D-Glucopyranose, oligomeric, heptyl glycosides

Endpoint summary

Description of key information

Skin irritation (OECD 439): not irritating
Eye irritation (OECD 405): corrosive to eyes

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20-23 Mar 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.46 (In Vitro Skin Irritation: Reconstructed Human Epidermis Model Test)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Groupe interministeriel des produits chimiques, Ivry sur Seine, France

Species:

human

Strain:

other: SkinEthic model, in vitro human reconstructed epidermis

Details on test animals or test system and environmental conditions:

TEST SKIN MODEL
- Source: SkinEthic, Lyon, France

TEST METHOD
Skin Ethic RHE/S/17:
0.5 cm² reconstructed epidermis of normal human keratinocytes. Cells are grown on inert polycarbonate filter on chemically defined medium, airlifted for 17 days. Irritant materials are identified by their ability to penetrate the stratum corneum and to damage the underlaying cell layers which is determined through a decrease in cell viability as determined by MTT reduction assay.

ADAPTATION TO CELL CULTURE CONDITIONS
Upon receipt, tissues were transferred into 6-well plates containing 2 mL of growth medium in a humidified incubator for at least 1 h (37 ± 1 °C, 5% CO2) before use.

INCUBATION CONDITIONS (INCUBATOR)
- Temperature (°C): 37
- CO2 gas concentration (%): 5
- Humidity: saturated

Type of coverage:

open

Preparation of test site:

other: Intact reconstructed epidermis

Vehicle:

other: PBS

Controls:

other: concurrent control tissues treated with PBS served as negative controls, positive controls were exposed to 5% SDS.

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 16 ± 2 mg

POSITIVE CONTROL SUBSTANCE:
- Positive control substance: SDS, 5 % (v/v), 16 ± 0.5 µL

Duration of treatment / exposure:

42 ± 1 min

Observation period:

Not applicable. Post-treatment incubation period: 42 ± 1 h.

Number of animals:

Not applicable. The test was performed in triplicates for each treatment and control group.

Details on study design:

TEST SITE
- Area of exposure: 0.5 cm²
REMOVAL OF TEST SUBSTANCE
- Washing: the test item was washed from the epidermises with phosphate buffered saline.
- Time after start of exposure: 42 ± 1 min
- Post-treatment incubation period: 42 ± 1 h

Irritation / corrosion parameter:

other: other: cell viability (%)

Value:

100

Remarks on result:

other:

Remarks:

Basis: other: mean value of negative controls (PBS). Time point: 42 min exposure, 42 h incubation. Reversibility: other: not applicable. (migrated information)

Irritation / corrosion parameter:

other: other: cell viability (%)

Value:

114.8

Remarks on result:

other:

Remarks:

Basis: other: mean value of test item (pure). Time point: 42 min exposure, 42 h incubation. Reversibility: other: not applicable. (migrated information)

Irritation / corrosion parameter:

other: other: cell viability (%)

Value:

2.9

Remarks on result:

other:

Remarks:

Basis: other: mean values of positve control (SDS, 5%). Time point: 42 min exposure, 42 h incubation. Reversibility: other: not applicable. (migrated information)

Table 1: MTT assay after 42 min exposure, 42 h incubation exposure

	Negative control			Positive control			Test item			Dead Ep.
Tissue sample	1	2	3	1	2	3	1	2	3
OD540	1.503 1.512 1.533	1.321 1.308 1.321	1.405 1.400 1.414	0.031 0.035 0.033	0.042 0.044 0.045	0.046 0.047 0.049	1.877 1.893 1.903	1.613 1.611 1.623	1.562 1.564 1.579	0.083 0.064 0.060
OD540(mean)	1.516	1.317	1.406	0.033	0.044	0.047	1.891	1.616	1.568	0.069
OD540(mean values of replicates)	1.413			0.041			1.692			0.069
Viability (%)	100			2.9			119.7			4.9

 

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: 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:

02 Jun - 22 Jul 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

adopted in 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

adopted in 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Groupe interministeriel des produits chimiques, Ivry sur Seine, France

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hypharm, Roussay, France
- Age at study initiation: 11 or 12 weeks
- Weight at study initiation: 1.90-2.28 kg
- Housing: individually in conventional air conditioned animal husbanding
- Diet: tap water, ad libitum
- Water: foodstuff (Safe-112), ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 30-70
- Air changes (per hr): at least ten
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 02 Jun 2014 To: 30 Jun 2014

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye served as control

Amount / concentration applied:

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

Duration of treatment / exposure:

single application without washing

Observation period (in vivo):

Up to 21 days
Reading time points: 1, 24, 48 and 72 h and 7, 14 and 21 days

Number of animals or in vitro replicates:

3 females

Details on study design:

SCORING SYSTEM: Draize score system

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 2

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

ca. 1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

ca. 1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

ca. 1.7

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

probability of moderate irritation

Irritant / corrosive response data:

During the study the following moderate to important and partially reversible ocular lesions have been observed:
-conjunctivae: a moderate redness, noticed 24 h after the test substance instillation and totally reversible by Day 7, associated with slight to important chemosis, noted 24 h after the test item instillation and totally reversible by Day 7.
-iris: a congestion or haemorrage, noted 1 h or 24 h after the test item instillation and totally reversible between Days 7 and 14.
-cornea: a moderate corneal opacity, detected 24 h after the test substance instillation and totally reversible by Day 7 in two animals but persisting until the last day of the test (Day 21) with same intensity (grade 2) in the last animal.
Finally, a corneal neovascularization was noted on Day 14 and Day 21 in the same animal. In addition, a corneal oedema was observed in that animal on Day 7.

Table 1 Individual and mean scores of conjuctivae, iris and cornea

Animal N.	Time after treatment	Conjuctivae		Iris	Cornea
		Chemosis	Redness	Lesion	Opacity
1	24 h	3	2	2	2
	48 h	1	2	2	2
	72 h	1	2	2	2
	Mean	1.7	2	2	2
2	24 h	1	2	1	2
	48 h	1	2	1	2
	72 h	1	2	1	2
	Mean	1	2	1	2
3	24 h	2	2	2	2
	48 h	1	2	2	2
	72 h	2	2	2	2
	Mean	1.7	2	2	2

 

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: Eye Dam. 1, H318
DSD: Xi, R41

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

An in vitro skin irritation study is available for D-Glucopyranose, oligomeric, heptyl glycoside. In this study, a human reconstructed epidermis (SkinEthic) model was used to investigate the effects of the undiluted test item on the viability of the epidermal keratinocytes (Seppic, 2014) according to OECD guideline 439 and GLP.

After 42-min exposure to the test substance, the cellular viability was 114.8% compared to the negative control (100%). Since the mean relative tissue viability was ≥ 50% after 42 minutes treatment, the test substance was considered to be non-irritant to human skin under the conditions of this assay.

Eye irritation

One in vivo study investigating the eye irritation potential of D-Glucopyranose, oligomeric, heptyl glycoside is available (Seppic, 2014). In this study, the unchanged test material was placed into one respective eye of three female rabbits. The other eye remained untreated and served as control. The eyes were examined and scored 24, 48 and 72 h after application. Instillation of the test substance into the eyes of the animals resulted in a moderate redness of the conjuctivae, noticed 24 h after the treatment and totally reversible on day 7, associated with slight chemosis, noted at 24 h and fully reversible on Day 7; congestion or haemorrhage of the iris were noted 1 h or 24 h after the test item instillation and totally reversible between Days 7 and 14; moderate corneal opacity, was detected 24 h after the test substance instillation and totally reversible on Day 7 in two animals but persisting until the last day of the test (day 21) with same intensity (grade 2) in the last animal.

In addition a corneal neovascularization was noted on Day 14 and Day 21 in one animal. Finally, a corneal oedema was observed in the same animal on Day 7. Based on these results, the test substance is considered to be a severe eye irritant.

In addition, three HET CAM tests are available which are not officially accepted for regulatory purposes. However, the results obtained from those studies support the observations from the in vivo study.

Respiratory tract

This information is not available and not mandatory according to Regulation (EC) No. 1907/2006.

 

Justification for selection of skin irritation / corrosion endpoint:
There is only one study available.

Justification for selection of eye irritation endpoint:
There is only one officially accepted study available. The other studies are HET CAM tests which can only be of supportive character.

Effects on eye irritation: corrosive

Justification for classification or non-classification

The available data on skin irritation/corrosion of D-Glucopyranose, oligomeric, heptyl glycoside do not meet the criteria for classification according to Regulation (EC) No 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification. On the basis of the available data on eye irritation/corrosion D-Glucopyranose, oligomeric, heptyl glycosides has to be classified as Eye Dam.1, H318 according to Regulation (EC) No 1272/2008 and as Xi, R41 according to Directive 67/548/EEC