Registration Dossier

Administrative data

Description of key information

Skin (OECD 404): not irritating (0.5 g, rabbit, semi-occlusive, 4 h)
Eye (OECD 405): not irritating (0.1 mL/44 mg, rabbit, single application without washing)

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:
23 Oct - 2 Nov 2007
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 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
adopted 2004
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
adopted Aug 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, the Netherlands
- Age at study initiation: 8-10 weeks
- Weight at study initiation: 1.44-1.62 kg
- Housing: animals were housed individually in cages (56 cm x 44 cm x 37,5 cm) with perforated floors (Scanbur, Denmark)
- Diet: K-H pelleted diet for rabbits (SSNIFF Spezialdiäten GmbH, Soest, Germany), approximately 100 g/day. Hay (Technilab-BMI BV, Someren, the Netherlands) was provided at least 3 times/week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.4-22.4
- Humidity (%): 45-61%
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23 Oct 2007 To: 2 Nov 2007
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
water
Controls:
other: untreated sites of the animals served as the control
Amount / concentration applied:
TEST MATERIAL
- Amount applied: 0.5 g

VEHICLE
- Amount applied: 0.5 mL
(0.5 g test substance was moistened with 0.5 mL vehicle before application)

The test material was ground to a powder using a pestle and mortar prior to weighing.
Duration of treatment / exposure:
4 h
Observation period:
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals:
3 males
Details on study design:
TEST SITE
- Area of exposure: approximately 6 cm² on the dorsal area
- Type of wrap if used: the test substance was applied to a metalline patch (2 cm x 3 cm), which was mounted on Micropore tape that was wrapped around the abdomen and secured with Coban elastic bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the residual test substance was removed from the skin using tap water
- Time after start of exposure: 4 h

SCORING SYSTEM: Draize scoring system
Irritation parameter:
erythema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
edema score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritant / corrosive response data:
No erythema or edema was recorded in any of the animals at any reading time point.
Other effects:
There was no mortality, no clinical signs were observed and the body weight was within the normal range during the study period.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
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:
29 Oct - 16 Nov 2007
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 2002
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Version / remarks:
adopted 2004
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Version / remarks:
adopted Aug 1998
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No. 8147, November 2000, including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Horst, the Netherlands
- Age at study initiation: 9-12 weeks
- Weight at study initiation: 2.02-2.10 kg
- Housing: animals were housed individually in cages (56 cm x 44 cm x 37,5 cm) with perforated floors (Scanbur, Denmark)
- Diet: K-H pelleted diet for rabbits (SSNIFF Spezialdiäten GmbH, Soest, Germany), approximately 100 g/day. Hay (Technilab-BMI BV, Someren, the Netherlands) was provided at least 3 times/week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.9-22.6
- Humidity (%): 44-56%
- Air changes (per hr): approximately 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 Oct 2007 To: 16 Nov 2007
Vehicle:
unchanged (no vehicle)
Controls:
other: not required: the untreated eye of the same animal served as control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 44.0 mg (range 36.9-47.7 mg) (corresponding to a volume of approximately 0.1 mL)
Duration of treatment / exposure:
single application without washing
Observation period (in vivo):
72 h
Reading time points: 1, 24, 48 and 72 h
Number of animals or in vitro replicates:
3 males
Details on study design:
SCORING SYSTEM: Draize scoring system

TOOL USED TO ASSESS SCORE: 2% fluorescein was instilled in the eyes immediately after the 24 h reading and the corneal epithelial damage assessed with a slit lamp
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
other: reversibility not applicable
Irritation parameter:
iris score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
2
Reversibility:
fully reversible within: 24 h
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0.67
Max. score:
3
Reversibility:
fully reversible within: 72 h
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
out of all 3 animals
Time point:
other: mean over 24, 48 and 72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 h
Irritant / corrosive response data:
Conjunctival redness (score 2) was observed in 3/3 animals 1 h after instillation. The redness persisted in 3/3 animals (score 1) until the 48 h reading time point. Chemosis (score 1-2) was observed in 3/3 animals and iridial irritation (score 1) was seen in 2/3 animals at the 1 h reading time point. Both effects had cleared completely by the 24 h reading. All effects were completely reversible within 72 h.
Remains of the test substance were noted in the treated eye of 3/3 animals on Day 1, while remains were present on the outside of the eyelids on Day 2 in 1/3 animals.
Other effects:
There was no mortality, no clinical signs were observed and the body weight was within the normal range during the study period.

Table 1: individual irritation scores

Rabbit #

 

Time

 

conjunctivae

 

iris

 

cornea

 

redness

chemosis

1

 

 

 

 

1 h1

2

1

1

0

24 h

1

0

0

0

48 h

1

0

0

0

72 h

0

0

0

0

Average*

0.67

0.0

0.0

0.0

2

 

 

 

 

1 h1

2

2

0

0

24 h2

1

0

0

0

48 h

1

0

0

0

72 h

0

0

0

0

Average*

0.67

0.0

0.0

0.0

3

 

 

 

 

1 h1

2

1

1

0

24 h

1

0

0

0

48 h

1

0

0

0

72 h

0

0

0

0

Average*

0.67

0.00

0.0

0.0

* mean of 24 + 48 + 72 h

1Remains of test substance in the eye

2Remains of the test substance on the outside of the eyelids

 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

To assess the skin irritation potential of 2-methyl-N-(4-sulfamoylphenyl) prop-2-enamide (SPM-N), a study was performed according to OECD Guideline 404 and under GLP conditions (Stitzinger, 2008c). 0.5 g test substance, moistened with 0.5 mL water, was applied to the clipped skin of New Zealand White rabbits under semi-occlusive conditions for 4 h. The scoring of skin reactions (erythema and edema) was performed 1, 24, 48 and 72 h after removal of the dressing. There were no skin irritation effects observed in any of the animals at any reading time point.

In the acute dermal toxicity study, SPM-N (in propylene glycol) at a dose of 2000 mg/kg bw was applied to the clipped skin of rats under occlusive conditions for 24 h (Stitzinger, 2008b). White staining of the skin was noted in all animals for up to 4 consecutive days in the period Day 2-5. Slight scales or scabs were seen in 1/5 males and 3/5 females for 1-10 consecutive days during Day 4-15, while focal erythema of grade 1 was observed in 2/5 females on Day 3 or 3-4, respectively. 

The skin irritation study, performed according to the standard test for the hazard assessment and classification (OECD Guideline 404 with 4 h exposure period under semi-occlusive conditions) did not result in skin irritation. The longer exposure period (24 h) employed in the acute dermal toxicity study shows that even under more rigorous conditions the test substance does not cause skin irritation that leads to a classification. Therefore, SPM-N is considered not to be a skin irritant.

Eye

The eye irritation potential of SPM-N was evaluated in a study performed according to OECD Guideline 405 and in compliance with GLP (Stitzinger, 2008d). An average of 44 mg (weight corresponds to 0.1 mL) was instilled into one eye each of 3 male New Zealand White rabbits. The other eye remained untreated and served as control. The eyes were examined and scored 1, 24, 48 and 72 h after the treatment. Remains of the test substance were noted in the treated eye of 3/3 animals on Day 1, while remains were present on the outside of the eyelids on Day 2 in 1/3 animals.

Chemosis (score 1-2) was observed in 3/3 animals and iridial irritation (score 1) was seen in 2/3 animals at the 1 h reading time point, but both had cleared completely by the 24 h reading time point. Conjunctival redness (score 2) was observed in 3/3 animals 1 h after instillation. The redness persisted in 3/3 animals until the 48 h reading time point, but was completely reversed by the following scoring time. The mean score for conjunctival redness after 24, 48, and 72 h was 0.67 for each of the 3 animals. The effects on cornea, iris and chemosis after 24, 48, and 72 h were scored 0 for all 3 animals. Based on the results of this study, SPM-N is considered not to be an eye irritant.


Justification for selection of skin irritation / corrosion endpoint:
There is only one study available.

Justification for selection of eye irritation endpoint:
There is only one study available.

Justification for classification or non-classification

The available data on skin and eye irritation of the test substance do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.