Triphenylphosphine

Endpoint summary

Description of key information

The test substance was sensitizing in a Guinea pig maximisation test.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jan - Feb 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

updated version November 1989

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

The study was performed in 1991, before the LLNA OECD TG 429 was in place (adopted in 2002).

Specific details on test material used for the study:

- Purity: 99.7%.

SOURCE OF TEST MATERIAL
- Lot/batch No.of test material: 65-2758.

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature.
- Stability under test conditions: Room temperature.
- Solubility and stability of the test substance in the solvent/vehicle: The test substance is stable in the carrier (Olive oil DAB 9) during 4 h . After 5 days the concentration found is significantly lower than the expected one, so that stability of test substance in the carrier can not be stated.

FORM AS APPLIED IN THE TEST (if different from that of starting material): in olive oil DAB 9

Species:

guinea pig

Strain:

Pirbright-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Lippische Versuchstierzucht, Hagemann GmbH & Co . KG, 0-W4923 Extertal 1, FRG.
- Females (if applicable) nulliparous and non-pregnant: not specified.
- Weight at study initiation: 282 - 337 g.
- Housing: Makrolon, type IV in fully air-conditioned rooms in which a central air-conditioning.
- Identification of the animals: Ear tag numbering.
- No. of animals per cage: 5.
- Diet: ad libitum.
- Water: ad libitum.
- Acclimation period: At least 7 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24°C.
- Humidity (%): 30 - 70%.
- Photoperiod (hrs dark / hrs light): 12 h light (6.00 - 18.00 hours) / 12 h darkness (18.00 - 6.00 hours)..
- IN-LIFE DATES: From: To:

Route:

intradermal and epicutaneous

Vehicle:

other: olive oil DAB 9

Concentration / amount:

intradermal induction: 5%,
epicutaneous induction: 10%.

Day(s)/duration:

intradermal induction: day 0, epicutaneous induction: day 6-8.

Adequacy of induction:

highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: olive oil DAB 9

Concentration / amount:

5%

Day(s)/duration:

day 20-21

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

Number of animals per control group: 5
Number of animals of the test group: 10

Details on study design:

RANGE FINDING TESTS: yes, dose selection from pretest results. The minimum irritant concentration was determined to be 10 % TPP in olive oil, the maximum non-irritant concentration 5 % in the vehicle (after 2x epicutaneous dosing of 24 h each). The following doses were selected: For intradermal induction 5% TPP in olive oil or in Freund's adjuvant solution. For percutaneous induction 10% TPP in olive oil. For challenge 5% TPP in olive oil.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2.
- Exposure period: intradermal injection, 48 h epicutaneous induction carried out 1 week after intradermal induction.
- Test groups: 1.
- Control group: 2.
- Site: shoulder.
- Frequency of applications: one intradermal and epicutanous each.
- Duration: 48 h epicutanous induction.
- Concentrations: intradermal 5%, epicutaneous 10%.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20-21.
- Exposure period: 24 h.
- Test groups: 1.
- Control groups: 2.
- Site: flank.
- Concentrations: 5%.
- Evaluation (hr after challenge): readings 14h and 48h after removal of the patch.

Challenge controls:

yes

Positive control substance(s):

yes

Remarks:

1-chlor-2,4-dinitro-benzol

Positive control results:

Under the test conditions chosen 1-chlor-2,4-dinitro-benzol had a sensitizing effect on the skin of the guinea pig strain used.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5% in olive oil DAB 9

No. with + reactions:

8

Total no. in group:

10

Clinical observations:

well-defined erythema in 2/10, very slight erythema in 6/10 animals

Remarks on result:

positive indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

5%

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

no skin reactions.

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

1%

No. with + reactions:

10

Total no. in group:

10

Clinical observations:

severe erythema and distinct edema in 1/10, severe erythema and slight edema in 4/10, distinct erythema in 5/10.

Remarks on result:

positive indication of skin sensitisation

Table 1: Number of animals with skin findings after the challenge (21 days after intradermal induction) with the test substance

	Challenge
	5% in olive oil DAB 9	olive oil DAB 9
Control group 1	0/5	0/5
Control group 2*	no application of test substance	1/5
Test group	8/10	0/10

Table 2: Number of animals with skin findings after the challenge (21 days after intradermal induction) with the positive control substance 1-chlor-2,4-dinitro-benzol

	Challenge
	1% in ethanol	ethanol conc
Control group 1	0/5	0/5
Control group 2*	no application of test substance	0/5
Test group	10/10	0/10

x/y : number of positive reactions/number of animals tested ; readings 24 h after the removal of the patch

* : Control group 2 that had been intended for a potential. 2nd challenge-was not-needed, since a 2nd challenge was not necessary on the basis of the unambiguous results of the 1st challenge.

Interpretation of results:

Category 1B (indication of skin sensitising potential) based on GHS criteria

Conclusions:

Under the test conditions chosen and following the described results the test substance has a sensitizing effect on the skin of the guinea pig.

Executive summary:

The test substance was tested for its sensitizing effect on the skin of the guinea pig in the maximization test based on the method of Magnusson and Kligman.

After intradermal induction well-defined erythema and slight edema were observed at the injection sites of the control and test animals at which only Freund's adjuvant/0.9% aqueous NaCl solution (1:1) was applied. Injection of test substance-preparation in olive oil DAB 9 resp. in-Freund'-s adjuvant/0.9% aqueous NaCl solution (1:1) caused well-defined erythema and slight edema in the test animals. The control animals injected with olive oil DAB 9 (vehicle) showed well-defined erythema.

After percutaneous induction incrustation, partially open (caused by the intradermal induction) in addition to well-defined erythema and slight edema could be observed in the test animals. The control animals which were applied with olive oil DAB 9 (vehicle) exhibited well-defined erythema and slight edema.

The percutaneous challenge (24 hours after the removal of the patch) with the 5% test substance preparation in olive oil DAB 9 caused well-defined erythema in 2 out of 10 test animals. Very slight erythema could be observed in 6 out of 10 test animals.

Olive oil DAB 9 applied as a vehicle caused very slight erythema in 1 out of 5 animals of control group 2. The animals of the test group and of control group 1 did not show any skin reactions.

Under the test conditions chosen and following the described results the test substance has a sensitizing effect on the skin of the guinea pig.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

The test substance was a skin sensitizer in a guinea pig maximization test performed according to Directive 84/449/EEC, B.6.

After challenge with a 5% solution of the test substance, 8 of 10 animals exhibited very slight to well-defined erythema, while no animals in the control group showed a response (BASF, 1991).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. As a result the substance is considered to be classified for skin sensitization Cat. 1B under Regulation (EC) No. 1272/2008, as amended for the tenth time in Regulation (EU) No 2017/776.