Reaction mass of hexadecyl dihydrogen phosphate and dihexadecyl hydrogen phosphate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Feb - Apr 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP conform guideline study with sufficient reporting

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

Hexadecyl dihydrogen phosphate

EC Number:

222-581-1

EC Name:

Hexadecyl dihydrogen phosphate

Cas Number:

3539-43-3

Molecular formula:

C16H35O4P

IUPAC Name:

hexadecyl dihydrogen phosphate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

In vivo test system

Test animals

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England
- Weight at study initiation: 400 -450 g
- Housing: in suspended cages with wire mesh floors
- Diet (e.g. ad libitum): Vitamin C enriched Guinea-pig Diet F.D.1., ad libitum; hay was given weekly
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 12 days

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

IN-LIFE DATES: From: 28.2. To: 1.4.1989

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

water

Induction 2

Concentration / amount:

Induction(intradermal):
0.5% (w/w)

Induction (topical):
40% (w/w)

1. Challenge:
40 and 20% (w/w)

2. Challenge:
10 and 1% (w/w)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

water

Challenge 2

Concentration / amount:

Induction(intradermal):
0.5% (w/w)

Induction (topical):
40% (w/w)

1. Challenge:
40 and 20% (w/w)

2. Challenge:
10 and 1% (w/w)

No. of animals per dose:

Control animals: 10
Test animals: 20

Details on study design:

Induction phase:
- Intradermal injections
A 4x6 cm area of dorsal skin on the scapular region of the guinea-pig was clipped free. Three pairs of intradermal injections were made simultaneously.
Injections were prepared as follows:
1. Freund´s complete adjuvant was diluted with an equal volume of water for irrigation
2. Test item, 0.5% (w/w) in water for irrigation
3. Test item, 0.5% (w/w) in a 50:50 mixture of Freund´s complete adjuvant and water for irrigation

- Topical application
One week after the injections, the same 4x6 cm interscapular area was clipped and shaved free of hair. A 2x4 cm patch of Whatman No. 3 paper was saturated with the test item, 40% (w/w) in distilled water. The patch was placed on the skin and covered by length of impermeable plastic adhesive tape. This in turn was firmly secured by elastic adhesive bandage wound round the torso of the animal and fixed with "Sleek" impervious plastic adhesive tape. The dressing was left in place for 48 hours.

Control animals:
During the induction phase, the control animals were treated similarly to the test animlas with the exception that the test compound was omitted from the intradermal injections and topical applications.

Challenge phase:
The test and control animals were challenged topically two weeks after the induction period using the test item, 40% and 20% (w/w) in distilled water. Hair was removed by clipping and then shaving from an area on the left flank of each Guinea pig. A 2x2 cm patch of Whatman No. 3 paper was saturated with approx. 0.2 mL of the test item, 4% (w/w) in distilled water and applied to an anterior site on the flank. The test substance, 20% (w/w) in distilled water was applied in a similar manner to a posterior site. The patches were sealed to the flank 24 h under strips of "Blenderm" covered by "Elastoplast" wound round the trunk and secured with "Sleek".
Slight dermal reactions were observed in both test and control animals, therefore a second challenge application was made one week later using lower concentrations. The method employed was similar to that described above, with the exception that this occation the test item, 10% and 1% (w/w) in distilled water was applied to the right flank of all the test and control animals.

Challenge controls:

The sensitivity of the Guinea pig strain is checked periodically with Formalin.

Positive control substance(s):

yes

Remarks:

Formalin

Results and discussion

Positive control results:

Formalin (0.1 % intradermal; 10 % epidermal applied)
- incidence after challenge: 10 of 10 animals positive

In vivo (non-LLNA)

Results

Results 1

Reading:

rechallenge

Hours after challenge:

24

Group:

negative control

Dose level:

1% (anterior site); 10% (posterior site)

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

no effects reported

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: negative control. Dose level: 1% (anterior site); 10% (posterior site). No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: no effects reported.

Results 2

Reading:

rechallenge

Hours after challenge:

24

Group:

test chemical

Dose level:

1% (anterior site), 10% posterior site

No. with + reactions:

0

Total no. in group:

20

Clinical observations:

no effects reported

Remarks on result:

other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. Dose level: 1% (anterior site), 10% posterior site. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no effects reported.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

In this Guinea pig maximisation test (according to Magnusson and Kligman) performed in 20 albino Guinea pigs Hexadecyl dihydrogen phosphate did not produce evidence of delayed contact hypersensitivity.

Executive summary:

Testing for sensitising properties of Hexadecyl dihydrogen phosphate was performed in female guinea pigs according to the Guinea pig Maximisation Test. Intradermal induction was performed using 0.5 % Hexadecyl dihydrogen phosphate and the topical induction was conducted using 40% of the test item. The first challenge was carried out with 20% and 40% Hexadecyl dihydrogen phosphate (topical). Slight reactions were observed in both test and control animals. Therefore, one week after the first challenge and the second challenge was conducted with 1% and 10% test item.

There were no dermal reactions seen in any of the test or control animals following the second challenge application.

Hexadecyl dihydrogen phosphate is not a skin sensitiser.