Registration Dossier

Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 June 2010 - 7 July 2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to official EC and OECD test guidelines, and in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report Date:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
GLP compliance:
yes (incl. certificate)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Ferrophosphorus (Fe3P)
- Substance type: inorganic
- Physical state: solid
- Analytical purity: Iron: 82.7%
Phosphorus: 15.7%
- Lot/batch No.: 1068487
- Expiration date of the lot/batch: 15 February 2011
- Storage condition of test material: Room temperature

In vivo test system

Test animals

Species:
mouse
Strain:
other: CBA/Ca
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: UK
- Age at study initiation: Eight to twelve weeks
- Weight at study initiation: 16.8 to 20.8 g
- Housing: Animals were housed individually in polycarbonate cages with woodflake bedding. The mice were also given Nestlets and a plastic shelter for environmental enrichment. Each animal was assigned an alpha-numeric code and identified uniquely within the study by tail marking. Each cage label was colour-coded and was identified uniquely with the study number, dose level and animal mark.
- Diet (e.g. ad libitum):The animals had access to a standard rodent diet. This diet contained no added antibiotic or other chemotherapeutic or prophylactic agent.
- Water (e.g. ad libitum): Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12 hours continuous light and 12 hours continuous dark per 24 hours.


Study design: in vivo (LLNA)

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
0, 25, 50 and 100% w/v
No. of animals per dose:
4
Details on study design:
MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: The local lymph node assay
- Criteria used to consider a positive response: The test substance is regarded as a sensitizer if at least one concentration of the chemical results in a three-fold greater increase in 3HTdR incorporation compared to control values.

TREATMENT PREPARATION AND ADMINISTRATION: The mice were treated by daily application of 25 μl of each of one of these three concentrations, or control, to the dorsal surface of both ears for three consecutive days.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
This positive control study is considered to be valid if the results from the hexyl cinnamic aldehyde (HCA) group have a three-fold greater increase in 3HTdR incorporation compared to control values.
In this assay the test/control ratios obtained for HCA at 10, 25 and 50% v/v were 2.3, 7.7 and 13.1. This indicates that Hexyl cinnamic aldehyde demonstrates the potential to induce skin sensitization (delayed contact hypersensitivity) and confirms the sensitivity.

In vivo (LLNA)

Resultsopen allclose all
Parameter:
SI
Remarks on result:
other: Test / control ratios: Group 2 (25%w/v) = 0.7 Group 3 (50% w/v) = 0.5 Group 4 (100% w/v) = 0.8
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: see Remark
Remarks:
Group no: Concentration (% w/v) dpm 1 AOO 4786.95 2 25 3565.65 3 50 2594.25 4 100 3968.35 dpm Disintegrations per minute (less background count of 44.15 dpm) AOO Acetone:olive oil (4:1 v/v) (vehicle control)

Any other information on results incl. tables

There were no deaths and no signs of ill health or toxicity observed during this study, however the following observations were noted:

Greasy fur was noted for all control and test animals post-dose from Day 1 for control animals and from Day 3 for all test animals. This sign had resolved completely in all animals by Day 5.

Black dose residue on ears was noted for all test animals post-dose on Day 1. Wet fur was also noted for all test animals post-dose on Day 1. These signs had resolved completely in all animals by Day 4.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Ferrophosphorus (Fe3P) is not regarded as a potential skin sensitizer.