[2-(1-propoxyethoxy)ethyl]benzene

Endpoint summary

Description of key information

Skin corrosion: Substance is not corrosive as it is also not irritating.

Skin irritation: not irritating (read-across from Hyacinth body tested in OECD TG 404)

Eye irritation: not irritating (read-across from Hyacinth body tested in OECD TG 405)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

The skin irritation information of this source substance is used for read across to Hyacinth body #3.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

exposure period was 24 h instead of 4 h, observation time points were 0 and 48 h after patch removal instead of 24, 48 and 72 h.

GLP compliance:

no

Remarks:

pre-GLP

Species:

rabbit

Strain:

New Zealand White

Remarks:

albino

Details on test animals or test system and environmental conditions:

No details provided.

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

electric clipper, avoiding abrasions

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

0.5 ml testing material

Duration of treatment / exposure:

24 hours

Observation period:

48 hours after patch removal

Number of animals:

12 animals - 6 with intact skin and 6 with abraded skin (results for abraded skin are disregarded in this study record).

Details on study design:

TEST SITE:
- Area of exposure: 1x1 inch
- Type of wrap if used: surgical patch, fixed to application site with adhesive tape and entire trunk of rabbits is wrapped with impervious material.

OBSERVATION TIME POINTS:
After 24 hours (directly after exposure) and after 72 hours (48 hours after patch removal).

SCORING SYSTEM:
Method of calculation: Draize (J. Pharmacol. 82 (1944) 377-390).

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 1, 2 and 3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 4 and 6

Time point:

24/48/72 h

Score:

1

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

erythema score

Basis:

other:

Remarks:

score of animal number 5

Time point:

24/48/72 h

Score:

2

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

edema score

Basis:

other:

Remarks:

scores of animal number 1, 2, 3, 4 and 6

Time point:

24/48/72 h

Score:

0

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

edema score

Basis:

other:

Remarks:

score of animal number 5

Time point:

24/48/72 h

Score:

1

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

erythema score

Basis:

other:

Remarks:

score of animal number 3

Time point:

other: 0 h

Score:

0

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 1 and 2

Time point:

other: 0 h

Score:

1

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 4 and 6

Time point:

other: 0 h

Score:

2

Irritation parameter:

erythema score

Basis:

other:

Remarks:

score of animal number 5

Time point:

other: 0 h

Score:

3

Irritation parameter:

edema score

Basis:

other:

Remarks:

scores of animal number 1, 2 and 3

Time point:

other: 0 h

Score:

0

Irritation parameter:

edema score

Basis:

other:

Remarks:

scores of animal number 4, 5 and 6

Time point:

other: 0 h

Score:

1

Irritant / corrosive response data:

The test substance was found to induce some skin irritation effects. After 24 hours exposure very slight to moderate erythema and very slight edema was observed. Dermal effects observed 48 hours after patch removal were very slight or well-defined erythema, slight scaliness and very slight edema.

To be able to derive a CLP classification from skin irritation test results, normally the 24, 48 and 72 hours timepoints (after patch removal) for erythema and edema are used. In this study only the 48 hours timepoint is available for evaluation. As supporting evidence the reading directly after removal of the patch is available (0 hours timepoint) and can be considered the worst-case effect. Based on the available eythema and edema scores and the longer exposure period (24 instead of 4 hours), it is concluded that interpretation for CLP purposes is possible with the current test.

Interpretation of results:

other: not skin irritating

Remarks:

Based on CLP criteria (EC 1272/2008 and its updates)

Conclusions:

Hyacinth body is not an irritant to skin, according to OECD 404.

Executive summary:

The skin irritation potential of Hyacinth body was tested in vivo using 12 New Zealand white rabbits (6 with intact skin and 6 with abraded skin). Study was performed similar to OECD 404 with some deviations on exposure time and observation period and therefore a Klimisch 2 rating was assigned. The test material was applied on the skin under a surgical patch. After an exposure period of 24 hours the patches were removed. Only testing results of 6 animals with intact skin are considered useful for evaluation of skin irritation. The animals were observed only at 48 hours after patch removal and no observations were done at time points of 24 and 72 hours. Effects observed directly upon patch removal were limited. Regarding erythema, 1 animal scored 3, 2 animals scored 2, 2 animals scored 1 and 1 animal scored 0, and regarding edema, 3 animals scored 1 and 3 animals scored 0. The dermal effects observed at 48 hours after patch removal were decreased to none to moderate erythema (1 animal scored 2, 2 animals scored 1 and 3 animals scored 0) and none to slight edema (1 animal scored 1 and 5 animals scored 0). Directly after patch removal only the erythema score for one animal was above the classification threshold (score 3). Although the study was not continued until the complete disappearance of the effects, the effects decreased largely within the 48 hours after patch removal. Given the longer exposure period of 24 instead of 4 hours and the test results obtained, it can be concluded that Hyacinth body is not an irritant to skin.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information derived from analogue

Justification for type of information:

The read across justification is presented in the Irritation / corrosion Endpoint summary. The accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 1, 2 and 3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 4 and 6

Time point:

24/48/72 h

Score:

1

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

erythema score

Basis:

other:

Remarks:

score of animal number 5

Time point:

24/48/72 h

Score:

2

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

edema score

Basis:

other:

Remarks:

scores of animal number 1, 2 and 3

Time point:

24/48/72 h

Score:

0

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

edema score

Basis:

other:

Remarks:

score of animal number 5

Time point:

24/48/72 h

Score:

1

Remarks on result:

other:

Remarks:

24 hours and 72 hours timepoints were not scored

Irritation parameter:

erythema score

Basis:

other:

Remarks:

score of animal number 3

Time point:

other: 0 h

Score:

0

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 1 and 2

Time point:

other: 0 h

Score:

1

Irritation parameter:

erythema score

Basis:

other:

Remarks:

scores of animal number 4 and 6

Time point:

other: 0 h

Score:

2

Irritation parameter:

erythema score

Basis:

other:

Remarks:

score of animal number 5

Time point:

other: 0 h

Score:

3

Irritation parameter:

edema score

Basis:

other:

Remarks:

scores of animal number 1, 2 and 3

Time point:

other: 0 h

Score:

0

Irritation parameter:

edema score

Basis:

other:

Remarks:

scores of animal number 4, 5 and 6

Time point:

other: 0 h

Score:

1

Irritant / corrosive response data:

The test substance was found to induce some skin irritation effects. After 24 hours exposure very slight to moderate erythema and very slight edema was observed. Dermal effects observed 48 hours after patch removal were very slight or well-defined erythema, slight scaliness and very slight edema.

To be able to derive a CLP classification from skin irritation test results, normally the 24, 48 and 72 hours timepoints (after patch removal) for erythema and edema are used. In this study only the 48 hours timepoint is available for evaluation. As supporting evidence the reading directly after removal of the patch is available (0 hours timepoint) and can be considered the worst-case effect. Based on the available eythema and edema scores and the longer exposure period (24 instead of 4 hours), it is concluded that interpretation of the study for CLP purposes is possible with the current test.

Interpretation of results:

other: not skin irritating

Remarks:

Based on CLP criteria (EC 1272/2008 and its updates)

Conclusions:

Skin irritation: not irritating (read-across from Hyacinth body tested in OECD TG 404).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Justification for type of information:

The eye irritation information of this source substance is used for read across to Hyacinth body #3.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

No examination was done 1 hour after instillation, observation for 7 days.

GLP compliance:

no

Remarks:

pre-GLP

Species:

rabbit

Strain:

New Zealand White

Remarks:

albino

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Housing: caged individually
- Other: the animals receive no hay or other extraneous material that might enter the eyes

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL testing material

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

6

Details on study design:

SCORING SYSTEM: Draize and Kelley (1952)

Irritation parameter:

cornea opacity score

Basis:

animal: 1 to 6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal: 1 to 6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal: 1, 2 and 4

Time point:

24/48/72 h

Score:

0.66

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal: 5 and 6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal: 2 to 6

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Slight redness of the conjunctivae in four out of six rabbits and slight swelling (chemosis) of the conjunctivae in one out of six rabbits was noted. After seven days all lesions had cleared up.

Interpretation of results:

other: not eye irritating

Remarks:

Based on CLP criteria (EC 1272/2008 and its updates)

Conclusions:

Under the conditions of this test, Hyacinth body is not considered to be an eye irritant.

Executive summary:

The eye irritation potential of Hyacinth body was tested in vivo using 6 New Zealand white rabbits. A Klimisch 2 rating was assigned as the test was performed similar to OECD 405 but with (acceptable) deviations on the observation period. Prior to instillation, eyes of the animals were examined for visible eye defects. 0.1 mL of testing material per animal was instilled in one eye and the other eye served as control. Eyes were not washed after instillation. Animals were observed at 24, 47, 72 and 7 days after instillation. No cornea and iris effects were noted. Slight redness of the conjunctivae in four out of six rabbits (with a mean (from 24, 48 and 72 hours) score 0.66 in 3 animals and a mean score 1 in one animal) and slight swelling (chemosis) of the conjunctivae in one out of six rabbits (mean score 0.33) were noted. After seven days all lesions had cleared up. Under the conditions of this test, Hyacinth body is not considered to be an eye irritant.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Information derived from analogue

Justification for type of information:

The read across justification is presented in the Irritation / corrosion Endpoint summary. The accompanying files are also attached there.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

cornea opacity score

Basis:

animal: 1 to 6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

iris score

Basis:

animal: 1 to 6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

conjunctivae score

Basis:

animal: 1, 2 and 4

Time point:

24/48/72 h

Score:

0.66

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Reversibility:

fully reversible

Irritation parameter:

conjunctivae score

Basis:

animal: 5 and 6

Time point:

24/48/72 h

Score:

0

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.33

Reversibility:

fully reversible

Irritation parameter:

chemosis score

Basis:

animal: 2 to 6

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

Slight redness of the conjunctivae in four out of six rabbits and slight swelling of the conjunctivae in one out of six rabbits was noted. After seven days all lesions cleared up.

Interpretation of results:

other: not eye irritating

Remarks:

Based on CLP criteria (EC 1272/2008 and its updates)

Conclusions:

Eye irritation: not irritating (read-across from Hyacinth body tested in OECD TG 405).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

The skin and eye irritation is based on read across from Hyacinth body. First the information on Hyacinth body is presented and thereafter the read across justification is presented. The justification document is also attached in this endpoint summary.

Skin irritation

Information on Hyacinth body (CAS# 2556-10-7)

The skin irritation potential of Hyacinth body was tested in vivo using 12 New Zealand white rabbits (6 with intact skin and 6 with abraded skin). Study was performed similar to OECD 404 with some deviations on exposure time and observation period and therefore a Klimisch 2 rating was assigned. The test material was applied on the skin under a surgical patch. After an exposure period of 24 hours the patches were removed. Only testing results of 6 animals with intact skin are considered useful for evaluation of skin irritation. The animals were observed only at 48 hours after patch removal and no observations were done at time points of 24 and 72 hours. Effects observed directly upon patch removal were limited. Regarding erythema, 1 animal scored 3, 2 animals scored 2, 2 animals scored 1 and 1 animal scored 0, and regarding edema, 3 animals scored 1 and 3 animals scored 0. The dermal effects observed at 48 hours after patch removal were decreased to none to moderate erythema (1 animal scored 2, 2 animals scored 1 and 3 animals scored 0) and none to slight edema (1 animal scored 1 and 5 animals scored 0). Directly after patch removal only the erythema score for one animal was above the classification threshold (score 3). Although the study was not continued until the complete disappearance of the effects, the effects decreased largely within the 48 hours after patch removal. Given the longer exposure period of 24 instead of 4 hours and the test results obtained, it can be concluded that Hyacinth body is not an irritant to skin. 

 

Eye irritation

Information on Hyacinth body (CAS# 2556-10-7)

The eye irritation potential of Hyacinth body was tested in vivo using 6 New Zealand white rabbits. A Klimisch 2 rating was assigned as the test was performed similar to OECD 405 but with (acceptable) deviations on the observation period. Prior to instillation, eyes of the animals were examined for visible eye defects. 0.1 mL of testing material per animal was instilled in one eye and the other eye served as control. Eyes were not washed after instillation. Animals were observed at 24, 47, 72 and 7 days after instillation. No cornea and iris effects were noted. Slight redness of the conjunctivae in four out of six rabbits (with a mean (from 24, 48 and 72 hours) score 0.66 in 3 animals and a mean score 1 in one animal) and slight swelling (chemosis) of the conjunctivae in one out of six rabbits (mean score 0.33) were noted. After seven days all lesions had cleared up. Under the conditions of this test, Hyacinth body is not considered to be an eye irritant.

Read-across justification

The skin and eye irritation properties of Hyacinth body #3 (CAS no. 7493-57-4, target) using read across from Hyacinth body (CAS no. 2556-10-7, source)

 

Introduction and hypothesis for the read across

Hyacinth body #3 has a benzyl ring with an ethyl chain to which an acetal is attached and another propyl chain. For this substance no relevant skin irritation data are available. Therefore additional information is used in accordance with Article 13 of REACH where it is said that lacking information should be generated whenever possible by means other than vertebrate animal tests, i.e. applying alternative methods such as in vitro tests, SARs, grouping and read-across.

Hypothesis: Hyacinth body #3 is expected to have the same skin and eye irritating properties as Hyacinth body.

Available information:

Skin irritation: The skin irritation potential of Hyacinth body was tested in vivo in rabbits in a study performed similar to OECD 404. Under the conditions of this test, some erythema and edema effects were observed directly after patch removal. Although the study was not continued until the complete disappearance of the effects, the effects decreased largely within the 48 hours after patch removal. Given the longer exposure period of 24 instead of 4 hours and the test results obtained, it can be concluded that Hyacinth body is not an irritant to skin.

Eye irritation: The eye irritation potential of Hyacinth body was tested in vivo in rabbits in a study performed similar to OECD 405. Slight effects in conjunctivae were noted, which cleared up after seven days. Under the conditions of this test, Hyacinth body is not considered to be an eye irritant.

Target and Source chemical(s)

Chemical structures of the target chemical (Hyacinth body #3) and the source chemical (Hyacinth body) are shown in the data matrix, including physico-chemical properties and toxicological information, thought relevant for skin and eye irritation.

Purity / Impurities

Hyacinth body #3 and Hyacinth body are mono-constituents. The impurities in both target and source are all below 2%.

Analogue justification

According to REACH Annex XI an analogue approach and structural alert information can be used to replace testing when information from different sources provides sufficient evidence to conclude that this substance has or does not have a particular dangerous property. The result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation.

Analogue selection: Hyacinth body was selected as read across analogue based on analogues found in QSAR Toolbox and RIFM and because it is a substance from IFF portfolio.

Structural similarities and differences: The target chemical Hyacinth body #3 and source chemical Hyacinth body have the same backbone (benzyl ring to which an ethyl and an alkyl chain is attached which is interrupted with the same functional acetal group). The structural difference is that the target Hyacinth body #3 has an additional methyl group compared to Hyacinth body.

Absorption: For skin and eye irritation absorption is a parameter which needs to be considered because most of irritant substances first have to be absorbed before cytotoxicity occurs. The target Hyacinth body #3 and the source Hyacinth body have the same absorption characteristics based on both substances being a liquid, based on molecular structure, weight and log Kow. The one methyl group less in Hyacinth body does not significantly change the absorption.

Reactivity: Reactivity is the key parameter for assessing the skin and eye irritation potential. The target chemical Hyacinth body #3 and source chemical Hyacinth body are expected to have the same reactivity, based on the fact that both have the same functional acetal group. The fact that the target substance Hyacinth body #3 has one additional methyl group compared to the source substance will not influence this.

Remaining uncertainties: There are no remaining uncertainties based on the reasoning above.

Conclusions on the skin irritation

When using read across, the result derived should be applicable for C&L and/or risk assessment and be presented with adequate and reliable documentation. For Hyacinth body #3 the skin and eye irritation information can be retrieved from Hyacinth body. The justification is presented in the present document. Hyacinth body #3 is not a skin or eye irritant because Hyacinth body is not a skin and eye irritant, as tested in similar to OECD TG 404 and 405, respectively.

Final conclusion on hazard and C&L: Hyacinth Body #3 is not a skin or eye irritant.

 

Data matrix for the read across from Hyacinth body to Hyacinth body #3

CHEMICAL NAME	Hyacinth body #3	Hyacinth body
Molecular structure
CAS	7493-57-4	2556-10-7
Molecular formula	C13H20O2	C12H18O2
REACH registration	For 2018	For 2018
Einecs	231-327-9	219-868-9
Tanimoto*	1	0.93
Molecular weight	208.30	194.28
Physico-chemical properties
Appearance	Liquid	Liquid
Melting point (˚C)	32.27 (C) <-20 (M)	21.75 (C) <-20 (M)
Boiling point (˚C)	272.67 (C) 263.4 (M)	255.94 (C) 248.2 (M)
Water solubility at 20˚C (mg/L)	49.14 (C) 86.0 (M)	152.3 (C) 453 (M)
Log Kow	3.40 (C) 4.1 (M)	2.91 (C) 3.5 (M)
Human health
Skin irritation	Read across from Hyacinth body	Not skin irritating (OECD TG 404)
Eye irritation	Read across from Hyacinth body	Not eye irritating (OECD TG 405)

For testing data, see the IUCLID under the relevant endpoint. Calculated physico-chemical data were generated with EPISuite (version 4.1). C: calculated value, M: measured at IFF.

*Tanimoto calculation: http://chemmine.ucr.edu/similarity/#

Justification for classification or non-classification

Based on the results of the skin and eye irritation tests performed for the read-across analogue Hyacinth body, it can be concluded that Hyacinth body #3 does not need to be classified as an eye or skin irritant in accordance with the criteria outlined in Annex I of the CLP Regulation (1272/2008/EC) and its updates.