Reaction mass of phenol and tetraphenylphosphonium phenolate

Endpoint summary

Description of key information

no skin sensitization effects observed in a GPMT

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:

2001

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

1992

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1996

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

1998

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

This study on skin sensitization was conducted in 2002, prior to current REACH requirements and testing strategies. It is considered adequate for evaluation of this toxicological endpoint.

Species:

guinea pig

Strain:

other: Hsd Poc:DH

Sex:

male

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH Laboratory Animal Breeders, 33176 Borchen, Germany
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 363-416 g
- Housing: 2-3 per cge
- Diet and Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 40-60
- Air changes (per hr): >= 10
- Photoperiod (hrs dark / hrs light): 12
- IN-LIFE DATES: From: 2001-07-31 To: 2001-08-24

Route:

intradermal

Vehicle:

polyethylene glycol

Remarks:

400

Concentration / amount:

5 % / 0.1 mL

Day(s)/duration:

single injection on day 1 of the study

Adequacy of induction:

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

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Remarks:

400

Concentration / amount:

25 % / 0.5 mL

Day(s)/duration:

single application on day 7 of the study

Adequacy of induction:

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

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Remarks:

400

Concentration / amount:

6 % / 0.5 mL

Day(s)/duration:

single 24h-treatment on day 21 of the study

Adequacy of challenge:

highest non-irritant concentration

No. of animals per dose:

10 animals in treatment group, 5 animals in control group

Details on study design:

RANGE FINDING TESTS:
for intradermal induction dose: one animal was given intradermal injections twice, in each case with 0.1 mL of the following test item concentrations: 0 %, 1 %, 2.5 %, and 5 %. At the 0 - 2.5 % injection sites white weal with red surronding appeared after 24 and 48 hours. At the 5 % injection site great white wheal with great red surrounding appeared after 24 and 48 hours.
for topical induction: Three different concentrations (6, 12, and 25 %) and the vehicle were tested in each case on four guinea pigs. The patches moistened with 0.5 mL of the test item formulations or the vehicle were applied to each animal under occlusive conditions for 24 hours. At the end of the exposure period, the remaining test item or the vehicle were removed with physiological saline solution and twenty-one hours later the treated areas were shorn. The skin reactions were evaluated 48 hours and 72 hours after the start of the application. No skin reactions were observed after treatment with 6 and 12 %. The test dose of 25 % led to slight to moderate skin reaction in one animal.
for challenge: One week prior to the challenge, the challenge concentration was determined on 2 guinea pigs in the main study that were treated in the same manner as the control animals during the inductions. Four patches each loaded with 0.5 mL test item formulation (3, 6, ans 12 %) or the vehicle were applied to each animal under occlusive conditions for 24 hours.The skin reactions were evaluated 48 hours and 72 hours after the start of the application.
No skin reactions were observed after treatment with 3 and 6 %. The test dose of 12% led to slight skin reaction in one animal.

MAIN STUDY
A. INDUCTION EXPOSURE
The dorsal region and the flanks of the guinea pigs were shorn one day prior to the application. Starting behind the nape of the neck, three injections each in a row were made on the left and the right side of the spinal column. The 1st and 2nd injections were made as contiguous as possible and the 2nd and 3rd injections in a distance of about 2 cm.
- No. of exposures: Three pairs of intradermal injections were made once into the shoulder region.
a) FCA (Freud's Complete Adjuvant) 0.1 mL, 1:1 diluted in physiological saline
b) Test substance formulation 0.1 mL
c) Test substance formulation including FCA 0.1 mL
- Exposure period: single injection
- Control group: The control group received the vehicle instead of the test substance formulation.
- Concentrations: test item: 5 %

Topical induction (Day 7)
- No. of exposures: single topical treatment
- Exposure period: 48 hours (occlusive conditions; the patch was tightly wrapped using aluminium foil and adhesive tape)
- Control group: The control group received the vehicle instead of the test substance formulation.
- Site: Topical applications were made between and on the injection sites
- Concentration: 0.5 mL of the 25 % test substance in PEG 400 were placed onto 2 x 4 cm hypoallergic patches and applied to the skin.
- Evaluation: The test sites were inspected after removal of the patches.

B. CHALLENGE EXPOSURE
- No. of exposures: single topical treatment
- Exposure period: 24 hours (occlusive conditions)
- Control group/Test group: The animals of test and control group received the vehicle on the right flank and the test substance formulation on the left flank.
- Site: Topical applications were made on right and left shoulder.
- Concentrations: 0.5 mL of the 6 % test substance in PEG 400 were applied to 2 x 2 cm pieces of hyperallergic patch in the same fashion as was used for topical induction and put on the left flank.
- Evaluation (hr after challenge): The test sites were inspected 24 and 48 hours after removal of the patches.

OTHER:

Challenge controls:

The animals of the control group were treated in the same manner as the animals of the test item group; however, the formulations for injection site pairs 2 and 3 did not contain any test item but in pair 2 undiluted vehicle and in pair 3 a 50 % formulation of the vehicle in a 1 : 1 mixture FCA/physiological saline solution.
For topical induction the animals were treated with 0.5 mL PEG 400 alone.
For challenge the control animals were treated the same way with the test substance as the treatment group.

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5 % for intradermal induction, 25 % for topical induction, 6 % for challenge

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

5 % for intradermal induction, 25 % for topical induction, 6 % for challenge

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

none

Remarks on result:

no indication of skin sensitisation

Reading:

other: 1st and 2nd reading

Group:

negative control

Dose level:

vehicle/FCA only for intradermal induction, vehicle only for topical induction, 6% for challenge

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: no skin effects

no treatment related effects on body weight; after intradermal induction the animals in the control and test item group showed wheal, white wheal with surrounding and encrustations. After 7 days only encrustations were seen. After patch removal of topical induction no skin effects in both groups were seen.

Interpretation of results:

GHS criteria not met

Executive summary:

A Guinea Pig Maximization Test (GPMT) following OECD 406 was performed to determine the skin sensitizing potential of the test substance in 10 female Guinea pigs and 5 control animals. The intradermal induction was performed using a 5 % test item concentration and the topical induction using a 15 % test item concentration. As vehicle PEG 400 was used. After intradermal induction the animals in the control and test group showed strong effects up to encrustation at the injection sites. The challenge using 6 % test item formulation led to no skin effects in the animals of the treatment and control group. By comparing the results in the treatment and control group under the conditions of this GPMT and with respect to the evaluation criteria the test item exhibits no skin sensitization potential.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

A Guinea Pig Maximization Test (GPMT) following OECD 406 was performed to determine the skin sensitizing potential of the test substance in 10 female Guinea pigs and 5 control animals. The intradermal induction was performed using a 5 % test item concentration and the topical induction using a 15 % test item concentration. As vehicle PEG 400 was used. After intradermal induction the animals in the control and test group showed strong effects up to encrustation at the injection sites. The challenge using 6 % test item formulation led to no skin effects in the animals of the treatment and control group. By comparing the results in the treatment and control group under the conditions of this GPMT and with respect to the evaluation criteria the test item exhibits no skin sensitization potential.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

According to the results of a Guinea Pig Maximization Test with the test substance no classification is warranted for skin sensitization.