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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From Dec.10, 2009 to Jan.15, 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study was conducted according to OECD Test Guideline 404, in compliance with GLP. The test substance characterization, provided by the sponsor, was not conducted according to the Good Laboratory Practices. However, it was approved under ISO 9001:2008 .

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Remarks:
The test substance characterization, provided by the sponsor, was not conducted according to the Good Laboratory Practices. However, it was approved under ISO 9001:2008 .

Test material

Constituent 1
Reference substance name:
Trioctylphosphine oxide (TOPO)
IUPAC Name:
Trioctylphosphine oxide (TOPO)
Constituent 2
Chemical structure
Reference substance name:
Trioctylphosphine oxide
EC Number:
201-121-3
EC Name:
Trioctylphosphine oxide
Cas Number:
78-50-2
Molecular formula:
C24H51OP
IUPAC Name:
trioctylphosphine oxide
Test material form:
other: Solid
Details on test material:
- Name of test material (as cited in study report): CYANEX® 921 Extractant
- Physical state: white solid
- Analytical purity: 90%
- Lot/batch No.: WE7060753
- Expiration date of the lot/batch: 6 months from date of receipt
- Certificate of analysis: CVANEX921 dated 01-Dec-2009
- Storage condition of test substance: at room temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
- Source: Covance Research Products Inc., Denver. PA
- Housing: animals were individually housed in suspended cages
- Identification: the animals were identified by cage notation and a uniquely numbered metal ear tag
- Body weight range before the test: 2.8-3.0 kg
- Diet: fresh PMI Rabbit Chow (Diet #5321
- Water: ad libitum
- Photoperiod: 12 h light/dark cycle

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: Distilled water
Amount / concentration applied:
500 mg/patch
Duration of treatment / exposure:
Rabbit 1: Site #1 exposure: 3 minutes postdose, site #2: 1 h postdose and site #3: 4 h postdose
Rabbit 2 and 3: 4 h postdose
Observation period:
The test sites of all animals were scored for dermal irritation at 60 min after removal of wrappings. Site #3 was scored at 24, 48 and 72 h and on Day 7 and 14 following patch removal for animals #H2936/F and H3001/F. Animal #H3002/F was scored at 24, 48 and 72 h and again on Day 7, 14, 15, 16 and 17.
Number of animals:
3
Details on study design:
Frequency of administrations: single dose
Preparation of the test substance: each animal was treated with 500 mg of test substance formed into a paste with 0.5 mL distilled water.
Test procedure:
Each dose site was approximately 9 cm2. Initially, one rabbit was dosed sequentially on sites #1, 2, and 3. The test substance was applied under a 2.5 x 2.5 cm gauze patch. Gentle pressure was applied to aid the distribution of the test substance over the prepared site. The rabbit was gently held in place and a piece of porous dressing was secured with non-irritating tape over dose site #1 (semi-occlusive) for the 3 min exposure period. The torso was covered with a piece of porous dressing large enough to cover dose sites #2 and 3 with at least 5 cm2 to spare on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal. The dressing and test substance patch covering site #1 were removed at 3 min after dosing, over site #2 at 1 h after dosing and the torso wrappings and patch covering site #3 at 4 h after dosing. All sites were gently washed with distilled water to remove residual test substance.
Two additional animals were added to the study. The animals were dosed at site #3 with 0.5 g of the test substance.
After an exposure period of 4 h, the wrappings and patches were removed and the sites were gently washed with distilled water.

Type of Observations: erythema, eschar formation and edema were evaluated numerically according to the score of Draize. All other changes of the skin were recorded.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
3.33
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #1
Time point:
other: 24, 48 and 72 h
Score:
2.67
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #2
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal #3
Time point:
other: 24, 48 and 72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 14 d
Irritant / corrosive response data:
Initial animal: No erythema and no edema was observed at 60 minutes after patch removal following the 3 minute exposure. Well defined erythema and no edema was observed at 60 minutes after patch removal following the 1 h exposure and well defined erythema and very slight edema was observed at 60 minutes after patch removal following the 4 h exposure. Erythema was moderate at 24 and 48 h and severe at 72 h following the 4 h exposure. Dark areas and cracking skin were observed at 48 h. By Day 7, erythema was well defined with eschar and flaking skin and absent on Day 14. Slight edema was observed at 24 h and moderate edema was observed at 48 and 72 h following the 4 h exposure. By Day 7 slight edema was observed and no edema was observed on Day 14.

Additional animals: Erythema was well defined 60 minutes after patch removal and very slight to well defined at 24 and 48 h. Very slight edema was observed at 72 h following the 4 h exposure. Flaking skin was observed at 24 h and cracking skin at 48 and 72 h. On Day 7, very slight erythema with flaking skin was observed. On Day 14, erythema was well defined for one animal (#H3002) with a shiny area, while the other animal had no erythema with some flaking skin. Animal# H3002 continued to be observed until no erythema was noted. Erythema was well defined on Day 15, very slight on Day 16 and absent on Day 17. Edema was very slight to slight 60 minutes after patch removal and very slight at 24, 48 and 72 h following the 4 h exposure. Edema was absent on Day 7, 14, 15, 16 and 17.
Other effects:
Systemic Observations- There were no abnormal physical signs noted during the observation period.
Body Weights- Body weight changes were normal.

Any other information on results incl. tables

Modified Primary Irritation Index (PDII) was calculated by adding mean erythema/eschar and edema values on the 4 h exposure, of all animals at 24 and 72 h (a total of 4 values) and dividing the sum by 2.

Table: Calculation of Modified Primary Irritation Index (PDII):

Mean erythema scores

Mean edema scores

24 h

72 h

24 h

72 h

2.00

2.00

1.33

1.67

Sum of Mean Scores =7.00

Modified Primary Irritation Index (PDII) = Sum of Mean Scores/2 = 3.50

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The test substance was found to be irritating to skin (DiDonato LJ, 2010).
Executive summary:

A study was conducted to evaluate the skin irritation potential of the test substance in rabbits according to OECD Guideline 404, in compliance with GLP. 0.5 g of test substance was moistened with 0.5 mL of distilled water to form a pasty consistency and applied at each test site under a 2.5 x 2.5 cm gauze patch, using semi-occlusive conditions. After an exposure period of 4 h, the wrappings and patches were removed and the sites gently washed with distilled water. The test sites were scored for signs of dermal irritation at 1, 24, 48 and 72 h as well as on Day 7, 14 and 17 after removal of the patches. Erythema and edema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional clinical signs were noted. Under the study conditions, the test substance was found to be irritating to skin (DiDonato LJ, 2010).