reaction mass of 3,6,9,12-tetraoxotridecan-1-ol and 3,6,9,12,15-pentaoxahexadecan-1-ol

Endpoint summary

Description of key information

Multiple studies available indicating results from no irritancy to slight skin irritancy.

Multiple studies available indicating results from no irritancy to slight eye irritancy (mild conjunctival redness only, resolved within 72 hours)

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:

migrated 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: Scientifically reliable study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Box reason, conventional breeding
- Age at study initiation: 3 - 5 Months
- Weight at study initiation: 2.1 - 2.5 kg
- Housing: in a fully air-conditioned rooms in individual cages (Battery cages)
- Diet: Altromin 2123 maintenance diet - rabbit Altomin GmbH, Lage / Lippe, ad libilum and hay (approximately 15g per day)
- Water: deionized, chlorinated water from automated watering ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3 °C
- Humidity: 50 +/- 20%
- Photoperiod: 12 hours a day

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

0.5 ml of the undiluted substance.

Duration of treatment / exposure:

4 hours.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Approximately 24 hours prior to the experiment start 3 rabbits in the dorsal region were of trunk with an electric hair clipper with an area of approximately 25 cm2 depilated. Only animals with intact skin were used.
- Type of wrap if used: Each animal was given a wound plaster with 2.5 x 2.5 cm coarse pulp edition (special design the company, Beiersdorf AG, Hamburg) were prepared and fixed on the skin site. Area was then covered with a semiocclusive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the remaining was test substance was gentlyremoved with tap water.

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hour observations

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hour observations

Score:

0

Max. score:

4

One hour after removal of the patch was barely visible on two animals. Erythema observed. 24 hours after the administration no symptoms of irritation were observed.

Time after removal of patch	1 hr	24hr	48hr	72hr
Animal number	1 2 3	1 2 3	1 2 3	1 2 3
Erythema and Eschar	1 1 0	0 0 0	0 0 0	0 0 0
Oedema	0 0 0	0 0 0	0 0 0	0 0 0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

In a guideline skin irritation study, the substance methyl tetraglycol caused no irritation over the observation period 24 -72 hours following application of the substance.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Scientifically reliable study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Principles of method if other than guideline:

No further information available.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.5 - 2.6 kg
- Housing: In individual cages in air-conditioned spaces (Battery cages
- Diet: Altromin 2123 Haltungsdilt - rabbits Altromin GmbH Lage / Lippe, ad llbitum and hay (about 15g)
- Water: deionized water ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20±3 °C
- Humidity: 50 +/-20 %
- Photoperiod: 12 hours a day

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

not specified

Controls:

not specified

Amount / concentration applied:

Dorsal area

Duration of treatment / exposure:

4 hours

Observation period:

No further information available.

Number of animals:

3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Time after removal of patch	30 - 60 minutes	24 hours	48 hours	72 hours
Animal number	1, 2 & 3	1, 2 & 3	1, 2 & 3	1, 2 & 3
Erythema and eschar	0, 0, 0	0, 0, 0	0, 0, 0	0, 0, 0
Edema	0, 0, 0	0, 0, 0	0, 0, 0	0, 0, 0

Interpretation of results:

no data

Remarks:

Migrated information Criteria used for interpretation of results: not specified

Executive summary:

In a well reported guideline study skin irritation study, no effects were seen with the substance 2 -(2 -(2 -methoxyethoxy)ethoxy)ethanol.

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Scientifically reliable study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hoechst AG, Box reason, conventional breeding
- Age at study initiation: 3 - 5 Months
- Weight at study initiation: 3.1 - 4.4 kg
- Housing: in air-conditioned rooms in individual cages (Battery cages)
- Diet: Altromin 2123 Haltungsdiat - rabbits Altromin GmbH, Lage / Lippe, ad libitum and hay (about 15g daily)
- Water: deionized, chlorinated water from autonomic watering, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20 +/- 3°C
- Humidity: 50 +/- 20%
- Photoperiod: 12 hours a day

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye in each case served as a control

Amount / concentration applied:

0.1 ml of methyltetraglycol was given as a single dose in the conjunctival sac of the left eye.

Observation period (in vivo):

The assessments of the eyes were made 1, 24, 48 and 72 hours after application of the test substance.

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours

TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

An hour after the administration revealed the conjunctiva and slight swelling markedly injected blood vessels. 24 hours post-administration the conjunctiva of two animals showed distinct hyperemia of blood vessels and diffuse staining crimson were observed. 48 post-adiminstration all irritative symptoms had fully reversed.

Individual findings

Time post application	1h	24h	48h	72h
Animal number	1 2 3	1 2 3	1 2 3	1 2 3
Conjunctival swelling	1 1 0	0 0 0	0 0 0	0 0 0
Conjunctival redness	1 1 1	2 0 1	0 0 0	0 0 0
Iris	0 0 0	0 0 0	0 0 0	0 0 0
Cornea	0 0 0	0 0 0	0 0 0	0 0 0
Fluorescein Test		0 0 0		0 0 0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

In a guideline eye irritation study using the substance methyltetraglycol, no corneal, iris or chemosis response was seen. Slight conjunctival redness was seen with an average score of 0.33 across the three observation timepoints of 24, 48, and 72 hours, but these effects fully resolved across all three animals by the time of the 48 hour observation. On this basis, the substance is regarded as not irritating for classification purposes.

Reference 2

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Remarks:

Scientifically reliable study.

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 3 - 5 months
- Weight at study initiation: 2.8-3.l kg
- Housing: in a fully air-conditioned rooms in Einzelkafigen (Battery cages)
- Diet: Altromin 2123 Haltungsdiit - rabbits Altromin GmbH, Lage / Lippe, ad libitum and hay (about two cups of coffee 15g)
- Water: deionized, chlorinated water from automatic watering entities, ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature: 20±3 °C
- Humidity: 50 ± 20 %
- Photoperiod: 12 hours a day

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated eye was used in each case as a control.

Amount / concentration applied:

0.1 ml of triethylene was applied once into the conjunctival sac of the left eye.

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

No data

Number of animals or in vitro replicates:

3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0.56

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24, 48, 72 hours

Score:

0

Max. score:

4

INDIVIDUAL FINDINGS:

Time post-application	1h	24h	48h	72h
Animal number	1 2 3	1 2 3	1 2 3	1 2 3
conjunctival swelling	1 1 1	0 0 0	0 0 0	0 0 0
conjunctival redness	1 2 1	1 1 2	0 0 1	0 0 0
Iris	0 0 0	0 0 0	0 0 0	0 0 0
Corneal opacity	0 0 0	0 0 0	0 0 0	0 0 0
Fluorescein-Test		0 0 0		0 0 0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Executive summary:

In a guideline eye irritation study using the substance 2 -(2 -(2 -methoxyethoxy)ethoxy)ethanol, no corneal, iris or chemosis response was seen. Slight conjunctival redness was seen with an average score of 0.55 across the three observation timepoints of 24, 48, and 72 hours, but these effects fully resolved across all three animals by the time of the 72 hour observation. On this basis, the substance is regarded as not irritating for classification purposes.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A number of valid skin irritation studies are available using the substances methyl triglycol and methyl tetraglycol, two major components of this UVCB/multicomponent substance, and mixtures containing significant amounts of these substances. The majority of the animal studies using rabbits indicate no irritation response, although some indicate transient response, primarily erythema with no odema seen. A human volunteer study also showed a slight irritation response.

A number of valid eye irritation studies are available using the substances methyl triglycol and methyl tetraglycol, two main components of this UVCB/multicomponent substance, and mixtures containing significant amounts of these substances. These show consistent results with no observable iritis, corneal effects or chemosis observed at any observation point. The only observed effect is mild to moderate transient conjunctival redness (maximum observed value in any animal score 2, with average values in the range 0 to 0.6). These effects are consistently resolved within 72 hours.

Based on observations from the lower members, higher molecular weight species in this homologous series of polyalkylene glycol methyl ethers will show similar potential for irritancy so these results can be considered representative of this UVCB/multicomponent substance. These conclusion for skin and eye irritancy potential are supported by the read across justification document attached to chapter 13 of the lead registrant's dossier.

Justification for classification or non-classification

SKIN IRRITATION: Of those studies available that provide sufficient information to compare to the classification criteria, the data indicate that the response required to trigger classification for acute skin irritation effects is not met. This is confirmed by the response in humans. Classification is clearly not required.

EYE IRRITATION: Of those studies available that provide sufficient information to compare to the classification criteria, the data indicate that the response required to trigger classification for acute skin irritation effects is not met. Only mild and transient conjunctival redness is seen and this effect normally resolves within 72 hours or less. Classification is clearly not required.