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Administrative data

Description of key information

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:
23/11/2000-26/112000
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented report of a guideline study conducted to GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Elevage Cunicole de Val de Selle (80160 Prouzel, France)
- Weight at study initiation: 2.6 +/- 0.1 kg
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (Total quantity applied): 0.5 mL
- Administration frequency: once

TEST MATERIAL
- Amount applied : 0.5 mL


Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after the patch removal.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: right flank

REMOVAL OF TEST SUBSTANCE
- Washing : no

SCORING SYSTEM: Draize's score
Irritation parameter:
overall irritation score
Remarks:
Draize's score
Basis:
mean
Time point:
other: 1, 24, 48 and 72 hours after the patch removal
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 3 days for 2 animals and 6 days for one animal
Irritant / corrosive response data:
Neither erythema nor oedema were noted in any animals at any examination time.
Other effects:
No other cutaneous reactions were noted.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
ADAMQUAT MC 80 is not irritating to rabbit skin.
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:
Start of the experimental phase June 10, 2014; Termination of the in-life phase June 28, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented GLP guideline study on a well characterized test material.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Manfred Bauer Kaninchen, Lohe 7/1, 74632 Neuenstein,Germany
- Age at study initiation: Approx. 7.5 - 8.5 months
- Weight at study initiation: 4.2 - 4.8 kg
- Housing: For 8 hours following test item application, the animals were kept singly in restrainers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excrements and urine.
During the acclimatisation period and after the 8-hour period in restrainers, the animals were kept singly in cages with dimensions of 380 mm x 425 mm x 600 mm (manufacturer: Dipl.Ing. W. EHRET GmbH, 16352 Schönwalde, Germany)
- Diet (e.g. ad libitum): The food was available ad libitum before and after the exposure period.
- Water (e.g. ad libitum): Tap water was offered daily ad libitum.
- Acclimation period: At least 20 adaptation days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C (maximum range).
- Humidity (%): The relative humidity amounted to 30% - 70% (maximum range).
- Air changes (per hr): 15 to 20 times
- Photoperiod (hrs dark / hrs light): Rooms were lit (150 lux at approx 1.5 m room height) and darkened on a 12-hour light/12-hour dark cycle.


IN-LIFE DATES: From: June 01, 2014 To: June 28, 2014
Vehicle:
unchanged (no vehicle)
Controls:
other: The left eye, which remained untreated, served as a control.
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL of the test item were administered into one eye. The test item was placed into the conjunctival sac of the right eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second in order to prevent loss of the material. The left eye, which remained untreated, served as a control.
- Concentration (if solution):


VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of treatment / exposure:
The test was performed initially using one animal. As no corrosive or severe irritant effects were observed in this animal, 2 further animals were employed 24 hours after start of the initial test.
Observation period (in vivo):
The eyes were examined ophthalmoscopically with a slit lamp prior to the administration and 1, 24, 48, 72 hours and 4 to 9 days after the administration. The eye reactions were observed and registered.
Number of animals or in vitro replicates:
3 female animals
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:


SCORING SYSTEM:
CORNEA
Opacity degree of density (area most dense taken for reading)
no ulceration or opacity 0
scattered or diffuse areas of opacity (other than slight dulling of normal lustre), details of iris clearly visible 1
easily discernible translucent area, details of iris slightly obscured 2
nacreous areas, no details of iris visible, size of pupil barely discernible 3
opaque cornea, iris not discernible through the opacity 4


IRIS
normal 0
markedly deepened rugae, congestion, swelling, moderate circumcorneal hyperaemia, or injection, iris reactive to light (a sluggish reaction is considered to be an effect) 1
haemorrhage, gross destruction, or no reaction to light 2


CONJUNCTIVAE
Redness (refers to palpebral and bulbar conjunctivae, excluding cornea and iris)
normal 0
some blood vessels hyperaemic (injected) 1
diffuse, crimson colour; individual vessels not easily discernible 2
diffuse beefy red 3

CHEMOSIS
Swelling: refers to lids and/or nictitating membranes
normal 0
some swelling above normal 1
obvious swelling with partial eversion of lid 2
swelling with lids about half-closed 3
swelling with lids more than half-closed 4



TOOL USED TO ASSESS SCORE: hand-slit lamp / biomicroscope / fluorescein
One day before and 24 hours after administration, fluorescein was applied to the eyes before being examined to aid evaluation of the cornea for possible lesions. The fluorescein test was repeated on each day of observation. (Fluorescein SE Thilo drops (ALCON PHARMA GmbH, 79108 Freiburg, Germany))
Fluorescein-Test:

DEGREE OF STAINING
no staining 0
scattered or diffuse colouration, details of iris clearly visible 1
easily discernible translucent area, details of iris slightly obscured 2
opalescent areas, details of iris not discernible, extent of pupil difficultly determinable 3
opaque cornea, iris not discernible through the opacity 4
INVOLVED AREA OF CORNEA
none 0
up to 1/4 of the surface 1
1/4 to 1/2 of the surface 2
1/2 to 3/4 of the surface 3
3/4 to whole surface. 4

Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritation parameter:
iris score
Basis:
animal #1
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritation parameter:
iris score
Basis:
animal #2
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritation parameter:
iris score
Basis:
animal #3
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
other: 24h, 48h, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 4 days
Remarks on result:
other: Mean score
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
other: 24h, 48h, 72h
Score:
1.67
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: Mean score
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
other: 24h, 48h, 72h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 6 days
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
other: 24h, 48h, 72h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 8 days
Remarks on result:
other: Mean score
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
other: 24h, 48h, 72h
Score:
0
Max. score:
0
Reversibility:
other: No effect
Irritant / corrosive response data:
The irises were not affected by instillation of the test item.

Other effects:
There were no systemic intolerance reactions.

Acute eye irritation/corrosion test of Flocryl™ ADAM / MC80 in  rabbits

TABLE 1 Examination of the treated eye

Time after administration

CORNEA

IRIS

CONJUCTIVAE

Fluorescein Test

 

Opacity

 

Redness*

Chemosis**

Grade

Area

 

Animal Number : 1 / 2 / 3

right eye: 0.1 mL Test item/animal

 

 

 

 

before dosing

0/0/0

0/0/0

0/0/0

0/0/0

-/-/-

-/-/-

60 minutes

0/0/0

0/0/0

1/1/2

0/0/0

-/-/-

-/-/-

24 hours

0/0/0

0/0/0

1/1/1

0/3/0

0/2/1

0/1/1

48 hours

0/0/0

0/0/0

1/2/1

0/2/0

0/1/1

0/1/1

72 hours

0/0/0

0/0/0

1/2/1

0/2/0

0/1/1

0/1/1

4 days

0/0/0

0/0/0

0/2/2

0/1/1

0/0/0

0/0/0

5 days

-/0/0

-/0/0

-/2/2

-/1/1

-/0/0

-/0/0

6 days

-/0/0

-/0/0

-/2/1

-/1/0

-/0/0

-/0/0

7 days

-/0/0

-/0/0

-/1/0

-/1/0

-/0/0

-/0/0

8 days

-/0/-

-/0/-

-/0/-

-/1/-

-/0/-

-/0/-

9 days

-/0/-

-/0/-

-/0/-

-/0/-

-/0/-

-/0/-

* refers to palpebral and bulbar conjunctivae; excluding cornea and iris

* swelling: refers to lids and/or nictitating membrane

 

 

 

- no examination

 

 

 

 

 

 

 

 
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to the EC-Commission directive 67/548/EEC and its subsequent amendments on the approximation of the laws, regulations and administrative provision relating to the classification, packaging and labelling of dangerous substances and the results obtained under the present test conditions FlocrylTM ADAM / MC80 was non - irritating to eyes, hence, no labelling is required.
Also, according to the Globally Harmonized System (GHS) and EC-Regulation 1272/2008 and subsequent regulations, the test item is non-irritating to eyes; classification and labelling of the substance is not necessary.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

The substance was non-irritating to skin in a GLP guideline study (Manciaux, 2002).

A study dating from 1985 by Collier demonstrated eye irritation. However, an in-depth review of the study report revealed several major problems with the study. Furthermore, the test susbstance was not identified and considering the test period, was most probably not a production sample. For these reasons, a new, GLP study has been conducted on a sample with exactly the same substance identity as the registration. This study demonstrated that there was a complete absence of eye irritation.

Justification for classification or non-classification

Substance was non-irritating to skin and eyes in GLP guideline studies.