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Diss Factsheets

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
from December 20th 1994 to February 11th, 1995
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
GLP guideline study with some restrictions: no certificate of analysis

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report date:
1995

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no certificate of analysis
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA method is available

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2,4,4-trimethylpentyl)phosphinic acid
EC Number:
280-445-7
EC Name:
Bis(2,4,4-trimethylpentyl)phosphinic acid
Cas Number:
83411-71-6
Molecular formula:
C16H35O2P
IUPAC Name:
bis(2,4,4-trimethylpentyl)phosphinic acid
Test material form:
liquid

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 290-341g
- Housing: housed in groups of five in suspended metal cages with wire mesh floors
- Diet (e.g. ad libitum): A vitamin C enriched guinea-pig diet FD2, ad libitum
- Water (e.g. ad libitum): drinking water, ad libitum
- Acclimation period: yes, for 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 °C
- Humidity (%): 30-70 %
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: To: no data

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
coconut oil
Remarks:
Alembicol D
Concentration / amount:
induction:
intradermal: 0.25%
topical: 100%
challenge: 25, 50 and 100%
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
coconut oil
Remarks:
Alembicol D
Concentration / amount:
induction:
intradermal: 0.25%
topical: 100%
challenge: 25, 50 and 100%
No. of animals per dose:
20 test animals, 10 control animals
Details on study design:
RANGE FINDING TESTS: 8 concentrations (between 0.1 and 10%) were tested on 2 animals by intradermal injection to study the skin irritation potential. Concentrations higher than 0.25 % caused severe skin reactions such as necrosis. 0.25 % was chosen as the intradermal induction concentration as it caused skin irritation without adverse effect in tested animals. Four concentrations (between 30 and 100%) were tested in 4 animals by topical application. The test item was not irritating at any concentrations.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 1 intradermal injection, 1 topical application
- Exposure period: topical application for 48h
- Test groups: FCA or TS in vehicle or TS in a 50:50 miwture of FCA and vehicle
- Control group: FCA, or vehicle or mixture of FCA and vehicle
- Site: 40 x 60 mm area of dorsal region on the scapular region (20 x 40 mm patch)
- Frequency of applications: -
- Duration: 0-7 days
- Concentrations:intradermal: 0.25 %, topical: 100 %

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: day 21 and day 28
- Exposure period: 24h
- Test groups: TS in vehicle
- Control group: TS in vehicle
- Site: left site of the flank (20 x 20 mm area)
- Concentrations: first challenge (d21): 50 and 100%; second challenge (d28): 25 and 50%
- Evaluation (hr after challenge): 24, 48, 72 hours after the removal of the patches

OTHER: during the induction period, on day 6, 0.2 ml of 10 % SLS in petrolatum was applied before the topical application of TS in order to induce a skin irritation reaction.
Challenge controls:
10 animals, same challenge treatment as the tested groups (50% and 100% TS)
Positive control substance(s):
no
Remarks:
HCA (the positive control is checked periodically at HRC)

Results and discussion

Positive control results:
the historical results of different tests performed with HCA between end of December 1992 and October 1994 were adequate.

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
50% and 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Signs of dermal reaction such as dryness, thickening and sloughing of the epidermis. However, those effect are also observed in the control group at the same intensity.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 50% and 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Signs of dermal reaction such as dryness, thickening and sloughing of the epidermis. However, those effect are also observed in the control group at the same intensity..
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50 and 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Signs of dermal reaction such as dryness, thickening and sloughing of the epidermis. However, those effect are also observed in the control group at the same intensity.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 50 and 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Signs of dermal reaction such as dryness, thickening and sloughing of the epidermis. However, those effect are also observed in the control group at the same intensity..
Reading:
other: 3rd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
50 and 100%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Signs of dermal reaction such as dryness, thickening and sloughing of the epidermis. However, those effect are also observed in the control group at the same intensity.
Remarks on result:
other: .
Remarks:
Reading: other: 3rd reading. . Hours after challenge: 72.0. Group: test group. Dose level: 50 and 100%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: Signs of dermal reaction such as dryness, thickening and sloughing of the epidermis. However, those effect are also observed in the control group at the same intensity.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
25 and 50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no signs of skin irritation
Remarks on result:
other: Reading: rechallenge. Hours after challenge: 24.0. Group: test group. Dose level: 25 and 50%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no signs of skin irritation.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
25 and 50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no signs of skin irritation
Remarks on result:
other: Reading: rechallenge. Hours after challenge: 48.0. Group: test group. Dose level: 25 and 50%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no signs of skin irritation.
Reading:
rechallenge
Hours after challenge:
72
Group:
test chemical
Dose level:
25 and 50%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no signs of skin irritation
Remarks on result:
other: Reading: rechallenge. Hours after challenge: 72.0. Group: test group. Dose level: 25 and 50%. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no signs of skin irritation.

Applicant's summary and conclusion

Interpretation of results:
other: not classified as a skin sensitiser according to the CLP Regulation (EC) No.1272/2008
Conclusions:
Non-skin sensitiser
Executive summary:

In a guinea-pig maximisation test performed according to the OECD 406 Guideline and in compliance with the GLP, twenty male Dunkin/Hartley guinea-pigs were tested to assess the skin sensitisation potential of the test material.

In a preliminary study, different concentrations of the test substance were tested in order to determine the concentrations of the test substance that would produce irritation suitable for the induction phase of the main study and the maximum non-irritant concentration by the topical route of administration for the challenge phase of the main test.

In the main study, the animals received on day 1, an intradermal injection of the test substance diluted at 0.25 % in Alembicol D (coconut oil). Freund Complete Adjuvant (FCA) was also added to the mixture to potentiate the skin sensitisation. The control group was treated in the same condition with Alembicol D and FCA only. Six days after the intradermal induction, all animals (treated and control group) were treated with Sodium Lauryl Sulphate at 10 % in petrolatum. One day after (day 7), a topical application during 24h under occlusive patch conditions of undiluted (100 %, non irritant concentration) test substance was performed at the same site (dorsal region) in the treated group animals and a topical application of vehicle only was performed in the control group animals.

The first challenge test was conducted 2 weeks after the topical induction by applying the test substance on a different site (flank) at two different concentrations: 50 and 100 %. A second challenge test was conducted one week later (day 28) with lower concentrations (25 and 50 %). The challenge applications were performed under occlusive condition for 24h and the dermal reaction was assessed 24, 48 and 72 hours after the patch removal.

No signs of ill health or toxicity were recorded. During the induction exposure, dermal reactions were observed: necrosis after the intradermal injection of FCA and of test substance in FCA, and slight erythema after the topical application in the treated and control group. At the first challenge, dermal reactions were seen on both the control and test animals. Whilst the reactions seen for test animals were generally not more severe than those seen for the controls, the irritation seen for the control animals was considered to make precise evaluation of the test response difficult. A second challenge application was therefore carried out, one week later using lower concentrations of the test substance. At the second challenge application, there were no dermal reactions seen in any of the test or control animals.

Therefore, under the test conditions, the substance is not considered to be a skin sensitiser.