reaction mass of isomers of: C7-9-alkyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Study period:

1/14/2000 to 11/29/2000

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP; Study conducted in accordance with recognized guideline. There are minor deviations from the guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Version / remarks:

OECD Guidelines for the Testing of Chemicals, Section 4, Health Effects, Subsection 406, July 17, 1992.

Deviations:

yes

Principles of method if other than guideline:

Analytical purity and acclimation period are not reported

GLP compliance:

yes (incl. QA statement)

Type of study:

Buehler test

Test material

Test material information

Constituent 1

Details on test material:

-Name of test material (as cited in study report): OS#144267
- Molecular formula (if other than submission substance): C21H34O3
- Molecular weight (if other than submission substance): 334.491
- Smiles notation (if other than submission substance): Oc1c(C(C)(C)C)cc(cc1C(C)(C)C)CCC(=O)OCCCC
- InChl (if other than submission substance): 1S/C21H34O3/c1-8-9-12-24-18(22)11-10-15-13-16(20(2,3)4)19(23)17(14-15)21(5,6)7/h13-14,23H,8-12H2,1-7H3
- Structural formula attached as image file (if other than submission substance): see Fig.1
- Substance type: alkylated phenol
- Physical state: Yellow crystalline solid
- Analytical purity: information not available
- Stability under test conditions: The Sponsor was responsible for any necessary evaluations related to identity, strength, purity, composition, stability and method of synthesis of the test material according to 40 CFR 792.105 and [C(97)186/Final]
- Storage condition of test material: at room temperature
- Other: receipt date: January 13, 2000

In vivo test system

Test animals

Species:

guinea pig

Strain:

Hartley

Sex:

male/female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Hilltop Lab Animals, Inc., Scottdale, PA, USA.
- Age at study initiation: Young adult; no specific age noted.
- Weight at study initiation: 300-500 g
- Housing: The animals were housed individually in suspended stainless steel cages based on standards recommended by the Guide for Care and Use of Laboratory Animals, DHHS Publication No. (NIH) 96-103, 1996.
- Diet (e.g. ad libitum): PMI Certified Guinea Pig Chow #5026 (Purina Mills, Inc.) was provided ad libitum.
- Water (e.g. ad libitum): Municipal tap water was provided ad libitum.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 65-71 °F (18-22° C)
- Humidity (%): 24-59. The relative humidity of the animal room (24-59%) exceeded the preferred range (30-70%) during this study. This occurrence was considered to have had no adverse effect on the outcome of this study.
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle.

IN-LIFE DATES: From: 27 January 2000 To: 2 March 2000

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Induction 2

Concentration / amount:

- Test material: 100% w/v for induction and challenge control;
- Positive control substance: 0.1 % w/v DNCB in acetone/ethanol for induction and 0.1 % and 0.05% w/v DNCB in acetone/ethanol for challenge.

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

other: mineral oil

Challenge 2

Concentration / amount:

- Test material: 100% w/v for induction and challenge control;
- Positive control substance: 0.1 % w/v DNCB in acetone/ethanol for induction and 0.1 % and 0.05% w/v DNCB in acetone/ethanol for challenge.

No. of animals per dose:

10 males/10 females (test material);
5 males/5 females (challenge control, positive control, positive challenge control)

Details on study design:

RANGE FINDING TESTS: 0.3 mL of test material at concentrations of 25, 50, 75, and 100% w/v were applied to four guinea pigs, two per sex. The test sites were graded for irritation at 24 and 48 hours following chamber application. Body weights were obtained on the day prior to dosing. The results of the range-finding study indicated that a test article concentration of 100% was considered appropriate for induction.
MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 (once per week)
- Exposure period: 3 weeks
- Test groups: 1 group of 10 animals per sex.
- Control group: test material challenge control, positive control, positive challenge control (5 animals per sex).
- Site: trunk area
- Frequency of applications: Once per week for three weeks for the induction phase . After a two week rest period, the test and control animals were challenged by applying the test substance to the test and challenge control groups. DNCB was applied to the DNCB test and control groups. The sites were wiped with gauze moistened with deionized water after 6 hours; the test sites were graded at 24 and 48 hours post chamber application.
- Duration: total of 32 days including induction, rest, and challenge periods.
- Concentrations: Test substance: 100%; 0.1 % w/v DNCB in acetone/ethanol.

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Exposure period: 6 h
- Test groups: 1 group of 5 animals per sex.
- Control group: DNCB.
- Site: trunk area.
- Concentrations: Test substance: 100%; 0.1 % and 0.05% w/v DNCB in acetone/ethanol.
- Evaluation (hr after challenge): 24 hr and 48 hr following chamber application

Challenge controls:

Yes. Test substance and DNCB challenge controls were included

Positive control substance(s):

yes

Remarks:

1-chloro-2,4-dinitrobenzene (DNCB)

Study design: in vivo (LLNA)

Statistics:

ANALYSIS OF DATA
The sensitization potential of the test article was based on the dermal responses observed on the test and control animals at challenge. Generally, dermal scores of 21 in the test animals with scores of 0 to f noted in the controls are considered indicative of sensitization. Dermal scores of I in both the test and control animals are generally considered equivocal unless a higher dermal response (2 grade 2) is noted in the test animals. Group mean dermal scores were calculated for challenge.

Results and discussion

Positive control results:

Following challenge with DNCB, all DNCB test animals were noted to have a substantially stronger dermal response than was observed in the corresponding DNCB control animals. Group mean dermal scores were also noted to be higher in the DNCB test animals as compared to those of the DNCB control animals.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100% w/v

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

dermal scores were the same in the test animals and in the challenge control animals

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100% w/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: dermal scores were the same in the test animals and in the challenge control animals.

Results 2

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100% w/v

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

dermal scores were the same in the test animals and in the challenge control animals

Remarks on result:

other: see Remark

Remarks:

Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100% w/v. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: dermal scores were the same in the test animals and in the challenge control animals.

Any other information on results incl. tables

Range-finding study

The results of the range-finding study indicated that a test article concentration of 100% was considered appropriate for induction.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is not considered to be a contact sensitizer in guinea pigs. The results of the DNCB positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitizers.

Executive summary:

GLP sensitisation study (Modified Buehler Method Test) was performed according to the EPA sensitisation guideline OPPTS 870.2600 without deviations and therefore considered to be of the highest quality (reliability: Klimish 1).

According to the study protocol, 10 albino Guinea Pigs per sex were treated with 100% w/v test substance. Scores of zero in all test animals were obtained in the challenge phase at all time points examined. 1-chloro-2,4-dinitrobenzene (DNCB) served as positive control substance. Following challenge with DNCB, all DNCB test animals were noted to have a substantially stronger dermal response than was observed in the corresponding DNCB control animals. Group mean dermal scores were also noted to be higher in the DNCB test animals as compared to those of the DNCB control animals. Based on the results of this study, the test material is not considered to be a contact sensitizer in guinea pigs. The results of the DNCB positive control study demonstrated that a valid test was performed and indicated that the test design would detect potential contact sensitizers.