3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1 April 1996 - 30 April 1996

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study was conducted under GLP and according to the Personal Care Products Council (formerly CTFA) Guideline for Evaluating Photodermatitis.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: CTFA Guideline for Evaluating Photodermatitis (Photoallergenicity)

Deviations:

no

Principles of method if other than guideline:

Not relevant

GLP compliance:

yes (incl. QA statement)

Type of study:

other: Photoallergenicity test

Test material

Test material information

Constituent 1

Reference substance name:

3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate

EC Number:

231-710-0

EC Name:

3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-2H-benzopyran-6-yl acetate

Cas Number:

7695-91-2

Molecular formula:

C31H52O3

IUPAC Name:

2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)-3,4-dihydro-2H-1-benzopyran-6-yl acetate

Details on test material:

- Name of test material (as cited in study report): dl-Alpha-Tocopheryl Acetate
- Physical state: Liquid
- Stability under test conditions: Unknown in ethanol, but stable under storage conditions
- Storage condition of test material: In the original container, at room temperature under nitrogen or argon atmosphere, protected from light

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Himalayan spotted (GOHI SPF-quality)

Sex:

female

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

other: ethanol

Induction 2

Concentration / amount:

Induction: 100% (undiluted)
Challenge: 100% (undiluted), 75%, 50%, and 25%

Challenge

Challenge 1

Route:

epicutaneous, open

Vehicle:

other: ethanol

Challenge 2

Concentration / amount:

Induction: 100% (undiluted)
Challenge: 100% (undiluted), 75%, 50%, and 25%

No. of animals per dose:

Control group: 10, test group: 20

Study design: in vivo (LLNA)

Vehicle:

other: Not relevant

Concentration:

Not relevant

No. of animals per dose:

Not relevant

Results and discussion

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: Not relevant

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: Not relevant

Any other information on results incl. tables

Induction:

After intradermal induction erythema, oedema, necrotizing dermatitis and exfoliation of encrustation were observed.

After epidermal induction no positive skin reactions were observed.

Challenge:

After challenge two out of 20 animals were observed with a slight erythematous skin reaction after challenge. No consistent or significant differences were detected between the radiated and irradiated test sites of animals. See table below for the results.

No spontaneous deaths occurred, no symptoms of systemic toxicity were observed and the body weight was within the normal range of variability.

Erythema reactions after challenge
	Concentration (%)	Left flank (UV-A irradiated)			Right flank (non-irradiated)
		% with positive reaction			% with positive reaction
		24 hrs	48 hrs	72 hrs	24 hrs	48 hrs	72 hrs
Test group (dl-alpha-tocopheryl acetate, n=20)	100	0	0	0	5	5	5
	75	5	5	10	10	10	10
	50	5	5	10	5	5	5
	25	0	0	0	0	0	0
Control group (n=10)	100	0	0	0	0	0	0
	75	0	0	0	0	0	0
	50	0	0	0	0	0	0
	25	0	0	0	0	0	0

In only 10% (2 out of 20) test animal slight erythematous skin reactions were observed after challenge. Those reactions were not clearly dependent on the test article concentration and most likely resulted from cutaneous hyperirritability (angry back) of the animals.

Applicant's summary and conclusion

Interpretation of results:

other: Not photoallergenic

Conclusions:

Since no consistent or significant differences were seen between the irradiated and non-irradiated test sites of the animals, it can be concluded that dl-Alpha-Tocopheryl Acetate does not exhibit photoallergenic potential in the guinea pig under the study conditions.

Executive summary:

In order to assess the photoallergenic potential of dl-Alpha-Tocopheryl Acetate, a photoallergenicity test according to the CTFA Safety Testing Guidelines was carried out in 30 female (20 test and 10 control) Himalayan spotted guinea pigs.

For the induction of sensitization the undiluted dl-Alpha-Tocopheryl Acetate was applied epicutaneously to a skin area of 8 cm2 (marked previously with 4 intradermal injections of Freund’s Complete Adjuvant). The test sites were then exposed to 1.8 J/cm2 UVB and 10 J/cm2 UVA irradiation. This procedure was repeated 4 times within 2 weeks of the induction phase. Control animals were treated with FCA only. Three weeks after beginning of the induction a challenge was carried out by treating the experimental animals (test and control) epicutaneously on both flanks with the test article at the concentrations of 100% (undiluted), 75%, 50% and 25% (dilutions in ethanol). Treated sites were then either exposed to 10 J/cm UVA irradiation (left flank) or remained unirradiated (right flank). Cutaneous reactions, i.e. erythema and oedema formation were evaluated at 24, 48 and 72 hrs after the challenge exposure.

Two out of 20 test animals were observed with a slight erythematous skin reaction after challenge. No consistent or significant differences were detected between the irradiated and non-irradiated test sites of the animals The reactions were not clearly denendent on the test article concentration and most likely resulted from cutaneous hyperirritability (angry back) of the animals. No reactions were observed in the control group.

Considering the above experimental data it can be concluded that dl-Alpha-Tocopheryl Acetate does not exhibit photoallergenic potential in the guinea pig under the study conditions. It can be assumed accordingly that the risk that dl-Alpha-Tocopheryl Acetate could elicit a cutaneous photoallergenic reaction in humans is low if any.