α-tocopheryl hydrogen succinate

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

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:

guideline 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

GLP compliance:

yes (incl. QA statement)

Type of study:

other: Photoallergenicity test

Justification for non-LLNA method:

Presented study was conducted before OECD Guideline 429 was adopted.

Test material

Test material information

Constituent 1

Reference substance name:

[(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate

Cas Number:

7695-91-2

Molecular formula:

C31H52O3

IUPAC Name:

[(2R)-2,5,7,8-tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydrochromen-6-yl] acetate

Specific details on test material used for the study:

- 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:

Himalayan

Remarks:

spotted (GOHI SPF-quality)

Sex:

female

Study design: in vivo (non-LLNA)

Induction

Route:

intradermal and epicutaneous

Vehicle:

other: ethanol

Concentration / amount:

Induction: 100% (undiluted)

Day(s)/duration:

2 weeks

Adequacy of induction:

not specified

Challenge

No.:

#20

Route:

epicutaneous, open

Vehicle:

other: ethanol

Concentration / amount:

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

Day(s)/duration:

72 h

Adequacy of challenge:

not specified

No. of animals per dose:

Control group: 10, test group: 20

Results and discussion

In vivo (non-LLNA)

Results

Results 1

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

100% (undiluted), 75%, 50%, and 25%

No. with + reactions:

2

Total no. in group:

20

Results 2

Key result

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

0%

No. with + reactions:

0

Total no. in group:

0

Results 3

Key result

Reading:

2nd reading

Group:

positive control

Remarks on result:

other: not reported

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:

GHS criteria not met

Conclusions:

Under the study conditions, the test substance does not exhibit photoallergenic potential in the guinea pig.

Executive summary:

A study was conducted to determine the photoallergenic potential of the test substance according to the CTFA Safety Testing Guidelines. The photoallergenicity tests were carried out in 30 female (20 test and 10 control) Himalayan spotted guinea pigs. For the induction of sensitization the undiluted test substance 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 hours 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 dependent on the test substance concentration and most likely resulted from cutaneous hyperirritability (angry back) of the animals. No reactions were observed in the control group. Under the study conditions, the test substance does not exhibit photoallergenic potential in the guinea pig (Csato, 1996).