Diphosphoric acid, compound with 1,3,5-triazine-2,4,6-triamine

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

21 March 2005 to 20 April 2005

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted in accordance with an internationally recognised method

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Diphosphoric acid, compound with 1,3,5-triazine-2,4,6-triamine

EC Number:

239-590-1

EC Name:

Diphosphoric acid, compound with 1,3,5-triazine-2,4,6-triamine

Cas Number:

15541-60-3

Molecular formula:

C3H6N6.xH4O7P2

IUPAC Name:

diphosphoric acid, compound with 1,3,5-triazine-2,4,6-triamine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): MPP
- Appearance: white powder
- Analytical purity: 98.9%
- Lot/batch No.: 10184
- Storage conditions: room temperature in the dark

In vivo test system

Test animals

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: reputable laboratory animal supplier
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 15 - 23g
- Housing: suspended solid-floor polypropylene cages furnished with softwood woodflakes.
- Diet: certified rat and mouse food. ad libitum
- Water: mains tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): approximately 15 per hour
- Photoperiod (hrs dark / hrs light): 12 hours light / 12 hours dark

IN-LIFE DATES: From: To: 21 March 13 April 2005

Study design: in vivo (LLNA)

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

Preliminary test: 25% w/w
Main test: 5, 10 and 25% w/w

No. of animals per dose:

4

Details on study design:

RANGE FINDING TESTS:
- Compound solubility: the maximum concentration that could be formulated in any solvent was 25% w/w. The substance was soluble at this level in the preferred solvent, 4:1 acetone/olive oil
- Irritation: observations for any irritancy were made, as well as for signs of systemic toxicity, clinical signs, bodyweight and mortality
- Lymph node proliferation response: not performed

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Local Lymph Node assay
- Criteria used to consider a positive response: a test item is regarded as a sensitiser in the LLNA if the exposure to one or more test concentrations results in a 3-fold or greater increase in incorporation of 3HTdR compared with concurrent controls, as indicated by the Stimulation Index (S.I.).

TREATMENT PREPARATION AND ADMINISTRATION:

The test material was freshly prepared in acetone/olive oil 4:1. This vehicle was chosen as it produced the highest concentration that was suitable for dosing.

Each of four animals, were treated with 50 µl (25 µl per ear) of the test material as a suspension in acetone/olive oil 4:1 at concentrations of 25%, 10% or 5% w/w. A further group of four animals was treated with acetone/olive oil 4:1 alone.

Positive control substance(s):

hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:

Formulated in cottonseed oil:
10% v/v SI index, 1.52, negative
25% v/v SI index, 2.63, negative
50% v/v SI index, 5.07, positive

Conclusion: hexylcinnamaldehyde is a sensitiser under the conditions of the test

In vivo (LLNA)

Results

Results 1

Key result

Parameter:

SI

Value:

0.78

Test group / Remarks:

5%

Results 2

Key result

Parameter:

SI

Value:

0.8

Test group / Remarks:

10%

Results 3

Key result

Parameter:

SI

Value:

0.58

Test group / Remarks:

505

Any other information on results incl. tables

Preliminary test

No signs of systemic toxicity were observed and therefore the main test was conducted at dose levels of 5, 10 and 25% w/w.

Main test

A stimulation index of less than 3 was recorded for the three concentrations of the test material (25%, 10 % and 5% w/w).

There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test.

Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material was considered to be a non-sensitiser under the conditions of the test.