Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

The skin sensitisation potential of the substance was investigated according to OECD Guideline 406 in a Guinea Pig Maximisation Test. None of the 10 animals of the test group showed allergic skin reactions until 72 hours after patch removal.

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:
from 1998-09-21 to 1998-10-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The test was performed prior to the introduction of the obligation to use the LLNA method.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: approx. 4 - 5 weeks
- Weight at study initiation: 301 - 311 g
- Housing: animals were kept in groups (max. group size 10 animals) in Terluran - cages on Altromin saw fiber bedding
- Diet (e.g. ad libitum): Altromin 3122 maintenance diet for guinea pigs ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: not mentioned


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 1998-09-21 To: 1998-10-16
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
Day(s)/duration:
24 h
No. of animals per dose:
10 animals in the test group, 5 in control group
Details on study design:
RANGE FINDING TESTS: Four animals were topically treated with the test item. No signs of irritation were recorded after a contact period of 24 h. Therefore the maximum concentration was chosen for the inductions and the challenge.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st exposure: intracutaneous injections (0.1 mL); 2nd exposure: epicutaneous for 48 hours
- Site: according to guideline
- Frequency of applications: day 0: intradermal treatment, day 6: pretreatment with sodium lauryl sulphate (0.5 mL, 10% in vaseline) and day 7: dermal treatment
- Duration: 20 days
- Concentrations:
Induction, 1st stage:
Test group: Injection 1: Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline; injection 2: test item 100%; injection 3: test item 50% (v/v) in Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline
Control group: Injection 1: Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline; injection 2: NaCL (0.9%); injection 3: NaCl (0.9%) 50% (v/v)in Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline
Induction, 2nd stage:
Test group: 100% test item
Control group: 100% NaCl (0.9%)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 20
- Exposure period: 24 hours
- Test group: test item and NaCl (0.9%) as intraspecific control
- Control group: same as test group
- Site: left flanks for test substance, right flanks for NaCl
- Concentrations: 100%
- Evaluation: 24, 48 and 72 h after patch removal
Challenge controls:
see above
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole (reliability check, not in parallel with the test)
Positive control results:
60% of the positive control animals showed sensitization reactions 24 and 48 hours after end of challenge treatement (positive cotnrol substance concentrations: 2% at induction I phase, 25% at induction II phase, 15% at challenge)
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No other signs of toxicity observed, animals showed normal food intake and weight gain.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No other signs of toxicity observed, animals showed normal food intake and weight gain..
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No other signs of toxicity observed, animals showed normal food intake and weight gain.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No other signs of toxicity observed, animals showed normal food intake and weight gain..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
None of the 10 animals of the test group showed allergic skin reactions until 72 hours after patch removal as compared to the intraspecific application of NaCl (0.9%) and to the animals of the control group. The sensitization rate after application of Tri (hexy, octy, decyl) citrate was 0%. Under the test contions described the test item showed no sensitizing properties.
Executive summary:

The skin sensitisation potential of the substance was investigated according to OECD Guideline 406 in a Guinea Pig Maximisation Test. None of the 10 animals of the test group showed allergic skin reactions until 72 hours after patch removal as compared to the intraspecific application of NaCl (0.9%) and to the animals of the control group. The sensitization rate after application of Tri (hexy, octy, decyl) citrate was 0%. Under the test contions described the test item showed no sensitizing properties.

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:
from 1998-09-21 to 1998-10-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
1. HYPOTHESIS FOR THE ANALOGUE APPROACH
This read across is based on the hypothesis that source and target substance have similar toxicological and ecotoxicological properties, because
- they are manufactured from similar/identical precursors under similar conditions
- they share structural similarities with common functional groups: ester bonds and fatty alcohol chains varying in length

Therefore, read across from the existing physical-chemical, toxicological and ecotoxicological studies on the source substance is considered as an appropriate adaptation to the standard information requirements of the REACH Regulation for the target substance , in accordance with the provisions of Annex XI, 1.5 of the REACH Regulation.

2. SOURCE AND TARGET CHEMICAL(S) (INCLUDING INFORMATION ON PURITY AND IMPURITIES)
The source substance 2-Hydroxypropan-1,2,3-tricarboxylic acid, tri (hexyl, octyl, decyl esters) is a UVCB substance manufactured from 2-Hydroxypropan-1,2,3-tricarboxylic acid and C6-10 fatty alcohols.
The target substance Reaction mass of didodecyl hydrogen citrate and tridodecyl 2-hydroxypropane-1,2,3-tricarboxylate is a multi constituent substance manufactured from 2-Hydroxypropan-1,2,3-tricarboxylic acid and 1-dodecyl alcohol.


3. ANALOGUE APPROACH JUSTIFICATION
The read-across hypothesis is based on structural similarity of the target and source substance. Based on available experimental data, including key physicochemical properties and a genotoxicity study, the read-across strategy is supported by a similar toxicological profile of the target and source substance.
The respective reliable data (RL 1 or 2) are summarized in the data matrix; robust study summaries are included in the Technical Dossier in the respective sections.
The read-across from the source substance is justified:
a) Based on the information given in section 1, it can be concluded that the substances are similar in structure, since they are manufactured from similar or identical precursors under similar conditions and all contain the same functional groups. Thus a common mode of action can be assumed.
c) The only difference within the two substances is a (minor) variation in the chain length of the alcohols used for manufacture, which is not expected to have a relevant impact on intrinsic toxic or ecotoxic activity and environmental fate.

4. DATA MATRIX
See document under "Attached justification".
Reason / purpose for cross-reference:
read-across source
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Winkelmann GmbH, Borchen, Germany
- Age at study initiation: approx. 4 - 5 weeks
- Weight at study initiation: 301 - 311 g
- Housing: animals were kept in groups (max. group size 10 animals) in Terluran - cages on Altromin saw fiber bedding
- Diet (e.g. ad libitum): Altromin 3122 maintenance diet for guinea pigs ad libitum
- Water (e.g. ad libitum): drinking water ad libitum
- Acclimation period: not mentioned


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 1998-09-21 To: 1998-10-16
Route:
intradermal and epicutaneous
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
100 %
Day(s)/duration:
24 h
No. of animals per dose:
10 animals in the test group, 5 in control group
Details on study design:
RANGE FINDING TESTS: Four animals were topically treated with the test item. No signs of irritation were recorded after a contact period of 24 h. Therefore the maximum concentration was chosen for the inductions and the challenge.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: 1st exposure: intracutaneous injections (0.1 mL); 2nd exposure: epicutaneous for 48 hours
- Site: according to guideline
- Frequency of applications: day 0: intradermal treatment, day 6: pretreatment with sodium lauryl sulphate (0.5 mL, 10% in vaseline) and day 7: dermal treatment
- Duration: 20 days
- Concentrations:
Induction, 1st stage:
Test group: Injection 1: Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline; injection 2: test item 100%; injection 3: test item 50% (v/v) in Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline
Control group: Injection 1: Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline; injection 2: NaCL (0.9%); injection 3: NaCl (0.9%) 50% (v/v)in Freund's Adjuvant complete, 1+1 (v/v) diluted with isotonic saline
Induction, 2nd stage:
Test group: 100% test item
Control group: 100% NaCl (0.9%)

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: on day 20
- Exposure period: 24 hours
- Test group: test item and NaCl (0.9%) as intraspecific control
- Control group: same as test group
- Site: left flanks for test substance, right flanks for NaCl
- Concentrations: 100%
- Evaluation: 24, 48 and 72 h after patch removal
Challenge controls:
see above
Positive control substance(s):
yes
Remarks:
Mercaptobenzothiazole (reliability check, not in parallel with the test)
Positive control results:
60% of the positive control animals showed sensitization reactions 24 and 48 hours after end of challenge treatement (positive cotnrol substance concentrations: 2% at induction I phase, 25% at induction II phase, 15% at challenge)
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No other signs of toxicity observed, animals showed normal food intake and weight gain.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No other signs of toxicity observed, animals showed normal food intake and weight gain..
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No other signs of toxicity observed, animals showed normal food intake and weight gain.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No other signs of toxicity observed, animals showed normal food intake and weight gain..
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
100 %
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 100 %. No with. + reactions: 0.0. Total no. in groups: 5.0.
Interpretation of results:
not sensitising
Remarks:
Migrated information
Conclusions:
None of the 10 animals of the test group showed allergic skin reactions until 72 hours after patch removal as compared to the intraspecific application of NaCl (0.9%) and to the animals of the control group. The sensitization rate after application of Tri (hexy, octy, decyl) citrate was 0%. Under the test contions described the test item showed no sensitizing properties.
Executive summary:

The skin sensitisation potential of the substance was investigated according to OECD Guideline 406 in a Guinea Pig Maximisation Test. None of the 10 animals of the test group showed allergic skin reactions until 72 hours after patch removal as compared to the intraspecific application of NaCl (0.9%) and to the animals of the control group. The sensitization rate after application of Tri (hexy, octy, decyl) citrate was 0%. Under the test contions described the test item showed no sensitizing properties.

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

Justification for classification or non-classification

The skin sensitisation potential of the substance was investigated according to OECD Guideline 406 in a Guinea Pig Maximisation Test. None of the 10 animals of the test group showed allergic skin reactions until 72 hours after patch removal.