Registration Dossier

Administrative data

Description of key information

Reliable data on skin corrosion and skin irritation is available. Both the vitro skin corrosion test and the vivo skin irritation study did not show significant irritating properties for GABEPRO® GPM-800.
A reliable in vivo eye irritation in rabbit is available, demonstrating no significant eye irritating properties for DPM 3 -800LC.

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:
07 July 2015 - 18 July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Version / remarks:
(2002)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Version / remarks:
(1998)
Deviations:
no
Qualifier:
according to guideline
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 test system and environmental conditions:
- Source: Charles River France, L’Arbresle Cedex, France
- Age at study initiation: 15-16 weeks
- Weight at study initiation: 3109-3281 g
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad, Italy). Hay and wooden sticks were abailable during the study period.
- Water: Free access to tap water.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
Deviations from the maximum level of daily mean relative humidity occurred. As laboratory historical data did not indicate an effect of these deviations, the study integrity was not adversely affected by the deviations.
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 07 July 2015 to 18 July 2015
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
other: Adjacent areas of the untreated skin of each animal served as controls.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
Single application
Observation period:
7 days
Number of animals:
3 males
Details on study design:
STUDY DESIGN
The study was performed in a stepwise manner and was started by treatment of a single rabbit (sentinel). The two other animals were treated in a similar manner one week later, after considering the degree of skin irritation observed in the first animal.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

TREATMENT
The test substance was applied to the skin of one flank, using a metalline patch of 2x3 cm. The patch was mounted on Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water and watery ethanol (50% v/v).

OBSERVATIONS
- Mortality/Viability: Twice daily
- Toxicity: At least once daily
- Body Weight: Day of treatment (prior to application) and after the final observation
- Necropsy: Not performed
- Irritation: The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and/or 7 days after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM
The irritation was assessed according to the numerical scoring system according to OECD 404.
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
(sentinel)
Time point:
other: 24, 48 and 72 hours (mean)
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 hours (mean)
Score:
0.7
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 hours (mean)
Score:
0.3
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
edema score
Basis:
animal: #1 (sentinel), #2 and #3
Time point:
other: 24, 48 and 72 hours (mean)
Score:
0
Max. score:
4
Irritant / corrosive response data:
Four hours exposure to 0.5 mL of GABEPRO® GPM-800 resulted in very slight erythema and very slight oedema in the treated skin areas of the three rabbits. The skin irritation resolved within 7 days after exposure in the first animal, within 72 hours in the second animal and within 48 hours in the remaining animal. There was no evidence of a corrosive effect on the skin.
Other effects:
- Remnants of the test substance were present on the skin of all animals on Days 1 and 2
- No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred

 

 Animal

930 (sentinel)

936

935

Time after exposure

Erythema

(0-4)

Oedema

(0-4)

comments

Erythema

(0-4)

Oedema

(0-4)

comments

Erythema

(0-4)

Oedema

(0-4)

comments

   1 hour

1

1

b

1

1

b

1

1

b

 

 24 hours

1

0

c

1

0

c

1

0

c

 

 48 hours

1

0

r

1

0

-

0

0

-

 

 72 hours

1

0

r

0

0

-

0

0

-

 

   7 days

0

0

-

 

 

 

 

 

 

 

 

comments:

b.     Sticky remnants of the test substance present.

c.     Dry remnants of the test substance present.

r.      Scattered erythema.

Interpretation of results:
other: not classified according to Regulation (EC) No 1272/2008
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on the results obtained in a skin irritation study with rabbits, performed according to OECD/EC test guidelines, GABEPRO® GPM-800 does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.
Executive summary:

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 (2002) and according to GLP principles, 3 male rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of GABEPRO® GPM-800. Exposure resulted in very slight erythema and very slight oedema in the treated skin areas of the three rabbits. The skin irritation resolved within 7 days after exposure in the first animal, within 72 hours in the second animal and within 48 hours in the remaining animal. No signs of toxicity nor mortalities were observed. Based on the result of this study, GABEPRO® GPM-800 does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.

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:
December 1969
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
The study meets the EC Standards (conducted equivalent to OECD 405). Non GLP.
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
yes
Remarks:
no details on test animals and environmental conditions, animals were not observed for irritation 48 hours after exposure: not expected to affect the outcome of the study
Principles of method if other than guideline:
Methods for the Study of Irritation and Toxicity of Substances Applied Topically to the Skin and Mucous Membranes", Draize, John H., Woodard, Geoffrey, and Calvery, Herbert O., J. Pharm. & Exp. Ther., 82, 4, December 1944.
GLP compliance:
no
Remarks:
not present at the time of performance.
Species:
rabbit
Strain:
other: New Zealand albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
No data

ENVIRONMENTAL CONDITIONS
No data
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye of each animal served as a scoring control.
Amount / concentration applied:
TEST MATERIAL
- Amoun applied: 0.1 mL
Duration of treatment / exposure:
Single instillation on Day 1.
Observation period (in vivo):
The eyes of each animal were examined approximately 1 minute, 1, 24 and 72 hours and 7 days after instillation of the test substance.
Number of animals or in vitro replicates:
5
Details on study design:
STUDY DESIGN:
The undiluted test material was instilled into the conjunctival sac of the right eye of each test rabbit.

OBSERVATIONS:
The eyes of each animal were examined approximately 1 minute, 1, 24 and 72 hours and 7 days after instillation of the test substance.

SCORING SYSTEM:
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to OECD 405.
Remarks on result:
not measured/tested
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
animal #1, #2, #3, #4 and #5
Time point:
other: 24 and 72 hrs
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Remarks:
animal #1, #2, #3, #4 and #5
Time point:
other: 24 and 72 hrs
Score:
0.5
Max. score:
2
Reversibility:
fully reversible within: 72 hrs.
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
mean
Remarks:
animal #1, #2, #3, #4 and #5
Time point:
other: 24 and 72 hrs
Score:
0.5
Max. score:
3
Reversibility:
fully reversible within: 72 hrs.
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 and 72 hrs
Score:
0
Max. score:
4
Irritant / corrosive response data:
Iridal and conjunctival irritation were noted one minute after instillation. Within 72 hours, the ocular tissues had returned to normal.
Interpretation of results:
other: not classified according to Regulation (EC) No 1272/2008
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an eye irritation study with rabbits, performed equivalent to OECD 405 test guideline, slight iridal and conjunctival irritation was observed. Within 72 hours, the ocular tissues had returned to normal.
Executive summary:

The test substance DPM 3 -800LC was tested in an eye irritation study with rabbits, performed equivalent to OECD 405 test guideline.

Iridal and conjunctival irritation were noted one minute after instillation. Within 72 hours, the ocular tissues had returned to normal.

Based on the results, the substance DPM 3 -800LC does not have to be classified for eye irritation according to Regulation (EC) No 1272/2008.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

skin

In an in vitro skin corrosion test using a human three dimensional epidermal model (EpiDerm (EPI-200)), conducted according to OECD 431 and GLP principles, the possible corrosive potential of GABEPRO® GPM-800 was tested through topical application for 3 minutes and 1 hour.Reliable negative and positive controls were included. Fifty μL of the substance was applied directly on top of the skin tissue. Skin corrosion is expressed as the remaining cell viability after exposure to the test substance. The relative mean tissue viability obtained after 3-minute and 1-hour treatments with the substance compared to the negative control tissues was 57% and 24%, respectively. Because the mean relative tissue viability was not below 50% after the 3-minute treatment and not below 15% after the 1-hour treatment, GABEPRO® GPM-800 is considered to be not corrosive to skin.

In an in vitro skin irritation test using a human skin model (EPISKIN Small Model), conducted according to OECD 439 and GLP principles, the influence of GABEPRO® GPM-800 on the viability of human skin was tested. Reliable negative and positive controls were included.

The relative mean tissue viability obtained after 15 minutes treatment with GABEPRO® GPM-800 compared to the negative control tissues could not be determined due to a high non-specific MTT reduction. Therefore it is concluded that GABEPRO® GPM-800 cannot be tested in the in vitro skin irritation test, due to its interaction with MTT.

In an in vivo skin irritation study in rabbits, conducted in accordance with OECD 404 (2002) and according to GLP principles, 3 male rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of GABEPRO® GPM-800. Exposure resulted in very slight erythema and very slight oedema in the treated skin areas of the three rabbits. The skin irritation resolved within 7 days after exposure in the first animal, within 72 hours in the second animal and within 48 hours in the remaining animal. No signs of toxicity nor mortalities were observed. Based on the result of this study, GABEPRO® GPM-800 does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.

eye

The test substance DPM 3 -800LC was tested in an eye irritation study with rabbits, performed equivalent to OECD 405 test guideline.

Iridal and conjunctival irritation were noted one minute after instillation. Within 72 hours, the ocular tissues had returned to normal.

Based on the results, the substance DPM 3 -800LC does not have to be classified for eye irritation according to Regulation (EC) No 1272/2008.


Justification for selection of skin irritation / corrosion endpoint:
Reliable skin irritation/corrosion study in rabbit according to OECD 404 and in accordance with GLP principles (in vitro corrosion test was negative, in vitro irritation test was not suitable, due to interaction of the substance with MTT)

Justification for selection of eye irritation endpoint:
Reliable eye irritation/corrosion study in rabbit equivalent to OECD 405.

Justification for classification or non-classification

In reliable in vitro en in vivo corrosive/ irritation studies, no significant adverse effects were observed. Based on the results of these studies, GABEPRO® GPM-800 does not need to be classified for skin irritation/corrosion in accordance with Regulation (EC) No 1272/2008 on Classification, Labelling and Packaging of Substances and Mixtures.