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

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

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

Qualifier:

according to guideline

Guideline:

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

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)

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

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)

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

Key result

Parameter:

SI

Value:

0.78

Test group / Remarks:

5%

Key result

Parameter:

SI

Value:

0.8

Test group / Remarks:

10%

Key result

Parameter:

SI

Value:

0.58

Test group / Remarks:

505

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A study was performed to assess the skin sensitisation potential of the substance following topical application of a suspension of MPP in acetone/olive oil 4:1 at concentrations of 25%, 10% or 5% w/w to the dorsal surface of the ear of the mouse. The stimulation index was found to be less than three for all animals at all tested concentrations and therefore MPP is considered to be a non-sensitiser.

Migrated from Short description of key information:

MPP is unlikely to be a skin sensitiser based on a Local Lymph Node Assay test in mice.

Justification for selection of skin sensitisation endpoint:

A well conducted study performed under GLP in accordance with a recognised guideline.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

A stimulation index of less than 3 was recorded for three concentrations of the test material (0.78, 0.8 and 0.58 for 25%, 10 % and 5% w/w, respectively). According to the classification criteria in section 3.4.2.2.3.1 a stimulation index of less than three is regarded as a negative result and therefore MPP can be considered to be not classified for skin sensitisation.