cis-4-[3-(p-tert-butylphenyl)-2-methylpropyl]-2,6-dimethylmorpholine

Endpoint summary

Description of key information

Fenpropimorph has shown skin irritating properties in a GLP guideline study according to OECD guideline 404. However, no corrosive properties have been observed; neither in this study nor in an in vitro EpiDerm test. There are some older studies available, which have not been included in this dossier, because they all have been performed under occlusive conditions.

Fenpropimorph is not irritating to the eye according to an OECD 405 GLP guideline study.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion, other

Remarks:

Acute dermal irritation / corrosion in rabbits

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10.2010 - 12.2010

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:

April 24, 2002

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

certified by Umweltministerium Baden-Württemberg

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl:KBL(NZW)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Ca. 5 months
- Weight at study initiation: 3.93 - 4.23 kg
- Housing: single housing
- Diet: STANRAB (P) SQC, not specified if ad libitum or not
- Water: Tap water, ad libitum
- Acclimation period: At least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature: 20 ± 3°C
- Humidity: 30 - 70 %
- Air changes: not specified
- Photoperiod: 12 h / 12 h (6.00 a.m. - 6.00 p.m. / 6.00 p.m. - 6.00 a.m.)

IN-LIFE DATES:
- From: 2010-10-26
- To: 2010-11-30

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 mL of the undiluted liquid test item

NEGATIVE CONTROL : untreated skin sites of the same animal
- Amount(s) applied (volume or weight): not applicable
- Concentration (if solution): not applicable

POSITIVE CONTROL : not applicable

Duration of treatment / exposure:

4 hours

Observation period:

14 days

Number of animals:

3 males

Details on study design:

TEST SITE
- Area of exposure: Flank
- % coverage: 2.5 cm x 2.5 cm
- Type of wrap if used: semi occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Washing: The test item was removed with Lutrol E 400 and Lutrol / water (1:1)
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
Immediately after removal of the patch, approx. 1, 24, 48 and 72 hours after removal and then in weekly intervals up to day 14.

SCORING SYSTEM:
- Method of calculation: For evaluation the mean values of erythema and edema for readings at 24, 48 and 72 hours were calculated. Additionally, reversibility of the observed findings was evaluated.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

fully reversible within: within 14 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.7

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritant / corrosive response data:

- Erythema beyond the application area was observed in all animals during the course of the study
- Edema beyond the application area was noted in one animal immediatly after removal of the patch and at the 1 hour reading
- Scaling occured in all animals from day 7 to the study termination
- The test item shows a skin irritating potential under the test conditions chosen

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

Dec 2010 - Mar 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

April 24, 2002

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: Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: Ca. 3 months
- Weight at study initiation: 2.24 - 2.65 kg
- Housing: single
- Diet: STANRAB (P) SQC (not specified if ad libitum or not)
- Water: Tap water, ad libitum
- Acclimation period: at least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30 - 70%
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. - 6.00 p.m. / 6.00 p.m. - 6.00 a.m.)

IN-LIFE DATES:
- From: 2011-01-10
- To: 2011-02-22

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent negative control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL

Duration of treatment / exposure:

24 hours

Observation period (in vivo):

1, 24, 48 and 72 hours after application and in weekly intervals until study day 21

Number of animals or in vitro replicates:

3 animals

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The treated eye of the animal(s) was rinsed with 3 to 6 ml of hand warm tap water for 1 to 2 minutes using a syringe with a blunt probe
- Time after start of exposure: 24 hours after application

SCORING SYSTEM: For evaluation mean values of corneal opacity, iris, conjunctival redness and chemosis for readings 24, 48 and 72 hours were calculated. Additionally, the reversibility of the observed findings was evaluated . (For more details: see section "Any other information on materials and methods incl. tables")

TOOL USED TO ASSESS SCORE: slit and otoscope lamp, additionally fluorescein (24 h after application)

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 21 days

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within: 14 days

Irritation parameter:

iris score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

- Lesions and clinical observations: No corneal and iris lesions were noted in any animal at any examination timepoint. Slight conjunctival redness, slight or moderate conjunctival chemosis (grade 1 or 2) and initially (at the one hour reading) obvious or severe discharge were observed in the animals during the course of the study. Additional findings like incrustations (circular, upper or lower lid, marginal or severe degree), scaling (lower lid), small retraction in the eyelid, loss of hair (circular, upper or lower lid) and injected scleral vessels in a circumscribed or circular area were noted in the animals during the observation period.
The ocular reactions were reversible in all animals within 21 days after application.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Justification for classification or non-classification

Fenpropimorph is classified for skin irritation (Cat.2, H315) according to EC/1272/2008 Annex VI. It does not need to be classified for eye irritation according to CLP criteria.