Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1 April 1996 - 30 April 1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: RA study
Justification for type of information:
Refer to the section 13 for details on the read across justification.
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
other: CTFA Guideline for Evaluating Photodermatitis (Photoallergenicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
other: Photoallergenicity test
Justification for non-LLNA method:
Presented study was conducted before OECD Guideline 429 was adopted.
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
Species:
guinea pig
Strain:
Himalayan
Remarks:
spotted (GOHI SPF-quality)
Sex:
female
Route:
intradermal and epicutaneous
Vehicle:
other: ethanol
Concentration / amount:
Induction: 100% (undiluted)
Day(s)/duration:
2 weeks
Adequacy of induction:
not specified
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
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test group
Dose level:
100% (undiluted), 75%, 50%, and 25%
No. with + reactions:
2
Total no. in group:
20
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
0%
No. with + reactions:
0
Total no. in group:
0
Key result
Reading:
2nd reading
Group:
positive control
Remarks on result:
other: not reported

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.

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results of the read across study, 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 read across 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 substance at 100% (undiluted), 75%, 50% and 25% (dilutions in ethanol). Treated sites were then either exposed to 10 J/cm2 UVA irradiation (left flank) or remained unirradiated (right flank). Cutaneous reactions, i.e. erythema and oedema formation were evaluated at 24, 48 and 72 h after the challenge exposure. 2 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 of the animals. No reactions were observed in the control group. Based on the results of the read across study, the test substance was not found to exhibit photoallergenic potential in the guinea pig (Csato, 1996).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A study was conducted to determine the photoallergenic potential of the read across 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 substance at 100% (undiluted), 75%, 50% and 25% (dilutions in ethanol). Treated sites were then either exposed to 10 J/cm2 UVA irradiation (left flank) or remained unirradiated (right flank). Cutaneous reactions, i.e. erythema and oedema formation were evaluated at 24, 48 and 72 h after the challenge exposure. 2 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 of the animals. No reactions were observed in the control group. Based on the results of the read across study, the test substance was not found to exhibit photoallergenic potential in the guinea pig (Csato, 1996).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The available in vivo study with the read across substance, dl-alpha-tocopheryl acetate, indicates that the test substance is not a skin sensitiser. The substance is therefore not classified according to EC (67/548/EEC) and CLP (EC 1272/2008) criteria.