Registration Dossier

Administrative data

Description of key information

Guideline, GLP skin and eye irritation studies are available for cloquintocet-mexyl technical (purity 91.6%). There was evidence of mild skin irritation which had fully reversed after 48 hours. There was some evidence of eye irritation which had fully reversed after 72 hours.  The irritation seen was not of sufficient severity to warrant classification as a skin or eye irritant.
There is no data on respiratory irritation.

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:
27 January 1987 to 30 January 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2190 to 2320 g
- Housing: not specified
- Diet (e.g. ad libitum): not specified
- Water (e.g. ad libitum): not specified
- Acclimation period: not specified

IN-LIFE DATES: From: 27.01.1987 To: 30.01.1987
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: site moistened with distilled water containing 0.5% CMC and 0.1% polysorbate 80
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 g
- Concentration (if solution): not applicable

Duration of treatment / exposure:
4 hours
Observation period:
72 hours after removal of the treatment
Number of animals:
Three male rabbits
Details on study design:
TEST SITE
- Area of exposure: 36 cm2 of flank exposed, 0.5 g of test powder applied under small gauze
- Type of wrap if used: gauze patch covered by aluminium foil, secured around trunk by adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): not specified
- Time after start of exposure: not specified

SCORING SYSTEM: OECD Draize assessment method
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
>= 0.22
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Remarks on result:
other: Two rabbits had scores of 1 for erythema after 24 hours.
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24, 48 and 72 hours
Score:
0
Max. score:
4
Reversibility:
other: not applicable
Irritant / corrosive response data:
Very slight erythema was evident for two rabbits at one and 24 hours. No other reactions were noted.
Other effects:
None

Table 1: Summary of results

Erythema and Eschar

Animal no.

1 M

2 M

3 M

after 1 hour

1

1

1

after 24 hours

1

0

1

after 48 hours

0

0

0

after 72 hours

0

0

0

mean score 24 to 72 h

0.22

Oedema

after 1 hour

0

0

0

after 24 hours

0

0

0

after 48 hours

0

0

0

after 72 hours

0

0

0

mean score 24 to 72 h

0

M: Male

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Very slight erythema was reported at the one and 24 hour observation times. No reactions were recorded at 48, and 72 hours. According to the Commission Directive 2001/59/EC the mean values of the scores between 24 to 72 hours after application were below the threshold for classification as an Irritant.
Executive summary:

Cloquintocet-mexyl technical, purity 91.6%, batch P. 607001/002. The solid test material was applied to a gauze patch moisturized with distilled water containing 0.5% CMC and 0.1% polysorbate 80 which was placed on the shaved flank of three male albino NZW rabbits. Flanks were shaved 24 hours before dosing. 0.5 g of cloquintocet-mexyl applied to the skin on a gauze patch, was covered with aluminium foil and fastened around the trunk by an adhesive tape to form an occlusive dressing. The patch was held in place for 4 hours. Skin reactions were evaluated according to the OECD scoring system after 1, 24, 48 and 72 hours. Very slight erythema was reported at the one hour observation time in all three rabbits and at 24 hours in two rabbits. The erythema had fully reversed at 48 hours. Cloquintocet-mexyl is non-irritating to the 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:
24 December 1987 to 03 March 1987
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Principles of method if other than guideline:
Not applicable
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: not specified
- Age at study initiation: 12-14 weeks
- Weight at study initiation: 2180 to 2550 g
- Housing: conventional laboratory housing units not otherwise specified
- Diet (e.g. ad libitum): not specified
- Water (e.g. ad libitum): not specified
- Acclimation period: not specified

IN-LIFE DATES: From: 24.02.1987 To: 03.03.1987
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
The report indicates 0.1 mL (a weight of 48 mg) was instilled into each treated eye
Duration of treatment / exposure:
The eyes were examined over a period of 7 days. No rinse out procedures were included to flush the test material away at any point
Observation period (in vivo):
Observation and assessment of ocular damage completed at 1, 24, 48 and 72 hours post-instillation and again after 7 days
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Standard Draize method

TOOL USED TO ASSESS SCORE: None specified - simple visual checks only
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight reactions observed in all three rabbits at 1, 24 and 48 hour assessments
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0
Max. score:
2
Reversibility:
other: Not applicable.
Remarks on result:
other: No iridial changes were apparent
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
1.2
Max. score:
3
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Slight to well defined erythema evident for all three treated eyes at assessments in first 48 hours after instillation. All reactions had resolved within 72 hours
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24, 48, 72 hours
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Remarks on result:
other: Very slight to slight chemosis evident for all three treated eyes in the first 48 hours after dosing. Fully recovered by the 72 hour assessment
Irritant / corrosive response data:
Signs of irritation were evident 1, 24 and 48 hours following instillation affecting the conjunctivae and cornea. No adverse effects noted for the iris.
All signs of irritation had resolved within 72 hours

Table 1: Summary of results

Cornea

Iris

Animal no.

 1 M

2 M

 3 M

1 M

2 M

3 M

after 1 hour

1

0

0

0

0

0

after 24 hours

1

1

1

0

0

0

after 48 hours

1

1

1

0

0

0

after 72 hours

after 7 days

0

0

0

0

0

0

0

0

0

0

0

0

mean score 24, 48, 72 h

0.67

0

Conjunctival redness

Conjunctival chemosis

after 1 hour

1

1

1

2

1

2

after 24 hours

2

2

2

1

1

1

after 48 hours

2

1

2

1

1

1

after 72 hours

after 7 days

0

0

0

0

0

0

0

0

0

0

0

0

mean score 24, 48, 72 h

1.2

0.67

M: Male 

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Cloquintocet-mexyl does not trigger classification for eye irritation.
Executive summary:

To evaluate eye irritation potential, 0.1 mL (48 mg) of cloquintocet-mexyl technical, purity 91.6%, batch P. 607001/002 was placed into the conjunctival sac of one eye of three male New Zealand White Rabbits. Ocular reactions were evaluated at 1, 24, 48, and 72 hours and 7 days following treatment. The results showed transient slight irritating effects in the cornea and conjunctivae that had fully resolved within 72 hours. Cloquintocet-mexyl does not trigger classification for eye irritation.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

Cloquintocet-mexyl has been tested in rabbits (Schoch M, 1987). There was evidence of slight erythema after 1 and 24 hours which had fully reversed after 48 hours. There was no evidence of corrosion. 

Eye irritation

Data on cloquintocet-mexyl indicate that instillation of liquid test substance into the conjunctival sac of the rabbit eye induced some irritation at 24 and 48 hours which had fully reversed after 72 hours. None of the eye findings were of a severity that warrants classification (Schoch M, 1987).

Respiratory irritation

There are no data.

Human information

There is no human information concerning skin or eye irritation.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available

Justification for selection of eye irritation endpoint:
Only one study available

Justification for classification or non-classification

Although there is some evidence of skin and eye irritation in response to administration of cloquintocet-mexyl, this is fully reversible and is not of sufficient severity to warrant classification:

- under Directive 67/548/EEC, as amended for the 28th time in Directive 2001/59/EC, Annex VI, 3.2.5 and 3.2.6.

- under Regulation (EC) 1272/2008, Annex I, Part 3, 3.2.

- under Regulation (EC) 1272/2008, Annex I, Part 3, 3.3.