Registration Dossier

Administrative data

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 Acute skin irritation study and one acute eye irritation study (L.F. Negro Silva, 2011; OECD 404 and 405 respectivel; Rel. 1) are available and showed that the registered susbstance is severely irritating to eyes. It is not irritating to skin.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 15 February 2011 to 16 August 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Test guideline and GLP-compliant study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: PROSPERO, CESARIO Lange-SP
- Age at study initiation: around 3 months
- Weight at study initiation: 1.9 to 2.9 kg
- Fasting period before study: approximately 12 hours prior to the test substance administration
- Housing: individually in alvanized metal cages ( 50 x 50 x 50 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 60 to 66%
- Air changes (per hr): not documented
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 15 February 2011 To: 18 February 2011
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: none (substance applied undiluted)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL per animal on a 6 cm2 skin area.
- Concentration (if solution): 100%

Duration of treatment / exposure:
4 hours
Observation period:
1, 24, 48 and 72 hours after patch removal
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: approximately 6 cm2
- Type of wrap if used: Treated areas were covered with a gauze patch held in place with a non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test substance was removed using deionized water
- Time after start of exposure: 4 hours

SCORING SYSTEM:according to Draize scale
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24-48-72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable since no erythema was observed at 24, 48 and 72h
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 24-48-72h
Score:
0
Max. score:
0
Reversibility:
other: not applicable since no edema was observed at 24, 48 and 72h
Irritant / corrosive response data:
Nor edema nor erythema were seen during the observation period in the treated areas of all rabbits at 1, 24, 48 and 72 hours.

No mortality nor treatment related clinical signs were observed during the observation period.

No effect on body weight gain was reported.

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

An acute skin irritation study was performed with 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol in New Zealand White rabbits according to the OECD 404 Guideline and in compliance with the GLP.

Three male rabbits were employed. The test substance (0.5 mL) was applied undiluted to an area of 6 cm2 of the left flank previously shaved and covered with a gauze patch. Adjacent non-treated areas of the right flank were used as control. After 4 hours, residual test substance was removed using deionized water. The animals were observed at 1, 24, 48 and 72 hours after patch removal to assess the signs of erythema and edema according to the Draize method. Additionnal general examinations were performed daily.

No systemic toxicity or abnormality in body weight gain occured during the observation period. No edema or erythema was observed at 1, 24, 48 and 72 hours in any animals. Test was concluded at 72 hours since no reaction was observed.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 22 February to 16 August 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Test guideline and GLP-compliant study
Reference:
Composition 0
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test material information:
Composition 1
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Coelhario Prospero, Cesario Lange - SP and Coelhario Natanael Alves Ferreira, Sao Roqsue - SP
- Age at study initiation: 2 to 3 months
- Weight at study initiation: 1.8 to 2.7 kg
- Fasting period before study: approximately 12 hours prior to the test substance administration
- Housing: individually in alvanized metal cages ( 50 x 50 x 50 cm)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 24°C
- Humidity (%): 58 to 66%
- Air changes (per hr): not documented
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 22 February 2011 To: 21 April 2011
Vehicle:
other: non since the substance was tested undiluted
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):0.1mL
- Concentration (if solution): 100%
Duration of treatment / exposure:
single instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3 males
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes, with deionised water
- Time after start of exposure: 24 hours

SCORING SYSTEM: The eyes were examined at various times after application (1 hours, 24h, 48h, 48h and 72h) for signs of irritation in the iris, cornea (opacity and affected area) and conjonctivae (chemosis and conjunctival redness) according to Draize method (OCDE, 2002)

TOOL USED TO ASSESS SCORE: not documented
Irritant / corrosive response data:
see summary Table 7.3.2.1

Table 7.3.2.1: Individual grading of eye reactions (scores)

Rabbit N°

Time

Opacity

Affected area

Iritis

Conjunctival redness

Chemosis

1

1h

1

-

1

2

3

24h

1

2

1

2

3

48h

0

0

1

1

1

72h

0

0

0

0

0

Mean*

0.3

-

0.7

1.0

1.3

2

1h

1

-

1

1

3

24h

2

4

1

2

1

48h**

1

4

1

3

3

3

1h

1

-

1

2

2

24h

2

4

1

2

1

48h**

2

4

1

3

3

* mean values calculated as the mean scores of readings at 24, 48 and 72 hours.

** presence of ulcer

Interpretation of results:
Category 1 (irreversible effects on the eye) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The registered substance 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is severely irritating to eyes according to the criteria of this test.
Executive summary:

An acute eye irritation study was performed with 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol in New Zealand White rabbits according to the OECD 405 Guideline and in compliance with the GLP.

Three male rabbits were employed. The test substance (0.1 mL) was applied undiluted into the left eye of each rabbit. The contralateral eye was used as control. The eyes of the rabbits were then evaluated at various times after application (1, 24, 48 and 72 hours for the first animal tested and 1, 24 and 48 hours for the second and third animals tested) for signs of ocular reactions in the iris, cornea and conjunctivae. Irritation was scored according to the Draize method.

No systemic toxicity or abnormality in body weight gain was detected during the observation period.

In the first animal tested, conjunctivae redness, chemosis and iritis were observed during evaluation of 1, 24 and 48 hours. Opacity was observed at 1 hour of evaluation until 24 hours. On day 3, all ocular effects were reverted. In the second and third animals tested, corneal opacity, iritis, chemosis and conjunctival redness were observed during evaluations of 1, 24 and 48 hours. At 48 hours, corneal ulceration, considered irreversible lesion, was observed and the test was terminated.

In conclusion, 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol requires classification as eye corrosive (Category 1; irreversible effects on the eye) according to the Regulation (EC) 1272/2008 (CLP) and GHS UN criteria.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation:

On study of reliability 1 according to Klimisch cotation criteria, is availablefor the evaluation of the skin effect (L.F. Negro Silva, 2011)and was selected as a key study. In this study (OECD 404), 3 New Zealand White rabbits were treated by a topical semi-occlusive application of 0.5 mL of undiluted 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol for 4 hours and were observed 1, 24, 48 and 72 hours after exposure.

There was no mortality or systemic clinical changes related to Augeo Clean Plus administration. There was no effect of treatment on body weight. At observation one, 24, 48 and 72 hours after patch removal, no edema neither erythema were seen in any animals. As no local reactions were observed up to 72 hours after patch removal, the study was terminated after the 72 hours observation. The animals’ individual mean scores (considering readings at 24, 48 and 72 hours after patch removal) for erythema and oedema were 0, 0, and 0 respectively.

Based upon the referred classification criteria (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 is considered to be "not irritating" to rabbit skin.

 Eye irritation:

On study of reliability 1 according to Klimisch cotation criteria, is available for the evaluation of the eye effect (L.F. Negro Silva, 2011) and was selected as a key study. In this study (OECD 405), 3 New Zealand White rabbits were treated by an ocular instillation of 0.1 mL of undiluted 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol and were observed at various times after application (1, 24, 48 and 72 hours for the first animal tested and 1, 24 and 48 hours for the second and third animals tested).

No systemic toxicity or abnormality in body weight gain was detected during the observation period . In the first animal tested, conjunctivae redness, chemosis and iritis were observed during evaluation of 1, 24 and 48 hours. Opacity was observed at 1 hour of evaluation until 24 hours. On day 3, all ocular effects were reverted. In the second and third animals tested, corneal opacity, iritis, chemosis and conjunctival redness were observed during evaluations of 1, 24 and 48 hours. At 48 hours, corneal ulceration, considered irreversible lesion, was observed and the test was terminated.

 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 requires classification as an eye corrosive (Category 1; irreversible effects on the eye).


Justification for selection of skin irritation / corrosion endpoint:
only one study available (GLP and OECD guideline 404 compliant)

Justification for selection of eye irritation endpoint:
only one study available (GLP and OECD guideline 405 compliant)

Effects on eye irritation: highly irritating

Justification for classification or non-classification

The substance is classified as an eye corrosive (Xi; R41 or Eye irrit. 1, H318 according to Directive 67/548/EEC or Regulation (EC) 1272/2008, respectively) because significant corneal (ulcerations) and conjunctivae effects were observed up to 48 hours after application.

The substance does not fulfill the criteria for classification as "irritating to skin" according to Regulation (EC) No 1272/2008 because no local effects were observed 24, 48 and 72 hours after application.