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:
experimental study
Adequacy of study:
key study
Study period:
From 23 February 2011 to 05 May 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Test guideline and GLP-compliant study
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
The maximum temperature and the relative humidity during the test were higher than the ones recommended by the test guideline (77% vs. 30-70%). This deviation had no impact on the study result.
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
Buehler test available before that LLNA was requested as first test for sensitization.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Anilab, Paulinia-SP (Brazil)
- Age at study initiation: approximately 5 weeks
- Weight at study initiation: 300.5 to 342 g for males and 317.5 to 356.5g for females
- Housing: in polypropylene cages (40 x 51 x 69 cm) in groups of five animals
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 25 °C
- Humidity (%): average of 77%
- Air changes (per hr): not documented
- Photoperiod (hrs dark / hrs light): 12h/12h

IN-LIFE DATES: From: 23 February 2011 To: 24 March 2011
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
one concentration of 100% (undiluted)
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
one concentration of 100% (undiluted)
No. of animals per dose:
10 animals/sex for the treated group and 5 animals/sex for the control group
Details on study design:
RANGE FINDING TESTS: 0.5 mL of the test substnce was dermally applied undiluted (100%) on the skin of one male and one female guinea pig. Since no skin reaction was observed in the animals after 72, the concentration of 100% was chosen for the induction and challenge exposures in the main test.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3 applications (Days 0, 7 and 15)
- Exposure period: 3 weeks
- Test groups: 0.5 mL of the test substance at 100% (undiluted)
- Control group: 0.5 mL of deionized water
- Site: left flank using an occlusive patch.
- Frequency of applications: one per week for 3 weeks
- Duration: 6 hours/application
- Concentrations: only one concentration of 100%

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: Day 27
- Exposure period: 6 hours
- Test groups: 0.5 mL of the test substance at 100% (undiluted)
- Control group: 0.5 mL of the test substance at 100% (undiluted)
- Site: untreated right flank using an occlusive patch
- Concentrations: only one concentration of 100%
- Evaluation (hr after challenge): 24 and 48 hours after patch removal

OTHER:
- Following the induction period, the animals received no treatment for 11 days (from day 16 to day 26).
- Skin reactions were evaluated for development of edema and erythema according to the criteria of Buehler Senstization scoring scale (Ritz, H and Biehler, E., 1980).
Positive control substance(s):
yes
Remarks:
alpha-hexylcinnamaldehyde
Positive control results:
The last reliability check (performed in 2010) showed that the positive control alpha-hexylcinnamaldehyde induces positive skin sensitising reactions in 55% (11/20) guinea pigs and it was concluded that the test conditions and animal strain chosen are able to reveal the known skin senstizing effect of the test substance in the guinea pig Buehler test.
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
induction and challenge: 100%
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction and challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
induction and challenge: 100%
No. with + reactions:
0
Total no. in group:
19
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction and challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 19.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0% ; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0% ; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0% ; challenge: 100%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: induction: 0% ; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.

Clinical signs and mortality:

No systemic toxicity was observed during the period of test among the control animals. On Day 11, one female from the treated group was found dead; this mortality represents less than 10% of total animals and was considered without impact on the study outcome. All surviving animals had normal body weight gain during the experimental period.

Neither erythema nor edema was observed in the left flank during the period of the test.

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The registered substance 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is not sensitizing to skin according to the criteria of this test.
Executive summary:

A skin sensitizing study was performed with 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol in Dunkin-Hartley guinea pigs according to the Buehler test method (OECD 406 Guideline) and in compliance with the GLP.

A preliminary test was carried out initially with one male and one female. Test substance (0.5 mL) was applied dermally undiluted (100%). Since no irritation was observed in both animals, the concentration of 100% was applied in the main test.

In the main test, thirty adults and healthy guinea pigs were divided in 2 groups: treatment group with 10 animals/sex and control group with 5 animals/sex. In the period of induction, three applications were carried out on the left flank of each animal using an occlusive patch fully loaded with 0.5 mL of the test substance undiluted (treatment group) or 0.5 mL of deionized water (control group), held in contact for 6 hours on days 0, 7 and 15. On day 11, one female from the treated group was found dead; this mortality represents less than 10% of total animals and was considered without impact on the study outcome. At day 27, challenge exposure was started: an occlusive patch fully loaded with 0.5 mL of the test substance undiluted was applied to the right untreated flank of both treated and control animals. The patches were held in contact for 6 hours. Approximately 24 and 48 hours after removing the patches, skin reactions (development of edema and erythema) were evaluated. Neither erythema nor edema was observed in any animals. No clinical signs of toxicity and no effect on body weight gain were observed during the experimental period.

In conclusion, 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol does not require classification as a skin sensitizer according to the Regulation (EC) 1272/2008 (CLP) and GHS UN criteria.

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

On study of reliability 1 according to Klimisch cotation criteria is available for the evaluation of the skin sensitizing effect (P.M. Fagundes, 2011) and was selected as a key study. Thestudy was performed in Dunkin-Hartley guinea pigs according to the Buehler test method (OECD 406 Guideline) and in compliance with the GLP.

A preliminary test was carried out initially with one male and one female. Test substance (0.5 mL) was applied dermally undiluted (100%). Since no irritation was observed in both animals, the concentration of 100% was applied in the main test.

In the main test, thirty adults and healthy guinea pigs were divided in 2 groups: treatment group with 10 animals/sex and control group with 5 animals/sex. In the period of induction, three applications were carried out on the left flank of each animal using an occlusive patch fully loaded with 0.5 mL of the test substance undiluted (treatment group) or 0.5 mL of deionized water (control group), held in contact for 6 hours on days 0, 7 and 15. On day 11, one female from the treated group was found dead; this mortality represents less than 10% of total animals and was considered without impact on the study outcome. At day 27, challenge exposure was started: an occlusive patch fully loaded with 0.5 mL of the test substance undiluted was applied to the right untreated flank of both treated and control animals. The patches were held in contact for 6 hours. Approximately 24 and 48 hours after removing the patches, skin reactions (development of edema and erythema) were evaluated. Neither erythema nor edema was observed in any animals. No clinical signs of toxicity and no effect on body weight gain were observed during the experimental period.

 According to Regulation (EC) No 1272/2008 and UN Globally Harmonised System of Classification and Labelling of Chemicals, 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol does not require classification as a skin sensitizer.


Migrated from Short description of key information:
The name of the tested substance for the skin and eye irritation studies was PEX-2, the previous public name of 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol. The specifications of PEX-2 are in line with the dossier and representative of the industrial product.
One skin sensitization study (P.M. Fagundes, 2011; OECD 406 (Buehler method); Rel. 1) is available and showed that the registered susbstance is not sensitizing to skin.

Justification for selection of skin sensitisation endpoint:
only one study available (GLP and OECD guideline 406 compliant)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

The substance does not fulfill the criteria for classification as "sensitizing to skin" according to Regulation (EC) No 1272/2008 because no skin reactions were observed in any animals 24 and 48 hours after the challenge exposure in a Buehler test.