[(butoxymethylethoxy)methylethoxy]propan-1-ol

Endpoint summary

Description of key information

GLP-studies according to OECD guidelines 404 and 405 are available for tripropylene glycol butyl ether. This data is supported by non-GLP studies equivalent to OECD guidelines 404 and 405.

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, Borchen, Germany
- Age at study initiation: about 7 months
- Weight at study initiation: 3.20-3.39 kg
- Fasting period before study: none
- Housing: singel housing in stainless steel wire mesh cages with gating
- Diet: Kliba-Laboratory diet, Provima Kliba SA, Kaiseraugst, Swiss ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12 hrs

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Controls:

other:

Amount / concentration applied:

undiluted

Duration of treatment / exposure:

4 hour(s)

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: upper third of the back or flanks
- Type of wrap if used: semiocclusive dressing


REMOVAL OF TEST SUBSTANCE
- Washing (if done): lutrol/water 1:1
- Time after start of exposure: 4h


SCORING SYSTEM:
Erythema and Eschar Formation:
0 = No erythema
1 = Very slight erythema (barely perceptible)
2 = Well defined erythema
3 = Moderate to severe erythema
4 = Severe erythema (beet-redness) to slight, eschar formation (injuries in depth)

Edema Formation:
0 = No edema
1 = Very slight edema (barely perceptible)
2 = Slight edema (edges of area well defined by definite raising)
3 = Moderate edema (raised approx. 1 mm)
4 = Severe edema (raised more than 1 mm and extending beyond the area of exposure)

Irritation parameter:

erythema score

Basis:

mean

Remarks:

(animal 1-3)

Time point:

other: 24 - 48 - 72 h

Score:

1.6

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: see table below for details

Irritation parameter:

edema score

Basis:

mean

Remarks:

(animal 1-3)

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Other effects:

Slight to moderate erythema, in 1 animal extending beyond the area of exposure, was observed in all animals during the course of the study. No edema was noted. The cutaneous reactions were reversible in all animals within 8 days after removal of the patch at latest. The average score (24 to 72 hours) for irritation was calculated to be 1.6 for erythema and 0.0 for edema.

Readings	Animal	Exposure period: 4 h
		Erythema	Edema	Additional findings
1 h	1	1	0
	2	2	0
	3	2	0
24 h	1	2	0	15
	2	2	0
	3	2	0
48 h	1	2	0	15
	2	2	0
	3	1	0
72 h	1	1	0
	2	2	0
	3	0	0	SD
8 d	1	0	0
	2	0	0
Mean 24h, 48h, 72 h	1	1.7	0
	2	2.0	0
	3	1.0	0
Mean		1.6	0

Symbols:

15  = Erytema extending beyond the area of exposure

SD = Study discontinued because the animal was free of symptomes

Interpretation of results:

GHS criteria not met

Remarks:

Criteria used for interpretation of results: EU

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Centre Lago S.A.,01540 Vonnas, France
- Age at study initiation: about 5 months
- Weight at study initiation: 3.02-3.36 kg
- Fasting period before study: none
- Housing: singel housing in stainless steel wire mesh cages with gating
- Diet: Kliba-Laboratory diet, Provima Kliba SA, Kaiseraugst, Swiss ad libitum
- Water: Tap water ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12 hrs

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye

Amount / concentration applied:

undiluted
Amount applied: 0.1 ml

Duration of treatment / exposure:

24 hrs

Observation period (in vivo):

72 hrs

Number of animals or in vitro replicates:

3

Details on study design:

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


SCORING SYSTEM:
Cornea opacity (op): Degree of density (the most dense area is taken for reading)

0 = No ulceration or opacity
1 = Scattered or diffuse areas of opacity (other than slight dulling of normal lustre) details of iris clearly visible
2 = Easily discernible translucent area, details of iris slightly obscured
3 = Nacreaous area, no details of iris visible, size of pupil barely discernible
4 = Opaque cornea, iris not discernible throught the opacity

Area of cornea involved (ar):
1 = > 0 <= 1/4
2 = > 1/4 < 1/2
3 = > 1/2 < 3/4
4 = > 3/4

Iris:
0 = Normal
1 = Merkedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia or injection, any of these observations or combination of any thereof, iris still reacting to light (sluggish reaction is positive)
2 = No reaction to light, haemorrhage, gross destruction (any or all of these)

Chemosis (sw):
Lids and/or nictating membranes
0 = no swelling
1 = Any swelling abnormal (includes nictitating membranes)
2 = Obvious swelling with partial eversion of lids
3 = Swelling of lids about half closed
4 = Swelling of lids more than half closed

Discharge (di):
0 = No discharge
1 = Any amount different from normal (does not include small amounts observed in inner canthus of normal animals)
2 = Discharge with moistening of the lids and hairs just adjacent to lids
3 = Discharge with moistening of the lids and hairs and considerable area around the eye

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

(animal 1-3)

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Irritation parameter:

iris score

Basis:

mean

Remarks:

(animal 1-3)

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects observed

Irritation parameter:

conjunctivae score

Basis:

mean

Remarks:

(animal 1-3)

Time point:

other: 24 - 48 - 72 h

Score:

0.3

Max. score:

3

Reversibility:

other: all 3 animals showed redness (score 2) at the 1-h reading; redness was reversible within 48 h; see table below for details

Irritation parameter:

chemosis score

Basis:

mean

Remarks:

(animal 1-3)

Time point:

other: 24 - 48 - 72 h

Score:

0

Max. score:

4

Reversibility:

other: all 3 animals showed chemosis (2 animals: score 1; 1 animal: score 2) at the 1-h reading; chemosis was reversible within 24 h; see table below for details

Readings	Animal	Cornea		Iris	Conjunctiva			Additional findings
		op	ar		red	ch	di
1 h	1	0	0	0	2	2	3
	2	0	0	0	2	1	2
	3	0	0	0	2	1	2
24 h	1	0	0	0	1	0	0
	2	0	0	0	0	0	0
	3	0	0	0	2	0	0
48 h	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	0	0	0
72 h	1	0	0	0	0	0	0
	2	0	0	0	0	0	0
	3	0	0	0	0	0	0
Mean 24 -72 h	1	0		0	0.3	0
	2	0		0	0.0	0
	3	0		0	0.7	0
Mean		0		0	0.3	0

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

EU-Classification: not irritating

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

All available studies are of acceptable quality (Klimisch rating 1 or 2) and tripropylenbe glycol butyl ether was not irritating to rabbit skin and eyes in all studies.

Skin irritation: In the identified key study (BASF, 2001) study in rabbits, the mean eryythema and edema scores were 1.6 and 0 for the three rabbits tested across all time points of 24, 48 and 72 hours. In the other supporting studies, the mean erythema and edema scores were very much below the cut-off's triggering the skin irritant classification limits.

Eye irritation: In the identified key study (BASF, 2001) study in rabbits, the mean corneal, iris, conjunctival and chemosis scores were 0, 0, 0.3 and 0 for the three rabbits tested across all the time points of 24, 48 and 72 hours. In the other supporting studies, the mean corneal, iris, conjunctival and chemosis scores were below the cut-off's triggering the eye irritant classification limits.

Respiratory irritation: There are no studies available for respiratory irritation, however, in the absence of any irritation noted in the skin and eye irritation studies, tripropylene glycol n-butyl ether is not expected to be a respiratory irrtant.

Justification for selection of skin irritation / corrosion endpoint:
GLP study conducted according to OECD TG 404

Justification for classification or non-classification

Skin irritation: according to EEC Council Directive 67/548/EEC (amended by Directive 83/467/EEC) the mean value of the scores for erythema was less than 2 for all animals tested. According to annex VI of the directive tripropylene glycol butyl ether was not classified as skin irritant. Similarily according to CLP (Guidance to Regulation (EC) no. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures), tripropylene glycol n-butyl ether will not be classified as a skin irritant.

Eye irritation: according to the annex VI of the council directive 67/548 EEC (amended by directive 83/467 EEC) the average cornea scores after 24, 48 and 72 hours were 0 for all animals. The max. average iris score was 0.3 from all animals tested. The highest average score for conjunctiva was 1.7 and for chemosis 1.0. According to EEC criteria no labelling for eye irritancy is required.

Similarily according to CLP (Guidance to Regulation (EC) no. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures), tripropylene glycol n-butyl ether will not be classified as an eye irritant.

Respiratory irritation: There are no studies available for respiratory irritation, however, in the absence of any irritation noted in the skin and eye irritation studies, tripropylene glycol n-butyl ether is not expected to be a respiratory irrtant.