Registration Dossier

Administrative data

Description of key information

Two in vitro studies for skin corrosion/irritation and one in vivo reliable study in rabbits showed no signs of skin irritation.
One in vitro study and one in vivo study in rabbits showed no signs of irritation to the eyes.

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 the 01-Jul-2009 to 05-Oct-2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study has been performed according to OECD guidelines and EC methods in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [SR 813.112.1]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26th, 1997 by decision of the OECD Council [C(97)186/Final]. These principles are compatible with Good Laboratory Practice regulations specified by regulatory authorities throughout the European Community, the United States (EPA and FDA), and Japan (MHLW, MAFF and METI). The study was conducted in compliance with agreed protocols, with no deviations from standard test guidelines.
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan France ZI Le Malcourlet 03800 Gannat / France
- Age at study initiation: males: 15 weeks, females 15 weeks
- Weight at study initiation: male: 2245 g, females 2393 g and 2546 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (Harlan Laboratories Ltd., Füllinsdorf) and haysticks 4642 (batch no. 69/08, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 27/09) provided by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland.
- Water (e.g. ad libitum):Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 01-Jul-2009 to 05-Jul-2009


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 06-Jul-2009 To: 10-Jul-2009
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped with an electric clipper
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/animal

Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
1 male, 2 females
Details on study design:
TEST SITE
- Area of exposure: approx. 6.25 cm2
- % coverage: approximately 0.4% of the surface area
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restrainer bandage wrapped around the abdomen


REMOVAL OF TEST SUBSTANCE
- Washing (if done): after the dressing was removed the skin was flushed with lukewarm tap water to clean the application site
- Time after start of exposure: 4hours


SCORING SYSTEM: according to the numerical scoring system listed in the Commission Regulation (EC) No. 440/2008, B.4, at approximately 1, 24, 48 and 72 hours after exposure (removal of the dressing, gauze patch and test item).
Data were summarized in tabular form, showing for each individual animal the irritation scores for erythema and oedema at all measurement intervals. Any lesions were described, including the degree and nature of irritation, corrosion or any other toxic effects observed, and their reversibility.
The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. An animal is positive when the mean score is 2 or greater. The test is positive for irritation when at least 2 animals are positive for the same endpoint (erythema/eschar or oedema).
Irritation parameter:
erythema score
Basis:
other: mean score for animal numbers 19, 20 and 21
Time point:
other: mean value of scores at 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: no skin reaction
Remarks on result:
other: individual mean scores: 0 -0 -0
Irritation parameter:
edema score
Basis:
other: mean score for animal numbers 19, 20 and 21
Time point:
other: mean value of scores at 24, 48 and 72 hours after treatment
Score:
0
Max. score:
4
Reversibility:
other: no skin reaction
Remarks on result:
other: individual mean scores: 0 - 0 - 0
Irritant / corrosive response data:
The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.
Other effects:
No staining produced by the test item of the treated skin was observed.
Neither were alterations of the treated skin observed nor were corrosive effects evident on the skin.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based upon the referred classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008, TRIQUAT Monomer is considered to be “not irritating” to rabbit skin.
Executive summary:

The primary skin irritation potential of TRIQUAT Monomer was investigated according to OECD test guideline No. 404, Commission Regulation (EC) No. 440/2008, B.4. and Regulation (EC) No 1272/2008. The test item was applied by topical semi-occlusive application of 0.5 mL to the intact left flank of each of three young adult New Zealand White rabbits. The duration of treatment was four hours. The scoring of skin reactions was performed 1, 24, 48 and 72 hours after removal of the dressing.

The test item did not elicit any skin reactions at the application site of any animal at any of the observation times (all scores 0). The individual mean score for erythema/eschar and oedema for each of the three animals was therefore 0.

The test item did not cause any staining of the treated skin. No corrosive effects were noted on the treated skin of any animal at any of the measuring intervals and no clinical signs were observed.

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:
10-Jul-2009 to 20-Jul-2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study has been performed in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [SR 813.112.1]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26th, 1997 by decision of the OECD Council [C(97)186/Final]. These principles are compatible with Good Laboratory Practice regulations specified by regulatory authorities throughout the European Community, the United States (EPA and FDA), and Japan (MHLW, MAFF and METI).
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan France ZI Le Malcourlet 03800 Gannat / France
- Age at study initiation: males: 16 weeks, females 16 weeks
- Weight at study initiation: male: 2327 g, females 2509 and 2725 g
- Housing: Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks (Harlan Laboratories Ltd., Füllinsdorf) and haysticks 4642 (batch no. 69/08, Provimi Kliba AG) were provided for gnawing.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 27/09) provided by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland.
- Water (e.g. ad libitum):Community tap water from Füllinsdorf ad libitum.
- Acclimation period: 10-Jul-2009 to 14-Jul-2009


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark


IN-LIFE DATES: From: 15-Jul-2009 To: 20-Jul-2009
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):
72 hours
Number of animals or in vitro replicates:
1 male
2 females
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:
other: mean cores for animal numbers 84, 85 and 86
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
0
Max. score:
4
Reversibility:
other: No effects observed
Remarks on result:
other: individual mean score: 0 -0 -0
Irritation parameter:
iris score
Basis:
other: mean scores for animal numbers 84, 85 and 86
Time point:
other: mean value of scores at 24, 48 and 72hours after instillation
Score:
0
Max. score:
2
Reversibility:
other: no effects observed
Remarks on result:
other: individual mean scores: 0 - 0 -0
Irritation parameter:
conjunctivae score
Basis:
other: mean scores for animal numbers 84, 85 and 86
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
0
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: individual mean scores: 0 - 0 -0
Irritation parameter:
chemosis score
Basis:
other: mean scores for animal numbers 84, 85 and 86
Time point:
other: mean value of scores at 24, 48 and 72 hours after instillation
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: individual mean scores: 0 - 0 -0
Irritant / corrosive response data:
The test item did not induce significant or irreversible damage to the rabbit eye.
Other effects:
No staining produced by the test item of the treated eye was observed.
Slight scleral reddening noted in the male and one female at the 1-hour reading. The slight scleral reddening persisted up to the 24- (the male) or
the 48-hour reading (one female).
The instillation of TRIQUAT Monomer into the eye resulted in mild, early-onset and transient ocular changes, such as conjunctival and scleral reddening as well as conjunctival chemosis in the male and one female. The conjunctival effects were no longer evident from 24 hours after treatment. The scleral reddening persisted in both animals at the 24 hours and in one of the two animals at the 48 hours. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. One female was devoid of any local signs at any observation time. (see attached table 1)
Interpretation of results:
not 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), TRIQUAT Monomer is considered to be “not irritating” to the rabbit eye.
Executive summary:

The primary eye irritation potential of TRIQUAT Monomer was investigated according to OECD test guideline no. 405. The test item was applied by instillation of 0.1 mL into the left eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours after test item instillation.

The instillation of TRIQUAT Monomer into the eye resulted in mild, early-onset and transient ocular changes, such as conjunctival and scleral reddening as well as conjunctival chemosis in the male and one female.The conjunctival effects were no longer evident from 24 hours after treatment. The scleral reddening persisted in both animals at the 24 hours and in one of the two animals at the 48 hours. No abnormal findings were observed in the cornea or iris of any animal at any of the examinations. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed and no clinical signs were observed. One female was devoid of any local signs at any observation time.

Thus, the test item did not induce significant or irreversible damage to the rabbit eye.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after instillation) for each animal for corneal opacity, iris, redness and chemosis of the conjunctivae, separately. The individual mean scores for corneal opacity and iris were 0.00 for all three animals. The individual mean scores for the conjunctival reddening and chemosis were 0.00 for each of the

three animals.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The in vivo studies conducted according to current standards showed no signs of irritation on contact with skin or eyes.


Justification for selection of skin irritation / corrosion endpoint:
In vivo study in compliance with current EC method/OECD guidelines, and GLP standards.

Justification for selection of eye irritation endpoint:
In vivo study in compliance with current EC method /OECD guidelines, and GLP standards.

Justification for classification or non-classification

All the available experimental studies showed no signs of irritation to the skin and eyes. The substance is not classified according to EU criteria for classification (CLP Regulation 1272/2008 and EU Directive 67/548/EEC).