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Administrative data

Description of key information

Data on the main component of the reaction mass:

GPMT test on C16MES: negative

LLNA test on C16MES: negative

Data on a similar substance with a lower alkyl chain length:

GPMT test on C14MES: negative

LLNA test on C14MES: negative

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:
experimental study
Adequacy of study:
key study
Study period:
24 June- 25 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
see below
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
In the preliminary study for the determination of the maximum concentration causing a slight to moderate irritation by cutaneous application: by mistake, the filter paper saturated with the formulated test substance was held in place for 48 hrs using Elastplaste semi-occlusive dressing instead of Blenderm 3M (5 cm width) occlusive dressing made up of surgical tape.
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The GPMT test was performed in 2003 before the LLNA test was performed in 2005.
Species:
guinea pig
Strain:
Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories France
- Age at study initiation: no data
- Weight at study initiation: 392.7 +/- 8.6 g for the control males and 393.4 +/- 4.1 g for the treated males.
- Housing: five males per treatment group in a cage of standard size
- Diet (e.g. ad libitum): daily at fixed times
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days before the preliminary study and 6 days before the main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 45-65
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
2% and 5%
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
2% and 5%
No. of animals per dose:
10
Details on study design:
PRELIMINARY TESTS:
- determination of the maximum concentration causing a slight to moderate irritation by intradermal injection of 0.1 mL in the retro-scapular region at 6 sites.
- Determination of the maximum concentration causing a slight to moderate irritation by cutaneous application of 0.2 mL over an area of 8 cm^2, using one concentration on each flank (5 w/v% and 2 w/v%).
- Determination of the Maximum Non-irritant Concentration by cutaneous application.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: Intradermal induction on Day 1 and topical induction on Day 8
- Exposure period: Day 1 and Day 8
- Test groups: 10 males
- Control group: 10 males
- Site:
Site 1: 2 injections of 0.1 ML of complete Freund's adjuvant diluted 50% in sterile and pyrogenfree isotonic sodium chloride solution.
Site 2: 2 injections of 0.1 mL of Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt formulated at 0.1 w/v%
Site 3: 2 injections of 0.1 mL of an emulsion of equal volume of complete Freund's adjuvant diluted 50% in sterile and pyrogenfree isotonic sodium chloride solution and of fomulated Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt. The final concentration of fomulated Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt injected was the same as used for site 2.
- Frequency of applications: second induction with 0.2 mL of Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt formulated at 5 w/v% by cutaneous application on a piece of filter paper, held in place for 48 hrs using an occlusive dressing.

B. CHALLENGE EXPOSURE
- No. of exposures: one
- Day(s) of challenge: on Day 22
- Exposure period: 24 hrs
- Test groups: 10 males/treatment
- Control group: 10 males
- Site: the right flank region over 2 areas of approx. 4 cm^2
- Concentrations: 0.1 mL of Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt formulated at 5 w/v% and 2 w/v% on an occlusive dressing.
- Evaluation (hr after challenge): approx 24 hrs and 48 hrs after removal of the dressing

Challenge controls:
Negative control animals received 0.1 mL of formulated Hexadecanoic acid, 2-sulfo-, 1-methylester, sodium salt at MNIC (2 w/v%) and the lower concentration chosen by the sponsor.
The positive control animals received 0.1mL of 1% DNCB solution.
Positive control substance(s):
yes
Remarks:
dinitrochlorobenzene (DNCB, 1% in alcoholic solution)
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
not specified
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
not specified
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
not specified
No. with + reactions:
10
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
not specified
No. with + reactions:
10
Total no. in group:
10

- No mortallity occurred throughout the study

- Behaviour of the animals treated with the test substance was normal and was not different from that of the control group.

- Mean body weight gain in animals treated with the test substance did not differ significantly from that of animals of the negative control group.

- Skin reactions: evaluation of local irritation: no irritation reaction was noted at times 24 and 48 hrs in animals of the negative control group and in animals treated during the challange phase with the test substance at the MNIC and at the lower concentration.

- the maximum slight to moderate irritant concentration by intradermal administration was 0.1 w/v% of formulated test substance

- The maximum non-irritant concentration (MNIC) determined by epicutaneous application was 2 w/v% of formulated test substance.

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions adopted, the test substance showed no allergenicity at 24 and 48 hours. It is thus considered that the test substance is free of any sensitising capacity in the male guinea pig.
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
24 June - 25 July 2003
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
see below
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Principles of method if other than guideline:
In the preliminary study for the determination of the maximum concentration causing a sklight to moderate irritation by cutaneous application: by mistake, the filter paper saturated with the formulated test substance was held in place for 48 hrs using Elastplaste semi-occlusive dressing instead of Blenderm 3M (5 cm width) occlusive dressing made up of surgical tape.
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
other: Albino Hartley
Sex:
male
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
2% and 5%
Route:
epicutaneous, semiocclusive
Vehicle:
water
Concentration / amount:
2% and 5%
No. of animals per dose:
10
Details on study design:
RANGE FINDING TESTS:


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 14 days
- Site: shoulder
- Frequency of applications: 2
- Concentrations: 0.1% on day 0 by intradermal injection and on day 7 a 48hr filter paper induction patch containing 5% to the injection site.


B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: 1
- Site: the flank of the animals
- Concentrations: after 14 days, 5% and 2% were applied on filter paper as a 24hr occlusive patch
- Evaluation (hr after challenge): 24 and 48 hrs


Positive control substance(s):
yes
Remarks:
1% dinitrochlorobenzene (DNCB) in alcoholic solution
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
2%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
normal
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
No. with + reactions:
10
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
No. with + reactions:
10
Total no. in group:
10

- No mortallity occurred throughout the study

- Behaviour of the animals treated with the test substance was normal and was not different from that of the control group.

- Mean body weight gain in animals treated with the test substance did not differ significantly from that of animals of the negative control group.

- Skin reactions: evaluation of local irritation: no irritation reaction was noted at times 24 and 48 hrs in animals of the negative control group and in animals treated during the challange phase with the test substance at the MNIC and at the lower concentration.

- the discrete irritant concentration by intradermal administration was 0.1 w/v% of formulated test substance

- The maximum non-irritant concentration (MNIC) determined by epicutaneous application was 2 w/v% of formulated test substance.

- The non-irrative and practically dosable maximum concentration based on the results of the first epicutaneous apllication was 5w/v%

Interpretation of results:
GHS criteria not met
Conclusions:
Under the experimental conditions adopted, the test substance showed no allergenicity at 24 and 48 hours. It is thus considered that the test substance is free of any sensitising capacity in the male guinea pig.
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
supporting study
Study period:
March 12 - 17, 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
The study was perrformed according to OECD guidelines, but not much information was given on materials and methods. The study was not performed under GLP. The study does not contain a positive control in order to demonstrate appropriate performance of the assay. However, the test laboratory has historic positive control data available to show consistency of a satisfactory response over an extended period.
GLP compliance:
no
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: not indicated
- Housing: not indicated
- Diet (e.g. ad libitum): not indicated
- Water (e.g. ad libitum): not indicated
- Acclimation period: not indicated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not indicated
- Humidity (%): not indicated
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): not indicated
Vehicle:
dimethylformamide
Concentration:
5%, 10% and 25%
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: no data
- Lymph node proliferation response: no data


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Murine local lymph node assay (LLNA)
- Criteria used to consider a positive response: a proliferative response exceeding SI=3


TREATMENT PREPARATION AND ADMINISTRATION:
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Statistics:
Not performed.
Positive control results:
Periodical verification of the LLNA study is performed at the testing laboratory.
2002 April 16: SI = 4.6 at 25% v/v
2003 April 22: SI = 7.0 at 20% v/v
2003 June 5: SI = 8.7 at 25% v/v
Parameter:
SI
Value:
1.3
Test group / Remarks:
5%
Parameter:
SI
Value:
2.2
Test group / Remarks:
10%
Parameter:
SI
Value:
2.9
Test group / Remarks:
25%
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: For the vehicle (DMF): mean value of 299.4 For the 5%: mean value of 398.0 For the 10%: mean value of 668.1 For the 25%: mean value of 877.6

No proliferative response exceeding an SI=3 was observed following treatment at the highest concentration (25%) of C14-MES, but there was an indication of a dose-response trend.

Interpretation of results:
GHS criteria not met
Conclusions:
C14-MES was considered to be negative for skin sensitization in the LLNA under the testing conditions conducted.
Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 12 - 17, 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
The study was performed according to OECD guidelines, but not much information was given on materials and methods. The study was not performed according to GLP. The study does not contain a positive control in order to demonstrate appropriate performance of the assay. However, the test laboratory has historic positive control data available to show consistency of a satisfactory response over an extended period.
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
not specified
GLP compliance:
no
Type of study:
mouse local lymph node assay (LLNA)
Species:
mouse
Strain:
other: CBA/J
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc
- Age at study initiation: 9-10 weeks old
- Weight at study initiation: not indicated
- Housing: not indicated
- Diet (e.g. ad libitum): not indicated
- Water (e.g. ad libitum): not indicated
- Acclimation period: not indicated


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not indicated
- Humidity (%): not indicated
- Air changes (per hr): not indicated
- Photoperiod (hrs dark / hrs light): not indicated


IN-LIFE DATES: From 12 to 17 March 2003
Vehicle:
dimethylformamide
Concentration:
5%, 10% and 25%
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: no data
- Irritation: no data
- Lymph node proliferation response: no data


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: Murine local lymph node assay (LLNA)
- Criteria used to consider a positive response: a proliferative response exceeding SI=3


TREATMENT PREPARATION AND ADMINISTRATION:
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)
Positive control results:
Periodical verification of the LLNA study is performed at the testing laboratory.
2002 April 16: SI = 4.6 at 25% v/v
2003 April 22: SI = 7.0 at 20% v/v
2003 June 5: SI = 8.7 at 25% v/v
Parameter:
SI
Value:
1.1
Test group / Remarks:
5%
Parameter:
SI
Value:
2.2
Test group / Remarks:
10%
Parameter:
SI
Value:
1.4
Test group / Remarks:
25%
Parameter:
other: disintegrations per minute (DPM)
Remarks on result:
other: For the vehicle (DMF): mean value of 299.4 For the 5%: mean value of 338.1 For the 10%: mean value of 671.0 For the 25%: mean value of 405.5

No proliferative response exceeding an SI=3 was observed following treatment at the highest concentration (25%) of C16-MES, nor was there any indication of a dose-response trend.

Interpretation of results:
GHS criteria not met
Conclusions:
C16-MES was considered to be negative for skin sensitization in the LLNA under the testing conditions conducted.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

In a guinea pig maximisation test, performed according to OECD 406 and EU B.6 test guidelines, no sensitisation potential 24 and 48 hours after challenge was noted with 2 and 5% C16MES. In an LLNA study, performed according to OECD 429 test guidelines, mice treated with 5, 10 and 25% of C16MES did not show an SI-index higher than 3. Based on these results the substance is considered not sensitising. In addition, data with C14MES are available from a GPMT study and an LLNA study. Both studies showed a negative result. No data is available on sensitization potential with the second component of the reaction mass C18MES. However, based on the data on the main component C16MES and the comparable substance C14MES, it is judged that C18MES will also have a negative result for sensitization. As a consequence, the reaction mass is also judged to have no sensitizing potential.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Respiratory sensitisation was not examined.

Justification for classification or non-classification

The reaction mass has no potential sensitising properties and thus does not have to be classified according to CLP Regulation 1272/2008.