Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Skin sensititsation (OECD 406, Guinea Pig Maximisation Test): not sensitising

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
07 Mar - 07 Apr 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
Basic data given (comparable to guideline study). Lack of individual test results and test material details. No data on reliablility check (positive control)
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
yes
Remarks:
lack of individual test results and test material details. No data on reliability check (positive control)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.
Species:
guinea pig
Strain:
other: Pirbright white
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Fa. Winkelmann, Borchen, Germany
- Weight at study initiation: 352.6 g (control group, range finding study) and 349.4 g (treatment group, range finding study); 298.5 g (control group, main study) and 298.4 g (treatment group, main study)
- Housing: animals were housed in groups of 2-3 in Makrolon IV cages
- Diet: Altromin-Haltungsdiät 3032 DK (Fa. Altromin GmbH, Lage, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 50-60
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: Paraffin perliquid DAB 8
Concentration / amount:
Intradermal induction: 0.1%
Epicutaneous induction: 15%
Day(s)/duration:
intradermal induction: single treatment; epicutaneous induction: 48 h
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: Paraffin perliquid DAB 8
Concentration / amount:
2.5% on one flank, 5% on the other flank
Day(s)/duration:
24 h
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
2 x 3 (range finding study)
20 (main study)
Details on study design:
RANGE FINDING TESTS:
Test group A:
To evaluate the concentration for intracutaneous induction 3 guinea pigs were tested with 0.1, 0.5, 1.0 and 2.0% (intracutaneous) of the test substance. The 0.1% concentration of the intracutaneous application caused a sufficient irritation on the skin. Therefore, a 0.1% concentration was chosen for intracutaneous induction exposure.
Test group B:
To evaluate the epicutaneous induction and the challenge concentration, 3 guinea pigs were tested with 5, 10 and 15% (epicutaneous) with the test substance. Due to the only slight skin reactions at 15%, this concentration was chosen for epicutaneous induction and 2.5 and 5% as challenge concentration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: the test substance in Paraffin perliquid DAB 8
Injection 3: the test substance in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in Paraffin perliquid DAB 8

- Control group:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: Paraffin perliquid DAB 8
Injection 3: Paraffin perliquid DAB 8 in a 1:1 mixture (v/v) FCA/water
Epicutaneous: test substance in Paraffin perliquid DAB 8

- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-8
- Concentrations: intradermal 0.1%, epicutaneous 15%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 20
- Exposure period: 24 h
- Test groups: test substance
- Control group: test substance
- Site: parallel application onto the flank
- Concentrations: 2.5 and 5%
- Evaluation (hr after challenge): 24 and 48 h
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0.1%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 0.1%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.1%
No. with + reactions:
1
Total no. in group:
20
Clinical observations:
slight redness of the skin
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0.1%. No with. + reactions: 1.0. Total no. in groups: 20.0. Clinical observations: slight redness of the skin.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 0.1%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Group:
positive control
Remarks on result:
not measured/tested

No mortality was observed in any control or treatment animal.

The individual body weights of the control and test animals showed the expected values.

After intracutaneous induction all animals showed the characteristic reactions after application of FCA (Freund´s complete adjuvant). The test substance without FCA caused moderate skin reactions which were of a lower grade than the reactions caused by FCA alone or by the solution of FCA with the test substance.

After patch removal after the second induction (epicutaneous induction) bloody skin alterations were observed. Later on, this skin reactions changed to necrotic and escharic skin reactions.

24 and 48 h after patch removal (challenge induction) no skin reaction was observed in the treatment animals. In 1 control animal (animal No. 16; 48 h reading) a slight reaction was apparent. According to the author, the results were therefore not presented in table form.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
20 Jun - 21 Aug 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No data on reliability check included.
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data on reliability check included.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.
Species:
guinea pig
Strain:
other: Dunkin Hartley, Pirbright White Bor: DHPW [SPF]
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: 390 - 532 g (males)
- Housing: animals were housed in groups of at the most 5 animals in Makrolon IV cages.
- Diet: Ssniff G4 - Alleindiät für Meerschweinchen (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: tap water (Gelsenwasser, Haltern, Germany), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Intradermal induction: 10%
Epicutaneous induction: 100%
Day(s)/duration:
intradermal induction: single treatment; epicutaneous induction: 48 h
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
100%
Day(s)/duration:
24 h
Adequacy of challenge:
other: concentration selected based on a preliminary range-finding study in which no irritation was observed
No. of animals per dose:
Range finding study:
2 (intradermal application)
4 (epicutaneous application)

Main study:
10 (controls), 20 (in test group)
Details on study design:
RANGE FINDING TESTS:
To assess the intracutaneous tolerability of the test substance 2 animals were treated on the left shoulder region. The intracutaneous treatment was applied to groups of 2 animals in concentrations of 0.25, 0.5, 1.0, 2.5, 5.0 and 10.0% in the vehicle corn oil, and evaluated 24 h post appication. Occlusive dermal application of the test substance was conducted in 4 animals for 24 h in concentrations of 2.5, 25, 50 and 100% of the test substance. Dermal reactions were evaluated 48 and 72 h after application. Results of the prelimimary test are presented in Table 1 under "Any other information on results incl. tables".
Based on the results of the range finding test, concentrations of 10% and 100% were selected for intradermal and epicutanous trestment, respectively.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/NaCl solution
Injection 2: test substance in corn oil
Injection 3: test substance in a 1:1 mixture (v/v) FCA/NaCl solution
Epicutaneous: test substance
- Control group I+II:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/NaCl solution
Injection 2: corn oil
- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-7
- Concentrations: intradermal 10%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 h
- Test groups: test substance
- Control group I: test substance
- Control group II: vehicle control is employed only in the induction treatment; no challenge with vehicle
- Site: left flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72 h
SCORING SYSTEM:
Skin reactions (erythema, eschar formation and edema) were evaluated according to the scheme presented in Table 1 under "Any other information on materials and methods incl. tables".

OTHER:
The highest concentration of test substance administered dermally in the preliminary test caused no irritation of the skin. In order to cause slight to moderate inflammation of the skin for the dermal induction, one day before the dermal administration (Day 6) all the test and control animals were sheared on the shoulder and treated with sodium dodecyl sulphate (10%).
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
not specified
Remarks:
According to the author, the reliability of the test system is checked at regular intervals (no details provided).
Key result
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
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: negative control I. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction: 10%; challenge: 100%
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 10%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 19.0.
Key result
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
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: negative control I. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 10%; challenge: 100%
No. with + reactions:
0
Total no. in group:
19
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction: 10%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 19.0.
Key result
Group:
positive control
Remarks on result:
other: According to the author, the reliability of the test system is checked at regular intervals (no details provided).

Table 1. Results of the intradermal application (preliminary test).

Concentration

(w/w)

animal 1

   E   O

animal 2

 E O 

0.25

2

2

2

2

0.5

2

2

2

2

1.00

2

2

2

2

2.5

2

2

2

2

5.0

1

2

2

2

10.00

1

2

1

2

corn oil

2

2

1

1

PRELIMINARY TEST

Dermal application

After 24, 48 and 72 h, no skin reaction was observed in the test animals in the concentration 2.5, 25 and 50% of the test substance. After 24 h very slight erythem and edema were observed in 2/4 animals being fully reversible after 48 h.

MAIN TEST

- Bodyweight changes and systemic effects:

No toxic effects were observed in the treated animals during the observation period.

One animal died within 24 h after the dermal induction. Possibly, the animal was too strong bandaged resulting in dyspnoea and death. Necropsy revealed a clear yellow liquid in the thorax and no further abnormal organ findings.

- Results of the intradermal induction:

One h after injection of FCA all test and control animals showed severe erythema and oedema. 11/20 test animals and 6/20 control animals showed injuries in the depth. 24 h later all animals showed severe erythema and oedema.

24 h after test substance injection all test animals showed slight erythema and oedema comparable to the control animals. Injection of test substance and FCA (1:1) induced moderate to strong erythema and moderate oedema. After 24 h strong erythema with deep injuries in 8/20 test animals and strong oedema were observed. Control animals injected with 50% FCA and corn oil showed 1 h after application well defined erythema and slight oedema. 24 h post application severe erythema with deep injuries (3/20) and strong oedema were observed.

 

- Results of the dermal induction:

Due to the use of SDS the shoulder region was reddened and swollen at Day 7. All test and control animals treated with FCA showed 49 h post application severe erythema with deep injuries and eschar formation and severe oedema. After 72 h the application sites of all animals were swollen and eschar formation was apparent. The animals treated with test substance in the vehicle showed 49 and 72 h post application scale formation.

Animals treated with the test substance in FCA showed 49 and 72 h after application severe erythema with injuries in the depth and strong oedema. The control animals showed comparable reaction at the application site.

 

- Results of the challenge application:

None of the test animals and none of the control animals showed a skin reaction 48 and 72 h post application.

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across based on grouping of substances (category approach)
Adequacy of study:
weight of evidence
Study period:
02 Dec 1991 - 03 Jan 1992
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study with acceptable restrictions
Remarks:
No data on reliability check (positive control).
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data on reliabilty check (positive control)
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
A non-LLNA test is available that was performed prior to the current data requirements, stipulated in Regulation (EC) No 1907/2006. In accordance with the same Regulation, the data was included to avoid unnecessary testing.
Species:
guinea pig
Strain:
other: Dunkin Hartley, Pirbright White Bor:DHPW [SPF]
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Age at study initiation: young adults
- Weight at study initiation: mean 425 g
- Housing: 5 animals of the same sex per cage in Makrolon IV cages.
- Diet: Ssniff G4 complete feed for guinea pigs (Ssniff Spezialfutter GmbH, Soest, Germany), ad libitum
- Water: drinking water (Gelsenwasser, Haltern, Germany), ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12
Route:
intradermal and epicutaneous
Vehicle:
other: maize germ oil MEH 56
Concentration / amount:
Intradermal induction: 10%
Epicutaneous induction: 100%
Day(s)/duration:
intradermal induction: single treatment; epicutaneous induction: 48 h
Adequacy of induction:
non-irritant substance, but skin pre-treated with 10% SDS
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
other: maize germ oil MEH 56
Concentration / amount:
100%
Day(s)/duration:
24 h
Adequacy of challenge:
other: concentration selected based on a preliminary range-finding study in which no irritation was observed
No. of animals per dose:
Preliminary study
2 animals intradermal group, 4 animals dermal administration
Main study
10 (controls), 20 (in test group)
Details on study design:
RANGE FINDING TESTS:
Intracutaneous administration: The following concentrations of the test substance were each injected intracutaneously on the left flank (which had been shared 2-3 h before) of two animals to determine the intracutaneous tolerability (0.25, 0.5, 1, 2.5, 5 and 10% in maize germ oil MEH 56). The intracutaneous reaction was assessed 24 h after administration.
Dermal administration: About 2-3 h before dermal administration, the fur was removed mechanically from the left and right flanks. The patches were each impregnated with 0.15 mL of the appropriate formulation of test substance and applied to the sheared area. Each animal received 2 patches on each flank, the patches were covered with an occlusive plaster and fixed with a bandage for 24 h (left flank, front 2.5%, back 25%; right flank, front 50%, right flank, back 100%). The patches were removed after 24 h, and the dermal reaction was assessed immediately after removal and 48 h and 72 h after administration.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: test substance in maize germ oil MEH 56
Injection 3: test substance in a 1:1 mixture (v/v) FCA/vehicle
Epicutaneous: test substance

- Control group 1:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: maize germ oil MEH 56
Injection 3: a 1:1 mixture (v/v) FCA/vehicle
Epicutaneous: maize germ oil MEH 56

- Control group 2:
Intradermal (3 pairs of injections):
Injection 1: a 1:1 mixture (v/v) FCA/water
Injection 2: maize germ oil MEH 56
Injection 3: a 1:1 mixture (v/v) FCA/vehicle
Epicutaneous: maize germ oil MEH 56

- Site: shoulder region (intradermal + epicutaneous)
- Frequency of applications: every 7 days
- Duration: Day 0-7
- Concentrations: intradermal 10%, epicutaneous 100%

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: Day 21
- Exposure period: 24 h
- Test groups: test substance
- Control group I: test substance
- Control group II: vehicle control is employed only in the induction treatment; no challenge with vehicle
- Site: right flank
- Concentrations: 100%
- Evaluation (hr after challenge): 24, 48 and 72 h

OTHER: 2-3 h before the dermal treatment the right flank of the test animals and of control group I was sheared.
The highest concentration of test substance administered dermally in the preliminary test caused no irritation of the skin. In order to cause slight to moderate inflammation of the skin for the dermal induction, one day before the dermal administration (Day 6) all the test and control animals were sheared on the shoulder and treated with sodium dodecyl sulphate (10% in Vaseline).

Scoring scheme for dermal reactions: Draize scoring system
Challenge controls:
The control group is actually a challenge control.
Positive control substance(s):
not specified
Remarks:
The sensitivity of the test system was reported to be checked at regular intervals (no further information).
Key result
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
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: other: negative control group I. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction: 10%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 10%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
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
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: other: negative control group I. Dose level: induction: 0%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 10.0.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 10%; challenge: 100%
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction: 10%; challenge: 100%. No with. + reactions: 0.0. Total no. in groups: 20.0.
Key result
Group:
positive control
Remarks on result:
other: The sensitivity of the test system was reported to be checked at regular intervals (no further information).

PRELIMINARY TEST

- Intracutaneous administration:

All test substance concentrations and the pure vehicle caused very slight erythema and well-defined oedema at the injection sites in both animals 24 h after the intradermal administration.

- Dermal administration:

None of the test substance concentrations (2.5, 25, 50 and 100%) caused dermal reactions 24, 48 and 72 h after administration, therefore the undiluted test substance was used for the dermal administration in the main test. Since the undiluted test substance had no irritant effect on the skin, pretreatment with sodium dodecyl sulphate (10% in Vaseline) was chosen to cause slight ot moderate inflammation of the skin in the dermal induction phase of the main test.

MAIN TEST

- Bodyweight changes and systemic effects:

No toxic effects were observed in the treated animals during the observation period.

 

- Intracutaneous and dermal induction:

1 h after intracutaneous injection of Freunds´s Adjuvant all the test and control animals showed severe erythema and severe oedema. After 24 h all the animals had severe erythema with deep damage and severe oedema. Injections of the test substance caused very slight to well-defined erythema and oedema in all the test animals 1 h and 24 h after administration. The injection sites treated only with maize germ oil MEH 56 showed very slight to well-defined erythema and oedema in all the control animals 1 h and 24 h after administration. The injection sites treated with the test substance in Freund´s Adjuvant showed very slight to moderate erythema and well-defined to moderately severe oedema in all test animals 1 h after administration. Severe erythema and severe oedema were observed in all animals after 24 h. Injection of FCA and the vehicle resulted in very slight to moderate erythema and well-defined to moderate oedema in all the control animals 1 h after administration. Severe erythema and severe oedema were observed 24 h later.

On Day 7 the shoulder region was distinctly reddened and swollen owing to the treatment with sodium dodecyl suphate the preceding day. After removal of the occlusive dressing, the skin showed schaling, and in some cases bleeding scratches, in all the test and control animals. 49 and 72 h after administration there was severe erythema with deep damage and severe oedema at the injection sites treated with FCA in all the test and control animals. There was well-defined erythema and oedema at the injection sites of the test substance and only with vehicle 49 h after administration. 24 h later, the skin showed scaling, reddening and swelling. There was severe erythema and severe oedema at the injection sites treated with 10% test substance in FCA 49 h after administration in 19/20 animals. 1/20 animals showed well-defined reddening and swelling. 9/20 animals also had deep damage. 72 h later, 19/20 animals had severe erythema with deep damage and severe oedema. One animal had moderate reddening and swelling. The sites of injection of FCA and the vehicle showed severe erythema and severe oedema in all control animals 49 h after administration. 10/20 animals showed deep damage at the injection sites. After 72 h all the animals had severe erythema with deep damage and severe oedema.

 

- Challenge treatments:

There were no signs of skin irritation in the administration area 48 and 72 h after administration either in the test animals or in the animals in control group I. 

Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

The hazard assessment is based on the data currently available. New studies with the registered substance and/or other member substances of the glycol esters category will be conducted in the future. The finalised studies will be included in the technical dossier as soon as they become available and the hazard assessment will be re-evaluated accordingly.

For further details, please refer to the category concept document attached to the category object (linked under IUCLID section 0.2) showing an overview of the strategy for all substances within the glycol esters category.

CAS 68583-51-7

No studies are available investigating the skin sensitising properties of Decanoic acid, mixed esters with octanoic acid and propylene glycol (CAS 68583-51-7). In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category members Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and Dodecanoic acid, ester with 1,2-propanediol (CAS 37321-62-3) was conducted.

The skin sensitising potential of the category members was investigated in Guinea pig maximisation tests according to EU method B.6 (Henkel 1989) and according to OECD guideline 406 under GLP conditions (Hüls AG, 1992a, b).

In the study with Myristic acid, monoester with propane-1,2-diol, a preliminary range finding test was conducted to evaluate the suitable concentrations for the main study for the intradermal injection and the patch testing. In the main study, 20 female Pirbright white guinea pigs were induced with a single intradermal injection of the test substance at 0.1% in Paraffin perliquid DAB 8 and an epicutaneous occlusive application of the test substance at 15% on the shoulder region 7 days later. A negative control group of 20 animals was treated with Paraffin perliquid DAB 8 only. Epicutaneous challenge exposure was conducted 20 days after the first induction for 24 h under occlusive conditions at concentrations of 2.5% and 5% of the test substance, respectively. All test and control animals showed no skin reactions after 24 and 48 h with one exception only. In one control animal, a slight redness of the skin after 48 h was apparent. No positive control data was included in the study report for reliability check (Henkel, 1989). In two studies with Butylene glycol dicaprylate / dicaprate and Dodecanoic acid, ester with 1,2-propanediol by Hüls AG (1992a, b) following preliminary range finding tests, male and female Dunkin Hartley guinea pigs (20 in test group, 10 in control group) were induced with a single intradermal injection of the test substance at 10% in maize germ oil MEH56 or corn oil, respectively. Epicutaneous occlusive application of the undiluted test substance was performed 7 days later. The negative control groups were treated with maize germ oil MEH56 or corn oil, respectively. Epicutaneous challenge exposures were conducted 20 days after the first induction for 24 h under occlusive conditions. The undiluted test substance was applied on the right flank and evaluation of skin reactions was carried out 24, 48 and 72 h after application. After intradermal injection of Freund´s adjuvans and test substance or vehicle only, all test and control animals showed severe erythema and oedema after 24 h. After challenge, all test and control animals showed no skin reactions after 24, 48 and 72 h. The sensitivity of the test system was reported to be checked at regular intervals; however, the data were not included in the study reports (Hüls AG, 1992a, b).

In summary, based on the available data on the skin sensitisation properties of the category members, it is concluded, that there is no evidence of sensitising properties of Decanoic acid, mixed diesters with octanoic acid and propylene glycol.

CAS 627-83-8

One study investigating the skin sensitising potential of ethylene distearate (CAS No. 627-83-8) is available.
The study was performed according to a Buehler test protocol similar to OECD guideline 406 in Hartley guinea pigs (IBR Forschungs GmbH, 1982). The solid test material was mixed with a few drops of water and applied at a concentration of 100% for epidermal induction and challenge. The negative control group was treated with the vehicle only. No positive control data was included in the study report for reliability check. At challenge, the neat test substance induced no skin effects in the test and negative control group. No further skin reactions after induction and challenge were observed. In addition, a sensitisation study with guinea pigs with limited details is available (HPV, 1982). Two animals were intradermally induced and challenged with 0.1% glycol distearate in a saline solution and showed no skin reactions (HPV, 1982).

In summary, based on all available data, ethylene distearate is not sensitising.

 

CAS 84988-75-0

No studies are available investigating the skin sensitising properties of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol. In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category members Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and ethylene distearate (CAS 627-83-8) was conducted. The studies of the category members are already discussed under the CAS number 68583-51-7 and CAS number 627-83-8.

The available studies investigating the sensitisation properties of the category members consistently showed negative results. Thus, there is no evidence for sensitising properties of Fatty acids, C14-18 and C16-18-unsatd., esters with propylene glycol.

 

CAS 624-03-3

No studies are available investigating the skin sensitising properties of ethane-1,2-diyl palmitate. In order to fulfil the standard information requirements set out in Annex VII, 8.3, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006 read-across from the structurally related category member ethylene distearate (CAS 627-83-8) was conducted. The studies of the category member ethylene distearate are already discussed under the respective CAS number.

The available studies investigating the sensitisation properties of ethylene distearate consistently showed negative results. Based on the available data on skin sensitisation properties of the category member, it is concluded, that there is no evidence for sensitising properties of ethane-1,2-diyl palmitate.

Additional data

In addition, the category members Glycol Stearate (CAS 111-60-4) and Fatty acids, C18 and C18 unsatd. epoxidized, ester with ethylene glycol (CAS 151661-88-0) did not show skin sensitisation properties, as well.

Conclusion for skin sensitisation properties

In conclusion, no skin sensitisation properties of the category members Ethylene distearate (CAS 627-83-8), Myristic acid, monoester with propane-1,2-diol (CAS 29059-24-3), Butylene glycol dicaprylate / dicaprate (CAS 853947-59-8) and Dodecanoic acid, ester with 1,2-propanediol (CAS 37321-62-3) were apparent in several in vivo studies. Altogether, the available data were consistently negative and thus there is no evidence for skin sensitisation properties of any category member of the Glycol Ester group.

 

References

Agency for Toxic Substances and Disease Registry (ATSDR) (1997): Toxicological Profile for Propylene Glycol. US Department of Health and Human Services. Atlanta, US.

Agency for Toxic Substances and Disease Registry (ATSDR) (2010): Toxicological Profile for Ethylene Glycol. US Department of Health and Human Services. Atlanta, US.

Gubicza, L., Kabiri-Badr, A., Keoves, E., Belafi-Bako, K. (2000): Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

Heymann, E. (1980): Carboxylesterases and amidases. In: Jakoby, W.B., Bend, J.R. & Caldwell, J., eds., Enzymatic Basis of Detoxication, 2nd Ed., New York: Academic Press, pp. 291-323.Gubicza, L. et al. (2000). Large-scale enzymatic production of natural flavour esters in organic solvent with continuous water removal. Journal of Biotechnology 84(2): 193-196.

International Programme on Chemical Safety (IPCS) (2001): Ethylene Glycol. Poisons Information Monograph. PIM 227.

Lilja, J. et al. (2005). Esterification of propanoic acid with ethanol, 1-propanol and butanol over a heterogeneous fiber catalyst. Chemical Engineering Journal, 115(1-2): 1-12.

Liu, Y. et al. (2006). A comparison of the esterification of acetic acid with methanol using heterogeneous versus homogeneous acid catalysis. Journal of Catalysis 242: 278-286.

Miller, O.N., Bazzano, G. (1965): Propanediol metabolism and its relation to lactic acid -metabolism. Annals of the New York Academy of Sciences 119, 957-973.

Radzi, S.M. et al. (2005). High performance enzymatic synthesis of oleyl oleate using immobilised lipase from Candida antartica. Electronic Journal of Biotechnology 8: 292-298.

Ritchie, A.D. (1927): Lactic acid in fish and crustacean muscle. Journal of Experimental Biology 4, 327-332.

Stryer, L. (1994): Biochemie. 2nd revised reprint, Heidelberg; Berlin; Oxford: Spektrum Akad. Verlag.

Tocher, D.R. (2003): Metabolism and Functions of Lipids and Fatty Acids in Teleost Fish. Reviews in Fisheries Science 11(2), 107-184.

WHO (2002): Ethylene Glycol: Human Health Aspects. Concise International Chemical Assessment Document 45.

Zhao, Z. (2000). Synthesis of butyl propionate using novel aluminophosphate molecular sieve as catalyst. Journal of Molecular Catalysis 154(1-2): 131-135.


Justification for selection of skin sensitisation endpoint:
Hazard assessment is conducted means of read-across based on a category approach. All available studies are adequate and reliable based on the identified similarities in structure and intrinsic properties between source and target substances and overall quality assessment (refer to the endpoint discussion for further details).

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

This information is not available.


Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII-X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

According to Article 13 of Regulation (EC) No. 1907/2006 "General Requirements for Generation of Information on Intrinsic Properties of substances", information on intrinsic properties of substances may be generated by means other than tests e.g. from information from structurally related substances (grouping or read-across), provided that conditions set out in Annex XI are met. Annex XI, "General rules for adaptation of this standard testing regime set out in Annexes VII to X” states that “substances whose physicochemical, toxicological and ecotoxicological properties are likely to be similar or follow a regular pattern as a result of structural similarity may be considered as a group, or ‘category’ of substances. This avoids the need to test every substance for every endpoint". Since the group concept is applied to the members of the Glycol Ester Category, data will be generated from representative reference substance(s) within the category to avoid unnecessary animal testing. Additionally, once the group concept is applied, substances will be classified and labeled on this basis.

Therefore, based on the group concept, all available data on sensitisation do not meet the classification criteria according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.