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Description of key information

For all the endpoints of the chapter 7.3, the name of the tested substance is DV-SOLV 1059.
The DV-SOLV 1059 is the previous name of the Rhodiasolv Polarclean. The specifications of the DV-SOLV 1059 are in line with the dossier and representative of the industrial product manufactured by Schirm.
The test item DV-SOLV 1089 was determined to be irritating to the eyes. It is not irritating to the skin.

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:
From 15 December 2009 to 11 March 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study to GLP
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: S&K-LAP K ft, Csaszar ut 135, Hungary
- Age at study initiation: approx. 14 weeks
- Weight at study initiation: 3706-4290 g
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 34 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17.0-20.6
- Humidity (%): 30-64
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 9 December 2009 To: 15 January 2010
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml
- Concentration (if solution): 100%
Duration of treatment / exposure:
4 hours
Observation period:
73 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure:
- % coverage: area approximately 6 cm2
- Type of wrap if used: gauze patch covered by plastic, truck encased in plastic and elastic tubing

REMOVAL OF TEST SUBSTANCE
- Washing (if done): water at body temperature
- Time after start of exposure: 4 hours

SCORING SYSTEM: according to Draize (1959)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Remarks on result:
other: no reaction
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24 h
Score:
0
Remarks on result:
other: no reaction
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Remarks on result:
other: no reaction
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 h
Score:
0
Remarks on result:
other: no reaction
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1 h
Score:
0
Remarks on result:
other: no reaction
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24 h
Score:
0
Remarks on result:
other: no reaction
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 48 h
Score:
0
Remarks on result:
other: no reaction
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 h
Score:
0
Remarks on result:
other: no reaction
Irritant / corrosive response data:
no reactions
Other effects:
none
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
DV-SOLV 1059 is not irritating to skin according to the criteria of this test.
Executive summary:

An acute skin irritation study was performed with DV-SOLV 1059 in New Zealand White rabbits. Parameters monitored during this study included mortality, body weight measurements and clinical observations. The irritancy of the test item was evaluated according to the Draize method (OECD No.: 404, 2002). The test item was administered undiluted, at a single dose of 0.5 ml. Gauze was placed onto the hairless skin of the rabbit, test item was applied to the gauze, additional gauze was placed over the test item and an adhesive clear plastic patch applied. The trunk was wrapped in clear plastic with medical tubing used to hold the patch in place. The untreated skin of each animal served as control. After 4 hours, the remaining test item was removed with water at body temperature. To assess skin irritation, animals were examined at 1, 24, 48 and 72 hours after the patch removal. Additional general examinations were performed daily. There was no mortality or systemic clinical changes related to DV-SOLV 1059 administration. There was no effect of treatment on body weight. At observation one, 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals. As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hours observation. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0.00, 0.00 and 0.00 respectively. According to Directive 2001/59/EC, DV-SOLV 1059 does not require classification as a skin irritant. According to the UN Globally Harmonised System of Classification and Labelling of Chemicals, DV-SOLV 1059 does not require classification as a skin irritant.

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:
04 May 2010 to 08 June 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study to GLP
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
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: S&K LAP Kft, 2173 Kartal, Csaszard ut 135, Hungary
- Age at study initiation:approx, 15 weeks
- Weight at study initiation: 3784-4615 g
- Housing: Individually in stainless steel cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: 33 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23
- Humidity (%): 24-62
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 03-Feb-2010 To: 22-Mar-2010
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL/animal
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
2 weeks
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
Washing (if done): no washing done


SCORING SYSTEM: according to the numerical scoring system listed in the Commission Regulation (EC) No 440/2008, B.5.
Data were summarized in tabular form, showing for each individual animal the irritation scores for the designated observation time, a description of the degree and nature of irritation, the presence of serious lesions and non-ocular effects. The scores of each animal at the following reading times (24, 48, 72 hours) were used in calculating the respective mean values (with the exception of the sclerae) for each type of lesion.


TOOL USED TO ASSESS SCORE: Varta Cliptrix diagnostic-lamp (Roth AG, 4153 Reinach / Switzerland)
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 2 weeks
Remarks on result:
other: individual mean scores: 1.0; 1.0; 1.0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72hours after instillation
Score:
0.33
Max. score:
2
Reversibility:
fully reversible within: 7 days
Remarks on result:
other: individual mean scores: 0.67; 0.33; 0.00
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
2.45
Max. score:
3
Reversibility:
fully reversible within: 2 weeks
Remarks on result:
other: individual mean scores: 3.00; 2.67; 1.67
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
0.78
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: individual mean scores: 0.33; 1.33; 0.67
Irritation parameter:
other: conjunctival discharge
Basis:
mean
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
2.22
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Remarks on result:
other: individual mean scores: 2.33, 2.33, 2.00
Irritant / corrosive response data:
The test item induced significant irritation but no irreversible damage to the rabbit eye.
Other effects:
None

Individual Scores of eye irritation

 

Abbreviations:

R:     Redness CH:      Chemosis         D:        Discharge         OD:     Opacity degree of density

OE:   Extension of opaque area IPR:     Initial pain reaction        -:         No data

 

Time

Animal No.

Score of Irritation

IPR

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

1 hour

00532

2

3

3

1

4

0

0

-

2

00530

2

3

3

1

4

0

0

-

2

00533

2

3

3

0

0

0

0

-

2

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

24 hours

00532

3

1

3

1

4

0

0

-

00530

3

2

3

1

4

0

0

-

00533

2

2

2

1

4

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

48 hours

00532

3

0

3

1

3

1

0

-

00530

3

2

3

1

4

1

0

-

00533

2

0

3

1

3

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

72 hours

00532

3

0

1

1

2

1

0

-

00530

2

0

1

1

4

0

0

-

00533

1

0

1

1

1

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

1 week

00532

1

0

0

0

0

0

0

-

00530

1

0

0

1

2

0

0

-

00533

0

0

0

0

0

0

0

-

 

Time

Animal No.

Score of Irritation

Conjunctivae

Corneal opacity

Iris

Control eye

Other sign

R

CH

D

OD

OE

R

2 weeks

00532

0

0

0

0

0

0

0

-

00530

0

0

0

0

0

0

0

-

00533

0

0

0

0

0

0

0

-

 

Mean values of ocular irritation (24, 48, 72 hour readings)

 

Animal number

Sex

Corneal opacity

Iris

Conjunctivae

Redness

Chemosis

Discharge

00532

M

1.00

0.67

3.00

0.33

2.33

00530

M

1.00

0.33

2.67

1.33

2.33

00533

M

1.00

0.00

1.67

0.67

2.00

 

Interpretation of results:
irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria (Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labeling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and
amending Regulation (EC) No 1907/2006), DV-SOLV 1059 is considered to be “irritating” to the rabbit eye.
Executive summary:

An acute eye irritation study of the test item DV-SOLV 1059 was performed in New Zealand White rabbits. The irritation effects of the test item were evaluated according to the Draize method (OECD No.: 405, 2002). The test item was placed into the conjunctival sac of the left eye of each animal. The untreated right eye served as control. A volume of 0.1 mL of the test item was administered as a single dose. The eyes were examined at 1, 24, 48, 72 hours and 1 and 2 weeks after the application.

Initial Pain Reaction() (score 2) was observed in all animals.

One hour after the application, conjunctival redness (score 2) was observed in all animals, conjunctival chemosis (score 3) was noted in all animals, conjunctival discharge (score 3) was seen in all animals and corneal opacity (score 1, extension 4) was observed in two animals.

At 24 hours after treatment,conjunctival redness (score 3) was observed in two animals, conjunctival redness (score 2) in one animal, conjunctival chemosis (score 1) was observed in one animal, conjunctival chemosis (score 2) was seen in two animals, conjunctival discharge (score 3) was noted in two animals, conjunctival discharge (score 2) in one animal and corneal opacity (score 1, extension 4) was seen in all animals.

At 48 hours after treatmentconjunctival redness (score 3) was observed in two animals, conjunctival redness (score 2) was seen in one animal, conjunctival chemosis (score 2) was seen in one animal, conjunctival discharge (score 3) was observed in all animals, corneal opacity (score 1, extension 4) was noted in one animal and corneal opacity (score 1, extension 3) was observed in two animals. The iris was injected (score 1) in two animals.

At 72 hours after treatmentconjunctival redness (score 3) was observed in one animal, redness (score 2) was noted in one rabbit, redness (score 1) was seen one animal, conjunctival discharge (score 1) was found in all rabbits, corneal opacity (score 1, extension 4) was observed in one animal, corneal opacity (score 1, extension 2) was noted in one rabbit and corneal opacity (score 1, extension 1) was seen one rabbit. The iris was injected (score 1) in one animal.

At 1 week after treatmentconjunctival redness (score 1) was found in two animals and corneal opacity (score 1, extension 2) was observed in one rabbit.

At 2 weeks after treatmentthere were no clinical signs observed. As there were no clinical signs observed, the study was terminated. During the study, the control eye of each animal was symptom-free. The general state and behaviour of animals were normal throughout the study period. There were no notable body weight changes during the study period.

The test item DV-SOLV 1059, applied to the rabbits eye mucosa, caused significant conjunctival irritant effects at one hour which were not reduced at 48 hours after application. The effects were full reversible within 2 weeks. According to Regulation (EC) No 1272/2008, DV-SOLV 1059 requires classification as an eye irritant(Category 2; Reversible effects on the eye/irritating to eyes).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

On study of reliability 1 according to Klimisch cotation critera, is available for dermal route (Leyshon A., 2010) and was selected as a key study. In this study (OECD 404), 3 New Zealand White rabbits were treated by a topical semi-occlusive application of 0.5 mL of undiluted DV-SOLV 1059 for 4 hours and were observed 1, 24, 48 and 72 hours after exposure.

There was no mortality or systemic clinical changes related to DV-SOLV 1059 administration. There was no effect of treatment on body weight. At observation one, 24, 48 and 72 hours after patch removal, there were no observed clinical signs noted on the skin of the treated animals. As no clinical signs were observed up to 72 hours after patch removal, the study was terminated after the 72 hours observation. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were0.00,0.00 and0.00respectively.

Based upon the referred classification criteria (commission Directive 2001/59/EC of August 2001 and UN Globally Harmonised System of Classification and Labelling of Chemicals), DV-SOLV 1059 is considered to be "not irritating" to rabbit skin.

 Eye irritation:

Two studies of reliability 1 according to Klimisch cotation critera are available to evaluate the eye irritating potential of the test substance: onein vitrostudy (Warren N., 2010) followed by onein vivostudy (Esdaile DJ., 2010). In thein vitrostudy (Bovine Corneal opacity and Permeability Assay, OECD 437), the undiluted test material was applied for 10 minutes followed by an incubation period of 120 minutes. Negative and positive control materials were tested concurrently. The two endpoints, decreased light transmission through the cornea (opacity) and increased passage of sodium fluorescein dye through the cornea (permeability), were combined in an empirically derived formula to generate anIn VitroIrritancy Score. A test material that induces anIn VitroIrritancy Score ≥55.1 is defined as an ocular corrosive or severe irritant.The scores were: DV-SOLV 1059: 25.3, negative control: 0.4; positive control: 44.3.

The test material DV-SOLV 1059 was considered not to be an ocular corrosive or severe irritant.

In order to know if the test substance is irritant to eyes or not, the BCOP assay was followed by an in vivo OECD 405 study. In this study,3 New Zealand White rabbits were treated by an ocular instillation of 0.1 mL of undilutedDV-SOLV 1059and were observed 1, 24, 48 and 72 hoursand 1 and 2 weeks after the application.The test item DV-SOLV 1059 caused significant conjunctival irritant effects at one hour which were not reduced at 48 hours after application. The effects were full reversible within 2 weeks.

According to Regulation (EC) No 1272/2008, DV-SOLV 1059 requires classification as an eye irritant( Category 2; Reversible effects on the eye/irritating to eyes).

Justification for selection of skin irritation / corrosion endpoint:
only one study available (GLP and OECD guideline 404 compliant)

Justification for selection of eye irritation endpoint:
only one study available (GLP and OECD guideline 405 compliant)

Effects on eye irritation: irritating

Justification for classification or non-classification

The substance is classified as an eye irritant (Xi; R36 or Eye irrit. 2, H319 according to Directive 67/548/EEC or Regulation (EC) 1272/2008, respectively) because significant conjunctival irritant effects were still observed 48 hours after application but were full reversible within 2 weeks.

The substance does not fulfill the criteria for classification as "irritating to skin" according to Regulation (EC) No 1272/2008 because no local effects were observed 24, 48 and 72 hours after application.