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Description of key information

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:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
adopted July 22nd, 2010
Qualifier:
according to
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Version / remarks:
adopted May 30th, 2008
GLP compliance:
yes (incl. certificate)
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: Pretest: Charles River, UK; Main Experiment: Harlan Lab. B.V., Netherlands
- Age at study initiation: Pretest: 9-10 weeks, main experiment: 8-9 weeks
- Weight at study initiation: 18.6 - 22.5g
- Housing: groups in makrolon type II or III cages
- Diet (e.g. ad libitum): pelleted standard diet ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/-2°C
- Humidity (%): 31-65%
- Photoperiod (hrs dark / hrs light): 12h/12h

Vehicle:
acetone/olive oil (4:1 v/v)
Concentration:
10%, 25%, 50% (w/w) (verified analytically)
No. of animals per dose:
5 (2 in the range finding test)
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: maximal achieveable concentration: 50%
- Irritation: 50%: erythema grade 1, slight ear swelling and an increase in ear thickness (33.3%), which was not observed anymore on day 6
25%: No signs of irritation or systemic toxicity were observed

MAIN STUDY
- Criteria used to consider a positive response:
1. at least one concentration of the test item, showing no excessive local irritation, results in an incorporation of ³HTdR ad least 3-fold greater than that recorded in control mice (indicated by the SI)
2. data are compatible with a conventional dose reponse, although allowance must be made (especially at high topical concentrations) for either local toxicity or immunological suppression.

TREATMENT PREPARATION AND ADMINISTRATION:
Sonicating and warming to 37°C was used for formulate the test item. Preparations were freshly made before dosing.
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Parameter:
SI
Value:
2.22
Test group / Remarks:
10%
Parameter:
SI
Value:
2.96
Test group / Remarks:
25%
Parameter:
SI
Value:
3.45
Test group / Remarks:
50%
Parameter:
EC3
Value:
792.1
Parameter:
other: Disintegrations per minute
Value:
792.1
Test group / Remarks:
Control
Parameter:
other: Disintegrations per minute
Value:
1 757.5
Test group / Remarks:
10%
Parameter:
other: Disintegrations per minute
Value:
2 347.1
Test group / Remarks:
25%
Parameter:
other: Disintegrations per minute
Value:
2 742.3
Test group / Remarks:
50%
Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
The test substance was found to be a sensitizer, the EC3 value was calculated to be 27%.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

In a local lymph node assay (LLNA) accoring to OECD 429 and GLP, 10%, 25%, and 50% of diphenyl(2,4,6 -trimethylbenzoyl)phosphine oxide in acetone olive oil (4:1 v/v) were topically applied to the dorsal part of the ears of 5 CBA mice per group. The animals did not show any signs of systemic toxicity or local skin irritation during the course of the study and no cases of mortality were observed. A statistically significant or biologically relevant increase in ear weights was not observed in any treated group in comparison to the vehicle control group. Furthermore, the cutoff-value for a positive response regarding the ear weight index of 1.1 reported for BALB/c mice (see Ref. 9) was not exceeded in any dose group.

In this study Stimulation Indices (S.I.) of 2.22, 2.96, and 3.46 were determined with the test item at concentrations of 10, 25, and 50% (w/w) in acetone:olive oil (4+1 v/v), respectively. A clear dose response was observed. Based on the S.I.’s obtained with 25 and 50% test item concentration, an EC3 value of 27.0% (w/w) was calculated. A statistically significant increase in DPM value and also in lymph node weight was observed in all dose groups in comparison to the vehicle control group (p<0.05). A statistically significant and biologically relevant increase in lymph node cell count was observed in the mid (25%) and high (50%) dose group in comparison to the vehicle control group (p<0.05). Furthermore, the cutoff-value for a positive response regarding the lymph node cell count index of 1.55 reported for BALB/c mice was exceeded in the mid and high dose group (indices of 1.91 and 1.83, respectively).


Migrated from Short description of key information:
LLNA: sensitzing (BASF 2012, according to OECD429 and GLP)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In the LLNA diphenyl(2,4,6-trimethylbenzoyl)phosphine oxide was demonstrated to be a skin sensitizer due to a dose dependent increase in lymphocyte proliferation and a calculated EC3 of 27%. Thus it has to be classified as R43 according to EU criteria and as skin sensitizing category 1B accoring to CLP/GHS-EU.

There are no data available to for classification of diphenyl(2,4,6 -trimethylbenzoyl)phosphine oxide as a sensitizer of the respiratory tract.