 April 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Its a non-GLP study with deviation from OECD 404.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

yes

Remarks:

the temperature and humidity ranges are outside Guideline specifications.

GLP compliance:

no

Remarks:

The experiment was performed in 2007, therefore pre-dating 1st June 2008 cut off after which GLP compliance is necessary for toxicological tests. The report is dated 2019, because this is when the report itself was finalised.

Species:

rabbit

Strain:

other: Kbl:NZW{SPF}

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kitayama Labes Co., Ltd..
- Females (if applicable) nulliparous and non-pregnant: Not stated
- Age at study initiation: 16 - 17 weeks
- Weight at study initiation: 3.37 – 3.82 kg
- Fasting period before study: yes (17 hour)
- Housing: Animals were individually housed in wire mesh cage, 30.5W×49.5D× 33.5H (cm), One animal/cage (during the study).
- Diet (e.g. ad libitum): RC4
(Oriental Yeast, Lot No. 060821)
- Water (e.g. ad libitum): tap water from automated water supply system ad libitum. 

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.0−27.0°C
- Humidity (%): 35.0−75.0%
- Air changes (per hr): 8 or more times air changes per hour
- Photoperiod (hrs dark / hrs light): 12 : 12
IN-LIFE DATES: 27/2/ 2007 – 9/3/2007

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 & 72 hours after patch removal

Number of animals:

3

Details on study design:

One side of a 2.45 cm-sq patch (lint, Hasegawamenkou) was applied with 0.5 mL of undiluted test item, the patch was held in place for 4 hrs in the dorsal skin of each animal. The residual test substance was removed from the test side. Observations was made at 1, 24, 48 & 72 hours after patch removal .

Irritation parameter:

erythema score

Remarks:

plus eschar

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other:

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Remarks:

plus eschar

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Remarks:

plus eschar

Basis:

animal #3

Time point:

24/48/72 h

Score:

>= 1 - <= 2

Max. score:

4

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Remarks:

plus eschar and edema

Basis:

animal #1

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Remarks:

plus eschar and edema

Basis:

animal #2

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of mild irritation

Irritation parameter:

erythema score

Remarks:

plus eschar and edema

Basis:

animal #3

Time point:

other: 1 Hour

Score:

1

Max. score:

4

Reversibility:

not reversible

Remarks on result:

probability of mild irritation

Irritant / corrosive response data:

The substance is not corrosive but was a mild irritant according to the P.D.I.I.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the condition of the study, the primary irritation index (P.D.I.I.) of the test item was 1.4 ('Mild irritant'), following exposure to clipped rabbit skin under semi-occlusive conditions. However, the test item does not meet the criteria for classification according to the Globally Harmonized Classification System or the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

OECD 404 (2019): The irritant or corrosive effects of the test item, was assessed following application to the clipped skin of white New Zealand rabbits. On one side of a 2.45 cm-sq patch (lint, Hasegawamenkou) was applied with 0.5 mL of undiluted test item, the patch was held in place for 4 hrs on the dorsal skin of each animal. The residual test substance was removed from the test side. Observations were made at 1, 24, 48 & 72 hours after patch removal and the skin response scored and the degree of skin irritation was classified according to the categories of Gad and Chengelis method.

Both erythema (score: 1) and  edema (score: 1) were observed on 3 tested sites at 1 hour after removal. At 24 hour after patch removal, erythema (score: 2 or 1) was found on 3 test sites, and edema (score 1) was observed on 3 test sites. Erythema (score 1) was found on 3 test sites at 48 and 72 hours after patch removal, however, all of the edema disappeared at 48 hours.

Based on the conditions of this study, the test item was non-corrosive but caused mild irritation to the rabbits' skin according to the categories of skin irritation by Gad and Chengelis method (P.D.I.I. = 1.4). However, under the conditions of the study, it was concluded that the test item does not meet the criteria for classification according to the Globally Harmonized Classification System or 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)

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:

07th February - 05th April 2007

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

not specified

Remarks:

However, the temperature and humidity ranges are outside Guideline specifications.

GLP compliance:

no

Remarks:

The experiment was performed in 2007, therefore pre-dating 1st June 2008 cut off after which GLP compliance is necessary for toxicological tests. The report is dated 2019, because this is when the report itself was finalised.

Species:

rabbit

Strain:

other: Kbl:NZW[SPF]

Vehicle:

unchanged (no vehicle)

Controls:

other: Untreated one eye

Amount / concentration applied:

0.1ml

Duration of treatment / exposure:

One second

Observation period (in vivo):

1, 24, 48 and 72 hours

Duration of post- treatment incubation (in vitro):

n/a

Number of animals or in vitro replicates:

3

Irritation parameter:

overall irritation score

Basis:

animal: Mean score

Time point:

24 h

Score:

8.8

Max. score:

110

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal: Mean Score

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: Irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal: Mean score

Time point:

72 h

Score:

3.4

Max. score:

110

Reversibility:

other: irriatnt

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

24 h

Score:

8

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

72 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

24 h

Score:

10

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #2

Time point:

72 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

24 h

Score:

8

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

48 h

Score:

4

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of mild irritation

Irritation parameter:

overall irritation score

Basis:

animal #3

Time point:

72 h

Score:

2

Max. score:

110

Reversibility:

other: irritant

Remarks on result:

probability of weak irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

0

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

not fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

animal #2

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: 48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of weak irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

The test item was not corrosive but it was considered to be ‘Minimally irritating’ to rabbit eyes under the conditions of this study.

Table 2. Mean scores ocular irritation in rabbits

No. of animal: 3
Ocular Reactions	Categories of response	Time after application
Conjunctivae		1h	24h	48h	72h
	A.Redness	1.0	1.7	1.0	1.0
	B. Chemosis	2.3	2.0	1.0	0.7
	C. Discharge	2.0	0.7	0	0
	Weighted score: (A+B+C) x 2 = Total maximum score of 20	10.6	8.8	4	3.4
Cornea	A.Opacity-degree of density	0	0	0	0
	B. Area of cornea invloved	0	0	0	0
	Weighted score: (AxBx5) = Total maximum score of 80	0	0	0	0
Iris	A	0	0	0	0
	Weighted scores: Ax5 = Total maximum =10	0	0	0	0
Total possible maximum = Sum of total maximum scores		10.6	8.8	4	3.4

Table 3. Individual ocular irritation in rabbits

Time after application
Ocular Reactions	Categories of response	Animal #1				Animal #2				Animal #3
Conjunctivae		1h	24h	48h	72h	1h	24h	48h	72h	1h	24h	48h	72h
	A.Redness	1	1	1	1	1	2	1	1	1	1.7	1	1
	B. Chemosis	2	2	1	1	3	2	1	1	2.3	2	1	0.7
	C. Discharge	2	1	0	0	2	1	0	0	2	0.7	0	0
	Weighted score: (A+B+C) x 2 = Total maximum score of 20	10	8	4	4	12	10	4	4	10	8	4	2
Cornea	A.Opacity-degree of density	0	0	0	0	0	0	0	0	0	0	0	0
	B. Area of cornea invloved	0	0	0	0	0	0	0	0	0	0	0	0
	Weighted score: (AxBx5) = Total maximum score of 80	0	0	0	0	0	0	0	0	0	0	0	0
Iris	A	0	0	0	0	0	0	0	0	0	0	0	0
	Weighted scores: Ax5 = Total maximum =10	0	0	0	0	0	0	0	0	0	0	0	0
Total possible maximum = Sum of total maximum scores		10	8	4	4	12	10	4	4	10.6	8.8	4	3.4

H: hours(s)

Iris: 0 – 2 numerical scores

Redness and discharge: 0 – 3 numerical scores

Chemosis, opacity-degree of density and area of cornea involved: 0-4 numerical scores

The total possible maximum score is the sum of all scores obtained for the cornea, iris & conjunctivae.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study the test item did not produce any evidence of ocular corrosivity but a reversible mild irritation was observed. However, the test item does not meet the criteria for classification according to the Globally Harmonized Classification System or according to the Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Executive summary:

OECD 405 – 2019: Three healthy female New Zealand White rabbits free from evidence of ocular irritation and corneal abnormalities, were used in the study. A volume of 0.1 mL of undiluted test item was instilled into the conjunctival sac of each animal (3 female rabbits). The upper and lower eyelids were held for  about one second in order to prevent loss of the test item. Ocular reactions for cornea, iris and conjunctiva of the tested eyes were observed at 1, 24, 48 and 72 hours after test item application and scored according to the method of Draize. The control eyes were observed at the same time periods. A 2% aq solution of Sodium fluorescein dye was instilled into the tested eyes 24h after application and then the stained area of the cornea was observed.  All of the tested eyes were photographed at the 24 hours after application. Ocular reaction was irreversible after 72 hours, therefore observation was extended to 7 days after application.

At 1 hour after application, slight conjunctival redness (score: 1), moderate conjunctival swelling (chemosis, score 3), slight conjunctival swelling (score 2), and moderate discharge (score 2) were observed in 3, 1, 2 & 3 test eyes, respectively.

At 24 hour after application, moderate conjunctival redness (score 2), slight conjunctival redness, slight conjunctival swelling and slight discharge (score 1) were observed in 3, 1, 2 & 3 test eyes, respectively.  The discharged disappeared in one animal at 24 hour post application.

At 48 hours post application, ocular irritation was reduced; slight conjunctival redness and slight conjunctival swelling were found in 3 test eyes and discharge in the tested eyes had disappeared.

At 72 hour post application; slight conjunctival redness and slight conjunctival swelling were found in 3 and 2 test eyes, respectively, and the conjunctival swelling disappeared in 1 test eye.

At 7 day post application, the ocular irritation on the test eyes had completely disappeared. No abnormalities were observed in cornea and iris of any of the tested eyes.

It can be concluded that the observed ocular reactions were reversible, therefore, the test item was considered a mild irritant in the categories of the Harmonised integrated classifications system for human health and environmental hazards of chemical substances and mixtures (OEC Series on Testing and Assessment Number 33) to the rabbit eyes under the study conditions.

Under the conditions of the study the test item did not produce any evidence of ocular corrosivity but a reversible (within 7 days) mild irritation was observed. However, the test item does not meet the criteria for classification according to the Globally Harmonized Classification System or according to the 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

Additional information

Eye Irritation/Corrosion:

OECD 405 – 2019: Three healthy female New Zealand White rabbits free from evidence of ocular irritation and corneal abnormalities, were used in the study. A volume of 0.1 mL of undiluted test item was instilled into the conjunctival sac of each animal (3 female rabbits). The upper and lower eyelids were held for about one second in order to prevent loss of the test item. Ocular reactions for cornea, iris and conjunctiva of the tested eyes were observed at 1, 24, 48 and 72 hours after test item application and scored according to the method of Draize. The control eyes were observed at the same time periods. A 2% aq solution of Sodium fluorescein dye was instilled into the tested eyes 24h after application and then the stained area of the cornea was observed.  All of the tested eyes were photographed at the 24 hours after application. Ocular reaction was irreversible after 72 hours, therefore observation was extended to 7 days after application.

At 1 hour after application, slight conjunctival redness (score: 1), moderate conjunctival swelling (chemosis, score 3), slight conjunctival swelling (score 2), and moderate discharge (score 2) were observed in 3, 1, 2 & 3 test eyes, respectively.

At 24 hour after application, moderate conjunctival redness (score 2), slight conjunctival redness, slight conjunctival swelling and slight discharge (score 1) were observed in 3, 1, 2 & 3 test eyes, respectively.  The discharged disappeared in one animal at 24 hour post application.

At 48 hours post application, ocular irritation was reduced; slight conjunctival redness and slight conjunctival swelling were found in 3 test eyes and discharge in the tested eyes had disappeared.

At 72 hour post application; slight conjunctival redness and slight conjunctival swelling were found in 3 and 2 test eyes, respectively, and the conjunctival swelling disappeared in 1 test eye.

At 7 day post application, the ocular irritation on the test eyes had completely disappeared. No abnormalities were observed in cornea and iris of any of the tested eyes.

It can be concluded that the observed ocular reactions were reversible and the test item was considered a mild irritant according to OECD Series on Testing and Assessment Number 33. However, under the conditions of the study the test item did not produce any evidence of ocular corrosivity and does not meet the criteria for classification according to the Globally Harmonized Classification System or according to Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.

Skin Irritation/Corrosion:

OECD 404 (2019): The irritant or corrosive effects of the test item, was assessed following application to the clipped skin of white New Zealand rabbits. On one side of a 2.45 cm-sq patch (lint, Hasegawamenkou) was applied with 0.5 mL of undiluted test item, the patch was held in place for 4 hrs on the dorsal skin of each animal. The residual test substance was removed from the test side. Observations were made at 1, 24, 48 & 72 hours after patch removal and the skin response scored and the degree of skin irritation was classified according to the categories of Gad and Chengelis method.

Both erythema (score: 1) and  edema (score: 1) were observed on 3 tested sites at 1 hour after removal. At 24 hour after patch removal, erythema (score: 2 or 1) was found on 3 test sites, and edema (score 1) was observed on 3 test sites. Erythema (score 1) was found on 3 test sites at 48 and 72 hours after patch removal, however, all of the edema disappeared at 48 hours.

The test item, according to the categories of skin irritation by Gad and Chengelis method (P.D.I.I. = 1.4), was classified as mild irritant. Under the condition of the study, it was concluded that the test item was non-corrosive but caused mild irritation to the rabbits’ skin. However, the test item did not meet the criteria according to the Globally Harmonized Classification System and does not meet the criteria for classsifiaction in accordance with Regulation (EC) No. 1272/2008, relating to the Classification, Labelling and Packaging of Substances and Mixtures.