Desmedipham

Endpoint summary

Description of key information

In vitro testing for skin corrosion and skin irritation is not required, based on the availability of older in vivo studies performed prior to the validation and adoption of the in vitro methods.  The key (K1) study of skin irritation in the rabbit performed to GLP and OECD 404 does not report any skin irritation.  The supporting (K1) study of skin irritation in the rabbit performed to GLP and OECD 404 does not report any skin irritation.

In vitro testing for eye irritation is not required, based on the availability of older in vivo studies performed prior to the validation and adoption of the in vitro methods.  The key (K1) study of eye irritation in the rabbit performed to GLP and OECD 405 reports mild and transient eye irritation.  The supporting (K1) study of eye irritation in the rabbit performed to GLP and OECD 405 reports mild and transient eye irritation. 

There are no specific studies of respiratory irritation; however, there is no evidence of respiratory irritation from the acute inhalation toxicity study.

Test method/  species	Result	Assessment	Reference
OECD 404 - Rabbit study	Desmedipham was not found to be a skin corrosive or skin irritant.	Key study	Cuthbert and Jackson (1991)
OECD 404 - Rabbit study	Desmedipham was not found to be a skin corrosive or skin irritant.	Supporting study	Ullmann and Suter (1984)
OECD 405 - Rabbit study	Desmedipham was not found to be an eye irritant.	Supporting study	Ullmann and Suter (1984)
OECD 405 - Rabbit study	Desmedipham was not found to be an eye irritant.	Key study	Cuthbert and Jackson (1991)

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:

1990-10-28 to 1991-03-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

The test material, a white powder, was stored in the dark under ambient conditions.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: adults.
- Weight at study initiation: Not provided.
- Housing: individually in aluminium cages with grid floors beneath which were peat moss filled trays.
- Diet: Standard Rabbit Diet, ad libitum.
- Water: ad libitum.
- Acclimation period: 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 18
- Mean Relative Humidity (%): 67
- Air changes (per hr): Not provided.
- Photoperiod: 12 h light/dark cycle (light hours 0700-1900 h).

The rabbits were uniquely identified within the study by means of an indelible number on the inner surface of the ear.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Remarks:

Approximately 24 h before treatment. Care was taken to avoid abrading the skin.

Vehicle:

water

Controls:

not required

Amount / concentration applied:

0.5 g, moistened with water

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48 and 72 h after patch removal

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: Dorsal area of the trunk of each rabbit.
- % coverage: Not provided.
- Type of wrap if used: The patch was then covered with Micropore tape and the trunk was loosely bound with Elastoplast Elastic Bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the patches were removed and the skin wiped with water dampened tissues to remove surplus test material without altering the existing response or the integrity of the epidermis.
- Time after start of exposure: 4 hours

OBSERVATION TIME POINTS
1, 24, 48 and 72 h after patch removal

SCORING SYSTEM:
- Method of calculation: OECD Recommended Scoring System:

1- Erythema and Eschar Formation:
No erythema: 0
Very slight erythema (barely perceptible): 1
Well defined erythema: 2
Moderate to severe erythema: 3
Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4

2- Oedema Formation:
No oedema: 0
Very siight oedema (barely perceptible): 1
Slight oedema (edges of area well defined by definite raising): 2
Moderate oedema (area raised approximately 1 mm): 3
Severe oedema (raised by more than 1 mm and extending beyond area of exposure): 4

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Table 1:
Desmedipham: Acute Dermal Irritation Test in Rabbits Reaction Scores

Animal/sex	Erythema				Oedema
	1 h	12 h	24 h	72 h	1 h	12 h	24 h	72 h
1/male	0	0	0	0	0	0	0	0
2/male	0	0	0	0	0	0	0	0
3/male	0	0	0	0	0	0	0	0

h = Hours after patch removal

Interpretation of results:

GHS criteria not met

Conclusions:

Desmedipham is non-irritant to rabbit skin and does not require classification for skin irritation in any category according to the CLP criteria.

Executive summary:

The acute dermal irritation potential of Desmedipham, was investigated in 3 New Zealand White rabbits. No skin reactions were noted following a 4 hour semi-occlusive application of Desmedipham to rabbit skin. Desmedipham is non-irritant to rabbit skin and does not require classification for skin irritation in any category according to the CLP criteria.

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:

1990-11-24 to 1991-03-18

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

The test material is in a white powder form.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: Young adults.
- Weight at study initiation: Not provided.
- Housing: Individually in aluminium cages with grid floors beneath which were peat moss filled trays.
- Diet: Standard Rabbit Diet, ad libitum.
- Water: ad libitum
- Acclimation period: 12 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-19
- Mean Relative Humidity (%): 57
- Air changes (per hr): Not provided.
- Photoperiod: 12 h light/dark cycle (light hours 0700-1900 h).

The rabbits were uniquely identified within the study by an indelible number on the inner surface of the ear.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 100 mg

Instillation of the test material was by the following technique:
The rabbit was held firmly but gently and the test material placed into the right eye by gently pulling the lower eyelid away from the eyeball to form a sac into which the test material was dropped. The lids were then gently held together for 1-2 seconds.

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

One rabbit was treated first and observed up to 24 h after instillation for signs of severe irritation. As none were noted, the remaining 2 rabbits were then treated. The eyes were examined for irritation and ocular reactions were recorded 1, 24, 48 and 72 h after instillation.

Number of animals or in vitro replicates:

3 animals

Details on study design:

Approximately 24 h before test commencement, both eyes of the rabbits were examined and only animals with no ocular defects were used in the test.

SCORING SYSTEM:

TOOL USED TO ASSESS SCORE: The eyes were examined for irritation, using a hand held magnifier and pen torch.

OECD Recommended Scoring System:

CORNEA:
1- 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 area, no details of iris visible, size of pupil barely discernible - 3
Opaque cornea, iris not discernible through the opacity - 4

2- Area of Opacity
A quarter (or less) but not more - 1
Between a quarter and a half - 2
Between half and three quarters - 3
Between three quarters and the whole surface - 4

IRIS:
Normal - 0
Markedly deepened folds, congestion, swelling, moderate circumcorneal hyperaemia or injection (any of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive) - 1
No reaction to light, haemorrhage, gross destruction (any or al 1 of these) - 2

CONJUNCTIVAE:
1- Redness (refers to palpebral and bulbar conjunctivae):
Blood vessels normal - 0
Some blood vessels definitely hyperaemic (injected) - 1
Diffuse, crimson colour, individual vessels not easily discernible - 2
Diffuse beefy red - 3

2- Chemosis (lids and/or nictitating membranes):
No swelling - 0
Any swelling above normal (including nictitating membranes) - 1
Obvious swelling with partial eversion of lids - 2
Swelling with lids about half closed - 3
Swelling with lids more than half closed - 4

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.22

Max. score:

3

Reversibility:

fully reversible within: persisting until 48 h in one treated eye. All treated eyes were normal by 72 h post instillation.

Remarks on result:

probability of weak irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: Not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Details of reaction scores are given in the table below.

No corneal or iridial responses were noted.

Slight conjunctival redness and a slight discharge were noted 1 h post instillation with slight redness persisting until 48 h in one treated eye. All treated eyes were normal by 72 h post instillation.

Table 1: Desmedipham: Acute Eye Irritation Test in Rabbits Reaction Scores

Area of Eye

Observation Time/ Animal /Sex/Score

1 h

24 h

48 h

72 h

4/male

5/male

6/male

4/male

5/male

6/male

4/male

5/male

6/male

4/male

5/male

6/male

Cornea: degree/opacity area/opacity   Iris   Conjunctivae: redness chemosis   Discharge

0 0   0     1 0   -

0 0   0     1 0   SL

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     1 0   -

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     1 0   -

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     0 0   -

0 0   0     0 0   -

Interpretation of results:

GHS criteria not met

Conclusions:

Desmedipham is practically non-irritant to rabbit eyes and does not require classification for eye irritation in any category according to the CLP criteria.

Executive summary:

The eye irritation potential of Desmedipham, was investigated in 3 New Zealand White rabbits. Slight conjunctival redness and a slight discharge were noted at 1 h post instillation with slight redness persisting until 48 h post instillation in one treated eye. Desmedipham is practically non-irritant to rabbit eyes and does not require classification for eye irritation in any category according to the CLP criteria.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available