Registration Dossier

Administrative data

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:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
adopted May 12, 1981
Deviations:
no
Qualifier:
according to
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 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:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Version / remarks:
adopted 1987
Qualifier:
according to
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.