propylidynetrimethanol, ethoxylated, esters with acrylic acid and its reactions products with dibutylamine

Endpoint summary

Description of key information

Skin
Rabbit, 4h, semiocclusive: slightly irritating (BASF AG 1993, according to OECD 404 and GLP)
Rabbit, 4h, semiocclusive: not irritating (CrayValley 1993, according to EU method B.4 and GLP)
Rabbit, 24h, occlusive: slightly irritating (BASF AG, 1994, according to Fed. Reg. and GLP)
Rabbit, 24h, occlusive: not irritating (BASF Japan, 1997, according to Code of Federal Regulations, Title 16, Section 1500.41 and GLP)
Eye
Rabbit, substance not washed out:  irritating (BASF AG 1993, according to OECD 405 and GLP)
Rabbit, substance not washed out, irritating (Cray Valley 1994, according to OECD 405 and GLP)
Respiratory System
No data available

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:

1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted May 12, 1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

adopted September 19, 1984

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

Vienna White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Gaukler; D-W6050 Offenbach, FRG
- Age at study initiation: young adult
- Weight at study initiation: 3.18 - 3.59kg
- Housing: single in stainless steel cages with wire mesh floors (40x51cm)
- Diet (e.g. ad libitum): Kliba lab.diet 341 ad lib. (app. 130g / animal / day)
- Water (e.g. ad libitum): 250ml tap water / day
- Acclimation period: at least 1 week

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

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5ml / rabbit

Duration of treatment / exposure:

4h

Observation period:

8 days
observations: 1h after removal of dressing, 1, 2, 3, 8 days after application

Number of animals:

3 females

Details on study design:

TEST SITE
- Area of exposure: 2.5 X 2x5 cm
- Type of wrap if used: test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, D-W6750 Kaiserslautern) and Fixomull@ Stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): at the end of the exposure period, using Lutrol and Lutrol/water (1 : 1)
- Time after start of exposure:4h

SCORING SYSTEM: Draize, as described in OECD guideline 404

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean day 1-3

Score:

1.3

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: scaling observed on day 8

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean day 1-3

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 8 days

Remarks on result:

other: scaling observed on day 8

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean day 1-3

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48h

Remarks on result:

other: scaling observed on day 8

Irritation parameter:

edema score

Basis:

mean

Remarks:

all animals

Time point:

other: day 1-8

Score:

0

Max. score:

4

Interpretation of results:

slightly irritating

Remarks:

Migrated information

Conclusions:

Under the test conditions chosen and considering the described findings the test substance does not give indication of an irritant property to the skin.

Executive summary:

The potential of the test substance to cause acute dermal irritation or corrosion was assessed by a single topical application of 0.5 ml to the intact skin of 3 White Vienna rabbits for 4 hours under semiocclusive dressing. The average score (24 to 72 hours) for irritation was calculated to be 0.9 for erythema and 0.0 for edema. The skin reactions were reversible within 8 days, thus the study was terminated.

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:

1993

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 1987

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

adopted 1984

GLP compliance:

yes

Species:

rabbit

Strain:

Vienna White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Gaukler, Offenbach, Germany
- Age at study initiation: young adult females
- Weight at study initiation: 3.1 - 3 5kg
- Housing: individually in stainless steel cages with wire mesh walk floors (40 X 51cm)
- Diet (e.g. ad libitum): KLIBA lab diet 341 ad lib. (app. 130g/animal/day)
- Water (e.g. ad libitum): tap water ad lib. (app. 250ml/day)
- Acclimation period: at least 1 week

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

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated eye of same animal

Amount / concentration applied:

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

Duration of treatment / exposure:

once, substance not washed out

Observation period (in vivo):

8 days (study terminated after complete reversion of all effects)
observations after 1h, 24h, 48h, 72h, 8 days

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
not washed out

SCORING SYSTEM: see additional information

TOOL USED TO ASSESS SCORE: no data

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 1h - 8 days

Score:

0

Max. score:

2

Remarks on result:

other: no effects on the iris were observed

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 24 - 72h (mean)

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal: #2+#3

Time point:

other: 24-72h (mean)

Score:

1

Max. score:

2

Reversibility:

fully reversible within: 8 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 24h - 72h (mean)

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 72h

Irritation parameter:

conjunctivae score

Basis:

animal: #2 + #3

Time point:

other: 24 - 72h (mean)

Score:

2.7

Max. score:

3

Reversibility:

fully reversible within: 8 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: 24h - 72h (mean)

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal: #2 + #3

Time point:

other: 24h-72h (mean)

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72h (animal 2) or 8 days (animal 3)

Readings	Animal	Cornea		Iris	Conjunctiva			Symptoms
		Opacity	Area		Redness	Swelling	Discharge
1h	1	0	0	0	3	1	2
	2	0	0	0	2	1	2
	3	0	0	0	2	1	2
24h	1	0	0	0	2	0	0
	2	1	4	0	3	2	2	SR, DB
	3	1	3	0	3	1	2	SR
48h	1	0	0	0	1	0	0
	2	1	3	0	3	1	1	SR
	3	1	2	0	3	1	1	SR
72h	1	0	0	0	0	0	0
	2	1	3	0	3	1	1	SR
	3	1	2	0	2	1	0	SR
8 D	1	0	0	0	0	0	0
	2	0	0	0	0	0	0	SR
	3	0	0	0	0	0	0	SR

SR: small retractions in the eyelids

DB: discharge of blood

Interpretation of results:

irritating

Remarks:

Migrated information

Conclusions:

Under the test conditions chosen and considering the described findings, the test substance gives indication of an irritant property to the eye.

Executive summary:

The potential of the test substance to cause damage to the conjunctiva, iris, or cornea was assessed in 3 white Vienna rabbits, subjected to a single ocular application of 0.1ml of the test substance on day 0 . The average score (24 to 72h) for irritation was calculated to be 0.7 for corneal opacity, 0.0 for iris, 2.1 for conjunctivae redness, and 0.7 for chemosis. The findings were reversible in all animals within 8 days, thus the study was terminated.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

There are valid in-vivo data available for the assessment of the skin and eye irritation potential of Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with 1-Butanamine, N-butyl-.

Skin

In an acute dermal irritation or corrosion study according to OECD 404 and GLP, 0.5 ml of the test substance were topically applied to the intact skin of 3 White Vienna rabbits for 4 hours under semiocclusive dressing (BASF AG 1993). The average score (24 to 72 hours) for irritation was calculated to be 0.9 for erythema and 0.0 for edema, thus the test substance was only slightly irritating in this assay. The skin reactions were reversible within 8 days, thus the study was terminated.

In a second in vivo study according to Directive 84/449/EEC (01 No. L251, 19.9.84), Part B, Method BA. Acute toxicity (skin irritation) and GLP (CrayValley 1993), three rabbits were each administered a single dermal dose of 0.5 ml of the test substance for 4 hours under semiocclusevi dressing. Since no dermal reactions were observed for four days, the study was terminated.

Two further studies are available where rabbits were treated with the test substance on abraded and non-abraded skin areas for 24h under occlusive conditions. Due to the harsh conditions compared to current guidelines and because two valid studies are available, the results were only used as supplemental information.

A single dose of 0.5 ml of the test substance applied to a 6 cm² scarified or non-scarified clipped area of the skin of 6 male New Zealand White rabbits (BASF AG 1994) caused only slight irritation. The test substance was held in contact with the skin for 24 hours by means of an occlusive hypoallergenic dressing. Cutaneous reactions were observed approximately 24 and 72 hours

after application of the test substance. Slight to marked erythema was observed on all animals 24 hours after application of the test substance. Reactions were slightly more important on the scarified sites. At the 72-hour reading, erythema persisted on 1 animal and on 4 animals at the non-scarified and the scarified sites, respectively. The Cutaneous Primary Irritation index was: 1.4. Since the animals were only observed for 72h, reactions persisted in a few rabbits until the end of the study. All other studies showed reversibility at the latest after 8 days, and a similar result would have been expected for this study, had the observation period been sufficiently long.

Six rabbits were each administered a dermal dose of 0.5 ml of the test substance to one intact and one abraded skin site and observed for three days (BASF Japan 1997). The method followed was that described in Code of Federal Regulations, Title 16, Section 1500.41. A single occlusive application to intact and abraded rabbit skin for twenty-four hours elicited no dermal irritation.

The Primary Irritation Index (PII) was calculated to be 0.

Eye:

3 white Vienna rabbits were subjected to a single ocular application of 0.1ml of the test substance on day 0 in a GLP study according to OECD 405 (BASF AG 1993) . The average scores (24 to 72h) for the first rabbit were calculated to be 0.0 for corneal opacity, 0.0 for iris, 1.0 for conjunctivae redness, and 0.0 for chemosis. For rabbits no. 2 and 3 the scores were calculated to be 1.0 for corneal opacity, 0.0 for iris, 2.7 for conjunctivae redness, and 1.0 for chemosis. The findings were reversible in all animals within 8 days, thus the study was terminated.

In another OECD 405 study according to GLP (Cray Valley 1994), a single instillation of the test material to the non-irrigated eye of six New Zealand White rabbits produced areas of diffuse to translucent corneal opacity (mean scores 24 -72h ranged between 0.0 and 1.7), iridial inflammation (mean scores 0.0 - 1.0), moderate conjunctival irritation (mean scores 0.3 - 3.0), and chemosis (mean scores 0.3 - 2.0). Other effects noted were slight vascularisation of the cornea and petechial haemorrhage of the nictitating membrane. One treated eye appeared normal 48 hours after treatment and five treated eyes appeared normal fourteen days after treatment.

Effects on eye irritation: irritating

Justification for classification or non-classification

The available data indicate only a very slight irritating potential of Propylidynetrimethanol, ethoxylated, esters with acrylic acid, reaction products with 1-Butanamine, N-butyl-, and the scores obtained in any of the test do not justify classification according to 67/548/EEC or CLP/EU-GHS.

The results obtained in the two OECD 405 studies fulfill the requirements to be classified as R36 acc. to EU criteria and as Category 2A according to CLP/EU-GHS criteria, since effects were reversible after 8 -14 days.