Alcohols, C18-unsatd and ethoxylated C18-unsatd., phosphates (5 moles ethoxylation)

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

2004

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: Internal Human repeat insult patch test (HRIPT) Protocol No. 1.01 (at CPTC)

Deviations:

not specified

Principles of method if other than guideline:

A Human Repeated Insult Patch Test (HRIPT) was conducted to determine the skin sensitivity potential of the test substance, following epicutaneous induction with 10% test substance concentrations (in distilled water; pH 6.49) to 48 healthy volunteers for 1 to 4 d under a semi-occlusive conditions. After a rest period of ca. 2 weeks, the substance was applied under the same conditions to a new site as a challenge followed by reading the sites for immediate and delayed responses after 24 and 72 h.

GLP compliance:

not specified

Type of study:

patch test

Justification for non-LLNA method:

- Human study

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C18-unsatd and ethoxylated C18-unsatd., phosphates (5 moles ethoxylation)

Molecular formula:

C18H37O4P (representative of phosphate monoesters; i.e., mono- C18-unsatd. PSE) C28H57O9P1 (representative of ethoxylated phosphate monoesters; i.e., mono- C18-unsatd. AE5 PSE) C36H71O4P1 (representative of phosphate diesters; i.e., di- C18-unsatd. PSE) C46H91O8P1 (representative ethoxylated phosphate diesters; di- C18-unsatd. PSE and C18-unsatd. AE5 PSE) C82H161O21P1 (representative ethoxylated phosphate diesters; di- C18-unsatd. AE5 PSE)

IUPAC Name:

Alcohols, C18-unsatd and ethoxylated C18-unsatd., phosphates (5 moles ethoxylation)

Test material form:

liquid

In vivo test system

Test animals

Species:

other: Human

Sex:

male/female

Details on test animals and environmental conditions:

48 healthy volunteers

Study design: in vivo (non-LLNA)

Induction

Route:

epicutaneous, semiocclusive

Vehicle:

water

Concentration / amount:

10%

Day(s)/duration:

1 - 4 d

Adequacy of induction:

not specified

Challenge

Route:

epicutaneous, semiocclusive

Vehicle:

water

Concentration / amount:

10%

Day(s)/duration:

1

Adequacy of challenge:

other: two weeks after last induction

No. of animals per dose:

48

Challenge controls:

-

Positive control substance(s):

no

Results and discussion

Positive control results:

-

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

10% in water

No. with + reactions:

0

Total no. in group:

48

Clinical observations:

none

Remarks on result:

other: see 'Any other information on results incl. tables'

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

10% in water

No. with + reactions:

1

Total no. in group:

48

Clinical observations:

none

Remarks on result:

other: see 'Any other information on results incl. tables'

Results 3

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

not tested

Clinical observations:

not tested

Remarks on result:

not measured/tested

Results 4

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

not tested

Clinical observations:

not tested

Remarks on result:

not measured/tested

Any other information on results incl. tables

Results: details

- Subject #12 developed moderate erythema and mild edema during Days 1 and 2 of induction. Patching was continued on Day 3. Subject #12 had a barely perceptible response. While on Day 4 it was noted that Subject #12 had mild erythema covering the patch site. Two weeks later subject #12 was challenged with the the test substance and there was no response indicating that the initial response was not clinically relevant.

 - Subject # 13 developed spotty erythema on Days 2, 3, and 7. Two weeks later subject #13 was challenged and 24 h later they developed moderate erythema and mild edema. By 72 h post-challenge only spotty erythema was noted (Subject # 13). This pattern of skin reactivity is suggestive of a pre-existing hypersensitivity. No evidence of induced allergic contact sensitization was recorded.

Applicant's summary and conclusion

Interpretation of results:

other: not classified based on EU CLP criteria

Conclusions:

Under the study conditions, the test substance was determined to be non-sensitiser to the skin (Croda, 2004). % in distilled/deionised water pH 6.49)

Executive summary:

A study was conducted to determine the skin sensitivity potential of the test substance, ‘mono- and di- C18-unsatd. PSE and C18-unsatd. AE5 PSE’, according to the Human Repeated Insult Patch Test (HRIPT). In the induction phase, a 10% test substance preparation (in distilled water; pH 6.49) was applied epicutaneously to 48 healthy volunteers for 1 to 4 d under a semi-occlusive conditions. After a rest period of ca. 2 weeks, the substance was applied under the same conditions to a new site as a challenge. At the end of 24 h, the occluded patch was removed and the site was read for immediate response. Follow-up readings were made 72 h after challenge. Subject #12 developed moderate erythema and mild edema during Day 1 and 2 of induction, barely perceptible response on Day 3 and mild erythema on Day 4. However, two weeks later the subject #12 was challenged with the test substance and there was no response indicating that the initial response was not clinically relevant. Subject # 13 developed spotty erythema on Days 2, 3, and 7. Two weeks later subject #13 was challenged and 24 h later they developed moderate erythema and mild edema. By 72 h post-challenge only spotty erythema was noted (Subject # 13). This pattern of skin reactivity is suggestive of a pre-existing hypersensitivity. No evidence of induced allergic contact sensitisation was recorded in any other volunteers. Under the study conditions, the test substance did not indicate a potential for dermal irritation or allergic contact sensitization in human volunteers at 10% test concentrations (Croda, 2004).