Phenethyl pivalate

Endpoint summary

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:

1973

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Non-GLP study meets generally accepted scientific principles, acceptable for assessment with restrictions: only 8 animals in each test group; no data about the purity and no certificate of analysis of the test substance; no information on the strain, age, sex, body weight, source and housing conditions of the animals; individual animal data was not reported

Reason / purpose for cross-reference:

reference to same study

Reason / purpose for cross-reference:

reference to other study

Principles of method if other than guideline:

Method: Open epicutaneous test

GLP compliance:

no

Remarks:

pre-GLP

Type of study:

open epicutaneous test

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

None

Route:

epicutaneous, open

Vehicle:

other: acetone

Concentration / amount:

Preliminary test: 100, 30, 10 and 3 % or lower in acetone

Main test:
- Topical induction exposure: 100, 30, 10 and 3 %
- Topical challenge exposures 1 and 2: Minimal irritating (10 %) and lower concentrations

Route:

epicutaneous, open

Vehicle:

other: acetone

Concentration / amount:

Preliminary test: 100, 30, 10 and 3 % or lower in acetone

Main test:
- Topical induction exposure: 100, 30, 10 and 3 %
- Topical challenge exposures 1 and 2: Minimal irritating (10 %) and lower concentrations

No. of animals per dose:

Eight

Details on study design:

PRELIMINARY TEST:
- Estimation of threshold-toxic concentration: One day before starting the induction procedure, 0.025 mL of each test concentration (100, 30, 10 and 3 % or lower in acetone) was applied directly to the clipped flank skin (2 cm2) of the guinea pigs and the skin reactions were observed after 24 h. The minimal irritant and the maximal non-irritant concentrations were determined by an all-or-none criterion.

MAIN STUDY
A. INDUCTION EXPOSURE: EPICUTANEOUS
- No. of exposures: 21
- Test groups: 0.1 mL of each test concentration was applied directly to the skin of animals and the application sites were left uncovered.
- Site: Clipped flank skin (8 cm2)
- Frequency of applications: Once daily for 3 weeks
- Evaluation of skin reactions: 24 h after application or at the end of each week
- Duration: Days 0-20

B. CHALLENGE EXPOSURE: EPICUTANEOUS
- No. of exposures: Two
- Day of challenge: Days 21 and 35
- Test groups: 0.025 mL of each test concentration was applied directly to the skin and the application sites were left uncovered.
- Site: Contralateral flank skin (2 cm2)
- Evaluation (h after application): 24, 48 and/or 72 h

Challenge controls:

On Days 21 and 35, 0.025 mL of each test concentration was applied directly to the skin of vehicle treated or untreated control animals. The application sites were left uncovered and observed for skin reactions after 24, 48 and/or 72 h.

Positive control substance(s):

no

Positive control results:

Not applicable

Reading:

other: challenge 1 on Day 21 (readings at 24, 48 and/or 72 h)

Hours after challenge:

72

Group:

test chemical

Dose level:

Induction: 3-100 %; challenge: 10 % or lower

No. with + reactions:

0

Total no. in group:

8

Clinical observations:

no data

Remarks on result:

other: see Remark

Remarks:

Reading: other: challenge 1 on Day 21 (readings at 24, 48 and/or 72 h). . Hours after challenge: 72.0. Group: test group. Dose level: Induction: 3-100 %; challenge: 10 % or lower. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: no data.

Reading:

other: challenge 2 on Day 35 (readings at 24, 48 and/or 72 h)

Hours after challenge:

72

Group:

test chemical

Dose level:

Induction: 3-100 %; challenge: 10 % or lower

No. with + reactions:

0

Total no. in group:

8

Clinical observations:

no data

Remarks on result:

other: see Remark

Remarks:

Reading: other: challenge 2 on Day 35 (readings at 24, 48 and/or 72 h). . Hours after challenge: 72.0. Group: test group. Dose level: Induction: 3-100 %; challenge: 10 % or lower. No with. + reactions: 0.0. Total no. in groups: 8.0. Clinical observations: no data.

Preliminary test:

- Lowest irritant concentration: 10 %

- Highest non-irritant concentration: 3 %

Table 7.4.1/1: Main test: skin irritation after repeated applications over 21 successive days

Concentration in %	Skin irritation after days
	7	14	21
100	very slight	very slight	very slight
30	very slight	very slight	very slight
10	very slight	very slight	very slight
3	none	none	none

Table 7.4.1/2: Main test: capacity to induce allergic sensitisation

Concentration in % (after daily applications over 3 weeks)	Sensitisation rate no. of animals positive/total
	Day 21	Day 35
100	0/8	0/8
30	0/8	0/8
10	0/8	0/8
3	0/8	0/8

 

 

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under these test conditions, LRA 303 “CENTIFOLYL” was considered not to be a skin sensitiser to guinea pig.

Executive summary:

In an open epicutaneous test (OET), groups of guinea pigs (8/group) were epicutaneously induced with 0.1 mL of the test item, LRA 303 “CENTIFOLYL”, at concentrations of 100, 30, 10 and 3 % in acetone. Each test concentration was applied directly to the clipped flank skin (8 cm2) of guinea pigs, once daily for 21 successive days (Days 0-20) and the application sites were left uncovered. On Days 21 and 35, 0.025 mL of the test item at the minimal irritating (10 %) and some lower concentrations were applied to the contralateral skin of previously treated and untreated or vehicle treated animals.

No skin reactions were noted at the challenge sites of the test group animals on Days 21 and 35. LRA 303 “CENTIFOLYL” produced a 0% (0/8) sensitisation rate and was considered not to be a skin sensitiser to guinea pig.

Under these test conditions, LRA 303 “CENTIFOLYL” was considered not to be a skin sensitiser to guinea pig.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:
Pivarose was found to be not sensitising in an OET and FCAT test.

Justification for selection of skin sensitisation endpoint:
Reliable in vivo study

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on negative results in two reliable in vivo sensitisation studies, classification under EU DSD or CLP regulations is not required.