Alkyl phosphites

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Testing was carried out to GLP standards in accordance with OECD guideline 404. Some details on test material are missing.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

and EU Method B4 (Acute Dermal Irritation/Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: HRP Inc, Denver, PA
- Age at study initiation: 14 weeks
- Weight at study initiation: 2.39 kg
- Housing: Singles housed in suspended stainless steel wire mesh.
- Diet: Agway Certified Diet R.C.A Rabbit (Agway Inc, Waverly, NY) Ad libitum
- Water: Ad libitum
- Acclimation period: 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21 °C
- Humidity (%): 40 to 60%
- Air changes (per hr): Not stated.
- Photoperiod (hrs dark / hrs light): 12 hours light (07:00 to 19:00) 12 hours dark (19:00 to 07:00).

IN-LIFE DATES: From: To: 1996-05-06 to 1996-05-20

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL (undiluted test material was adminstered neat)

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours.

Observation period:

14 days.

The animal was examined for viability twice daily Monday to Friday, and once daily on weekends. Body weights were recorded on the day of dosing (Day 0) and at terminal sacrifice (Day 14).

Dermal responses were evaluated at 60 minutes, 24 hours, 48 hours and 72 hours following patch removal, and on Days 7, 10 and 14.

Number of animals:

1 Male

Details on study design:

TEST SITE
- Area of exposure: 1 inch x 1 inch
- Test Site Preperation: Approximately 24 hours prior to topical adminstration of the test materia, the hair of the rabbit in the area of the dorsal surface from the shoulder region to the lumbar region was closely clipped with an electric clipper. The skin was left intact. An elizabethan-type collar was placed around the neck of the rabbit at this time to acclimiate him to wearing a collar. The animal was reclipped as necessary. The collar remained on the animal for approximately 29.5 hours.
- Adminstration of Test Material: The test material was administered as three 0.5 mL doses, each introduced under a 1 inch x 1 inch gauze patch, then secured with non irritating tape. Each patch was loosely held in contact with the skin by means of a semi-occlusive dressing for the duration of the exposure period. After at least 3 minutes of exposure, the dressing and gauze patch were removed from the first site. After at least 1 hour, the dressing and gauze patch were removed from the second site. After at least 4 hours, the dressing and gauze patch were removed from the third test site.
- Type of wrap if used: Gauze patch secured by non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Removal of residual test material using peanut oil and a paper towel.
- Time after start of exposure: 3 minutes, 1 hour and 4 hours.
- The collar was removed after the 4 hour exposure.

SCORING SYSTEM: Draize 1959.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

3 min exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14

Results 2

Irritation parameter:

erythema score

Remarks:

1 hour exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 3

Irritation parameter:

erythema score

Remarks:

4 hours exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 4

Irritation parameter:

edema score

Remarks:

3 min exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 14 days

Results 5

Irritation parameter:

edema score

Remarks:

1 hour exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.33

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 6

Irritation parameter:

edema score

Remarks:

4 hour exposure

Basis:

animal #1

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not fully reversible within: 14 days

Results 7

Irritation parameter:

other: 3 min exposure

Basis:

animal #1

Remarks on result:

other: atonia, lethary skin, exfoliation and desquamation observed

Results 8

Irritation parameter:

other:

Remarks:

1 hour exposure

Basis:

animal #1

Remarks on result:

other: blanching, necrosis, eschar, lethary skin, exfoliation and desquamation observed

Results 9

Irritation parameter:

other:

Remarks:

4 hour exposure

Basis:

animal #1

Remarks on result:

other: blanching, necrosis, eschar, lethary skin, exfoliation and desquamation observed

Irritant / corrosive response data:

This study was conducted to evaluate the dermal irritation and potential corrosivity of three 0.5 ml doses of the test material in the rabbit following 3 minutes, 1 hour, and 4 hours of exposure. Full table of results can be found in attachment 1.
 
Skin Responses - 3 Minute Exposure
 
Topical application of the test material elicited very slight erythema at 60 minutes following exposure. Moderate/severe erythema and moderate edema were noted at 24 Hours. At 48 and 72 Hours, well-defined erythema and slight edema were observed. Atonia was also noted at 72 Hours. Irritation decreased asthe study progressed with only very slight erythema being noted on Days 7 and 10.Very slight edema, as well as leathery skin and exfoliation, were noted on Day 7.Desquamation was noted on Days 10 and 14. There was no evidence of erythema
or edema on Day 14.
 
Skin Responses - 1 Hour Exposure
 
Severe erythema and edema (ranging from very slight to severe) were noted at every scoring interval. Necrosis was noted at 60 minutes and at 24, 48, and 72 Hours. Blanching was noted at 60 minutes and 24 Hours. Leathery skin was noted at 48 and 72 Hours and on Day 14. Eschar was noted on Days 7, 10, and 14. Desquamation was noted on Days 10 and 14, and exfoliation was noted on Day 7.
 
Skin Responses - 4 Hour Exposure
 
Severe erythema and edema (ranging from very slight to severe) were observed from the 60 minute interval to Day 7. Severe erythema persisted on Day 10, but no edema was noted. Irritation decreased by Day 14 when only very slight erythema and edema were noted. Necrosis was noted at 60 minutes and at 24, 48, and 72 Hours. Blanching was noted at 60 minutes and 24 Hours. Leathery skin was noted at 48 and 72 Hours, and on Day 10. Eschar was noted on Days 7 and 10. Exfoliation was noted on Day 7 and desquamation was noted on Days 10 and 14.

Other effects:

Overt signs of corrosivity (blanching and/or necrosis) were observed in this animal at the 1 hour and 4 hour exposure sites at 60 minute, 24, 48 and 72 hour dermal evaluations. There was no sign of corrosivity at the three minutes exposure site during the test period.

Applicant's summary and conclusion

Interpretation of results:

Category 1B (corrosive)

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In conclusion the test material was corrosive under the conditions of this study.

Executive summary:

This study was conducted in order to evaluate the dermal irritation and potential corrosivity of the test material in the rabbit.

 

The test material was administered as three 0.5 ml doses introduced under separate gauze patches to one animal. The patches were secured with non-irritating tape and were loosely held in contact with the skin by means of a semi-occlusive dressing. Exposure duration of each dose site varied, with one of the three dressings remaining in place for either three minutes, one hour, or four hours. After the appropriate exposure was completed, the dressing and gauze were removed. Residual test material was removed using peanut oil and paper towels. Each test site was graded for erythema, edema and other signs of dermal irritation at 60 minutes, 24, 48, and 72 Hours after patch removal, and on Days 7, 10 and 14. All dermal scoring was made according to the Draize method (Draize, 1959).

 

In an attempt to minimize animal pain and distress, only one animal was initially dosed at all three exposures sites. Since this animal showed signs of corrosivity (blanching/necrosis) no other animals were dosed as per the OECD guideline 404. The one dosed animal was observed for 14 days to evaluate fully the reversibility or irreversibility of the effects observed.

 

The animal survived to study termination on Day 14, displayed an increase in body weight, and was not observed with any unusual clinical signs.

 

Overt signs of corrosivity (blanching and/or necrosis) were observed in this animal at the 1 Hour and 4 Hour exposure sites at the 60 minute, 24, 48, and 72 Hour dermal evaluations. There was no sign of corrosivity at the three minutes exposure

site during the test period.

 

At the four hour exposure site, severe erythema and edema (ranging from very slight to severe) were observed from the 60 minute to Day 7 observation intervals. Severe erythema persisted, but no edema was noted on Day 10. Irritation decreased by the Day 14 observation when only slight erythema and edema were noted. In addition to blanching and necrosis, other supplemental dermal observations at the 4 hour site included desquamation, exfoliation, leathery skin and eschar. The irritation observed at the 1 Hour exposure was essentially equivalent to the irritation seen at the 4 Hour exposure. Irritation observed at the 3 minute exposure was slightly reduced and there were no apparent signs of corrosivity.

 

In conclusion, the test material was corrosive under the conditions of this study.