Registration Dossier

Administrative data

Description of key information

The skin irritation/corrosion studies revealed that Atmer 163 is corrosive to the skin of rabbits. 

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
Open application, 72 h observation is missing
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ranch Rabbits, Crawley Down, Sussex, UK
- Weight at study initiation: 2.5-3.0 kg
- Housing:In satinised aluminium steel cages (605 mm width x 490 mm depth x 455 mm height) with one animal per cage
- Diet: Ad libitum
- Water: Ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-20
- Humidity (%): 50-60

Type of coverage:
open
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 100%


Duration of treatment / exposure:
3 minutes
Observation period:
Immediately after washing and 2, 24, 48 and 96 h after treatment
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: Whole flank

REMOVAL OF TEST SUBSTANCE
- Washing (if done): By gentle swabbing with cotton wool soaked in lukewarm water
- Time after start of exposure: 3min

SCORING SYSTEM: Draize
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: average 24 and 48h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 96h
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: average 24 and 48h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 96h
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: average 24 and 48h
Score:
3.5
Max. score:
4
Reversibility:
not fully reversible within: 96h
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
other: average 24 and 48h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 96h
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
other: average 24 and 48h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 96h
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
other: average 24 and 48h
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 96h
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: average 24 and 48h
Score:
3.5
Max. score:
4
Reversibility:
fully reversible within: 96h
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: average 24 and 48h
Score:
4
Max. score:
4
Reversibility:
fully reversible within: 96h
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: average 24 and 48h
Score:
3.5
Max. score:
4
Reversibility:
fully reversible within: 96h
Irritation parameter:
edema score
Basis:
animal #4
Time point:
other: average 24 and 48h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 96h
Irritation parameter:
edema score
Basis:
animal #5
Time point:
other: average 24 and 48h
Score:
3
Max. score:
4
Reversibility:
fully reversible within: 96h
Irritation parameter:
edema score
Basis:
animal #6
Time point:
other: average 24 and 48h
Score:
3.5
Max. score:
4
Reversibility:
fully reversible within: 96h
Irritant / corrosive response data:
All animals showed signs of necrosis nintety-six hours after application; these included, typically, thickening of the skin at the application site, eschar formation and blanching and one animal had darkened skin at the appliction site (see table 2).

Table 1: Corrosive reactions

Number of animals with corrosion/all tested animals after

3min

24h

48h

0/6

0/6

1/6

Table 2: Skin corrosion parameters

 

Thickened skin after

Blanched skin after

Hardened skin after

Darkened skin after

Animal number

24h

48h

96h

24h

48h

96h

24h

48h

96h

24h

48h

96h

1

-

-

+

-

-

-

-

-

-

-

-

-

2

-

-

+

-

-

-

-

-

-

-

-

-

3

-

+

+

-

-

-

-

+

+

-

+

+

4

-

+

+

-

-

-

-

-

-

-

-

-

5

-

+

+

-

-

+

-

-

-

-

-

-

6

-

+

+

-

-

-

-

-

-

-

-

-

 

Cracked skin after

Wrinkled skin after

Eschar formation after

Animal number

24h

48h

96h

24h

48h

96h

24h

48h

96h

1

-

-

-

-

-

-

-

-

-

2

-

-

-

-

-

-

-

-

-

3

-

-

-

-

-

-

-

+

+

4

-

-

-

-

-

-

-

-

-

5

-

-

-

-

+

-

-

-

-

6

-

-

-

-

-

-

-

-

-

Interpretation of results:
Category 1B (corrosive) based on GHS criteria
Conclusions:
Undiluted Synprolam 35x2 when administered to rabbit skin for 3 min is corrosive to one out of 6 animals after 48h observation time and 6 out of 6 animals after 96 h observation time and therefore is classified:
CLP: Category 1B, H314 (causes severe skin burns)
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A skin irritation study similar to OECD guideline 404 was performed with white rabbits (CTL-T-1522). 6 animals were treated with 0.5 mL of the undiluted test substance for 3 minutes by an open application to the skin. The reactions were observed immediately after washing and 2, 24, 48 and 96 hours after treatment. All animals showed signs of necrosis ninety-six hours after application; these included, typically, thickening of the skin at the application site, eschar formation and blanching and one animal had darkened skin at the application site. None of the animals died or showed any systemic effects. Undiluted test substance when administered to rabbit skin for 3 minutes is corrosive to one out of 6 animals after 48 hours observation time and 6 out of 6 animals after 96 hours observation time and has therefore to be classified.

A further skin irritation study similar to OECD guideline 404 was performed with white rabbits (CTL/T/1357). The skin of 6 animals was treated with the undiluted test substance for 4 hours. The way of dermal application was not specified. The reactions were observed after 4, 24 and 48 hours. After 4 hours no reactions had been reported. Five out of six rabbits had visible signs of necrosis at the 24 hour observation, after 48 hours all animals were showing signs of necrosis. None of the animals died or showed any systemic effects. Undiluted test substance when administered to rabbit skin for 4 hours is corrosive to 6 out of 6 animals after 48 hours observation time and has therefore to be classified.  

According to REGULATION (EC) No 1907/2006 Annex VIII 8.2.1 column 2 an eye irritation study does not need to be conducted if the substance is classified as corrosive to the skin.


Justification for classification or non-classification

3 minutes dermal exposure of Atmer 163 to rabbit skin resulted in corrosive effects. 1 out of 6 animals after 48 hours and 6 out of animals after 96 hours showed corrosion of the skin. Additionally the supporting study revealed necrosis in all treated animals after a 4 hour dermal application. According to CLP (1272/2008/EC), Atmer 163 has to be classified as:

CLP: Category 1B, H314 (causes severe skin burns)