Registration Dossier

Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1998-08-11 to 1998-08-25
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented guideline study in compliance with GLP (conducted with a read-across substance)

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Department of Health of the Government of the United Kingdom

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: viscous liquid
Details on test material:
- Molecular formula (if other than submission substance): C28H62NO4P (for a representative structure: Phosphoric acid, di(C8)ester, compds with C12 amine)
- Molecular weight (if other than submission substance): 507.76
- Smiles notation (if other than submission substance): CCCCCCCCCCCCN.O=P(O)(OCCCCCCCC)OCCCCCCCC
- InChl (if other than submission substance): InChI=1/C12H27N/c1-2-3-4-5-6-7-8-9-10-11-12-13/h2-13H2,1H3
- Physical state: extremely pale straw coloured viscous liquid
- Storage condition of test material: room temperature in the dark
- Other: Data relating to the identity, purity and stability of the test material are the responsibility of the Sponsor.

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: twelve to sixteen weeks
- Weight at study initiation: 2.75 to 2.90 kg
- Housing: individually housed in suspended metal cages
- Diet/Water (e.g. ad libitum): free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK)
- Acclimation period: five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 25
- Humidity (%): 65 to 74
- Air changes (per hr): approximately fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light and twelve hours darkness

Test system

Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
2 males / 1 female
Details on study design:
TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: strip of surgical adhesive tape (BLENDERM: approximate size 2.5 cm x 4.0 cm); wrapped in an elasticated corset (TUBIGRIP)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Corset and patches were removed from each animal and any residual test material removed by gentle swabbing with cotton
wool soaked in distilled water.

SCORING SYSTEM:
-Method by Draize

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal: 1
Time point:
other: 24 h, 48 h, 72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal: 2
Time point:
other: 24 h, 48 h, 72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
erythema score
Basis:
animal: 3
Time point:
other: 24 h, 48 h, 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal: 1
Time point:
other: 24 h, 48 h, 72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal: 2
Time point:
other: 24 h, 48 h, 72 h
Score:
1.7
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritation parameter:
edema score
Basis:
animal: 3
Time point:
other: 24 h, 48 h, 72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 d
Irritant / corrosive response data:
- Well-defined erythema (24 and 48-hour observations);
- Well-defined erythema to very slight erythema (72-hour observation);
- Moderate oedema, slight oedema (1-hour observation);
- Slight oedema (24 and 48-hour observations);
- Slight oedema, very slight oedema (72-hour observation).
Other effects:
Loss of skin elasticity (48 and 72-hour observation), crust formation (7 days after treatment): fully reversible within 14 days.

Any other information on results incl. tables

Well defined erythema was noted at all treated skin sites one hour after patch removal and at the 24 and 48-hour observations. Well-defined erythema was noted at one treated skin site with very slight erythema at two treated skin sites at the 72-hour observation.

Moderate oedema was noted at one treated skin site with slight oedema at two treated skin sites one hour after patch removal. Slight oedema was noted at all treated skin sites at the 24 and 48-hour observations. Slight oedema persisted at one treated skin site with very slight oedema at two treated skin sites at the 72-hour observation.

Loss of skin elasticity was noted at one treated skin site at the 48-hour observation and at all treated skin sites at the 72-hour observation. Crust formation was noted at one treated skin site with slight desquamation at two treated skin sites at the 7-day observation. Treated skin sites appeared normal at the 14-day observation.

Table 1. Individual Skin Reactions

Skin Reaction Observation Time Individual Scores - Rabbit Number and Sex (Bodyweight kg) Total
10 Male (2.75) 36 Male (2.90) 78 Male (2.88)
Erythema/Eschar Formation 1 Hour 2 2 2 ( 6 )
24 Hours 2 2 2 6
48 Hours 2 2 2 Le (6)
72 Hours 1 Le 1 Le 2 Le 4
7 Days 0 D 0 D 0 Cf (0)
14 Days 0 0 0 (0)
Oedema Formation 1 Hour 2 3 2 ( 7 )
24 Hours 2 2 2 6
48 Hours 2 2 2 (6 )
72 Hours 1 1 2 4
7 Days 0 0 0 (0 )
14 Days 0 0 0 (0)
Sum of 24 and 72-hour Readings (S)   20      
Primary Irritation Index (S/6)   20/6 = 3.3      
Classification  MODERATE IRRITANT           

( ) = Total values not used for calculation of primary irritation index; Cf = crust formation; D = desquamation; Le = loss of skin elasticity

Table 2. Individual Daily and Mean Scores for Dermal Irritation following 4 -hour Exposure required for EU Labelling Regulations

Skin Reaction Skin ReactionReading (Hours) Individual Scores - Rabbit Number and Sex (Bodyweight kg)
10 Male
(2.75)
36 Male
(2.90)
78 Male
(2.88)
Erythema/Eschar Formation 24 2 2 2
48 2 2 2
72 1 1 2
Total   5 5 6
 Mean Score   1.7 1.7 2.0 +
Oedema Formation 24 2 2 2
48 2 2 2
72 1 1 2
Total   5 5 6
Mean Score   1.7 1.7 2.0 +

+ = positive criterion

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: EU-GHS
Conclusions:
According to Regulation (EC) No 1272/2008, the test material is not classified as skin irritant or corrosive. Mean values for erythema/eschar or for oedema from gradings at 24, 48 and 72 hours after patch removal amount up to 2 (under the cut-off value of 2.3).
Executive summary:

An OECD Guideline 404 study was performed to assess the irritancy potential of phosphoric acid, mono- and di-(C8 -C10) ester, compds. with C12 -14 amine to the skin of the New Zealand White rabbit in compliance with GLP. A single 4-hour, semi-occluded application of 0.5 mL of the test material to the intact skin of three rabbits (2 males / 1 female) produced well-defined erythema and slight to moderate oedema. Observations were performed 1 h, 24 h, 48 h, 72 h, 7 d and 14 d after application. Loss of skin elasticity, crust formation and slight desquamation were also noted. Treated skin sites appeared normal at the 14-day observation. The test material produced a primary irritation index of 3.3 and was classified as a moderate irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.