Sodium salts of Mono- and di-[reaction products of dodecyl alcohol and ethylene oxide]phosphates

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

From 28 February 2000 to 27 October 2003

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: The study is a screening test but followed international guidance requirements with acceptable restrictions.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

yes

Remarks:

: screening test/ 5 animals in the main test rather than 10, only one concentration tested, no certificate of analysis included

Principles of method if other than guideline:

Not applicable

GLP compliance:

no

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The GPMT study was already available before the substance had to be registered under Reach regulation.

Test material

Test material information

Constituent 1

Test material form:

other: Liquid at ambient temperature

Details on test material:

- Name of test material (as cited in study report): Dermalcare MAP L-213/K
- Physical state: clear liquid
- Stability under test conditions: assumed to be stable by the sponsor
- Storage condition of test material: ambient temperature

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

not specified

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Nossan S.r.l., Italy
- Age at study initiation: no data
- Weight at study initiation: approximately 626 g
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To: no data

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Induction (intradermal) : 0.1%
Induction (epicutaneous) : 60%
Challenge: 30%

Challenge

Challenge 1

Route:

other: epicutaneous

Vehicle:

water

Challenge 2

Concentration / amount:

Induction (intradermal) : 0.1%
Induction (epicutaneous) : 60%
Challenge: 30%

No. of animals per dose:

Preliminary test: 3 treated animal
Main study: 3 animals for the control group, 5 animals for the treated group

Details on study design:

RANGE FINDING TESTS: one animal was treated by an intradermal injection of different concentrations of test item (0.5-50%) and erythema was scored at the injection site 6 days after the intradermal injection. The test item was corrosive (necrosis) from the concentration of 0.5%. However the effects were lower at the lowest concentrations of 0.5 and 1%. Two additionnal animals were examined for skin irritation 24 and 48 hours after a topical application of the test item at different concentrations (5-60%). The test substance applied topically was not irritating whatever the tested concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: -
- Test groups: Test substance in Freund's Complete Adjuvant (FCA) emulsion and in water. Before the topical application, sodium Lauryl sulphate was applied on the skin to promote an irritant reaction.
- Control group: Test substance in water
- Site: no data
- Frequency of applications: intradermal injection, then one week later topical application
- Duration: 0-7 days
- Concentrations: intradermal 0.1%, topical 60%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 21
- Exposure period: -
- Test groups: Test substance in water
- Control group: Test substance in water
- Site: no data
- Concentrations: 30%
- Evaluation (hr after challenge): 24 and 48 hrs

Challenge controls:

There is no reference to a positive historical control substance.

Positive control substance(s):

not specified

Results and discussion

Positive control results:

no data

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

30%

No. with + reactions:

0

Total no. in group:

3

Clinical observations:

no data

Remarks on result:

no indication of skin sensitisation

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

30%

No. with + reactions:

0

Total no. in group:

3

Clinical observations:

no data

Remarks on result:

no indication of skin sensitisation

Results 3

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

30%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

one animal dead

Remarks on result:

no indication of skin sensitisation

Results 4

Key result

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

30%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

one animal dead

Remarks on result:

no indication of skin sensitisation

Any other information on results incl. tables

One animal in the treated group was found dead during the observation period (no more details are given in the study report).

Animals gained weight during the study period.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, Dermalcare MAP L-213/K is not a skin sensitiser in the guinea pig maximisation test.

Executive summary:

In a guinea pig maximisation test (screening study) performed similarly to the OECD No. 406 guideline, Dermalcare MAP L-213/K diluted in sterile water was tested for its skin sensitising potential in Dunkin-Hartley guinea pigs. A preliminary test on one animal allowed determining the appropriate concentrations of the test item for the induction and the challenge phases of the main study. Indeed, 6 days after an intradermal injection strong irritant skin effects were observed with signs of necrosis. Those effects were observed from concentrations of 0.5%. However at 0.5 and 1% the effects were decreased compared to the higher concentrations. The concentration of intradermal induction of 0.1% was therefore chosen for the main test. 24 and 48 hours after a topical application, the test item applied on the skin up to 60% induced no sign of irritation. Therefore the concentrations of 60% for the topical induction phase and of 30% for the challenge phase were chosen for the main test.

 

For the main test, 3 animals were treated only with the vehicle (water) (control group) and 5 animals were treated with the test substance.

For the induction phase, animals received an intradermal injection of the test substance at 0.1% in sterile water or in Freund’s Complete adjuvant (FCA) emulsion. One week later, a second induction was performed by a topical application of the test item at 10% in water. Before this topical induction, the skin was treated with Sodium Lauryl sulfphate to promote an irritant reaction.

Two weeks after the topical induction phase, challenge was performed by applying the test substance at 1% in water on the skin of guinea pigs. The observation of skin irritation 24 and 48 h after the challenge treatment informs on the skin sensitising potential of the test item.

 

No sign of skin sensitisation was observed 24 and 48 hrs after the challenge in any animals (control and treated groups). The body weight was recorded and no effect was observed.

 

Therefore, under the test conditions, Dermalcare MAP L-213/K is not considered as a skin sensitiser according to the criteria of Regulation (EC) 1272/2008 (CLP) and Directive 67/548/EEC.