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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
25 August 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP study conducted according to a recognised guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
The mice in the main study were not weighed on arrival in error and were weighed the day after arrival as soon as this error was discovered. This deviation was considered to have not affected the integrity or validity of the study.
Qualifier:
according to guideline
Guideline:
EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)
Deviations:
yes
Remarks:
The mice in the main study were not weighed on arrival in error and were weighed the day after arrival as soon as this error was discovered. This deviation was considered to have not affected the integrity or validity of the study.
GLP compliance:
yes (incl. QA statement)
Type of study:
mouse local lymph node assay (LLNA)

Test material

Constituent 1
Chemical structure
Reference substance name:
(2R)-2-methyloctane-1,8-diamine; (2S)-2-methyloctane-1,8-diamine
EC Number:
700-111-0
Cas Number:
148528-05-6
Molecular formula:
C9H22N2
IUPAC Name:
(2R)-2-methyloctane-1,8-diamine; (2S)-2-methyloctane-1,8-diamine
Details on test material:
- Name of test material (as cited in study report): MODA (2-methyl-1,8-octanediamine)
- Substance type: monomer for polymer production
- Physical state: liquid
- Analytical purity: 98.9% (GC)
- Impurities (identity and concentrations): not stated in report
- Purity test date: not stated in report
- Lot/batch No.: 93328
- Expiration date of the lot/batch: October 2009
- Stability under test conditions: not stated in report
- Storage condition of test material: room temperature
- Other:

In vivo test system

Test animals

Species:
mouse
Strain:
CBA
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan UK Ltd
- Age at study initiation: Approximately eight to twelve weeks (at dosing on Day 1)
- Weight at study initiation: 16.9 - 21.1 g
- Housing: individually in polycarbonate cages with woodflake bedding
- Diet (e.g. ad libitum): free access to a standard rodent diet (Rat and Mouse No. 1 Maintenance Diet)
- Water (e.g. ad libitum): potable water, freely available, from the public supply
- Acclimation period: at least five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 - 23
- Humidity (%): 40 - 70
- Air changes (per hr): not stated in report
- Photoperiod (hrs dark / hrs light): 12 hours continuous artificial light and twelve hours continuous dark in each 24 period


IN-LIFE DATES: From: 30 June 2009 To: 28 July 2009

Study design: in vivo (LLNA)

Vehicle:
dimethylformamide
Concentration:
1, 2.5 or 5% v/v
No. of animals per dose:
4
Details on study design:
RANGE FINDING TESTS:
- Compound solubility: MODA formed a clear colourless liquid at 50% in dimethylformamide
- Irritation: No signs of irritation were seen over the dosed area during the study, however underactive behaviour and partially closed eyelids were observed approximately 3 hours post dose on Day 3 (10% v/v). No signs of ill health, toxicity or irritation were seen during the study (5% v/v).
- Lymph node proliferation response: not investigated


MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Name of test method: animals were assigned without conscious bias
- Criteria used to consider a positive response: not stated in report

TREATMENT PREPARATION AND ADMINISTRATION: Groups or one female were treated with one concentration of the test substance. Each mouse
was treated by daily application of 25 µl of appropriate concentration of the test substance to the dorsal surface of each ear for three consecutive days (Days 1-3). The test substance was applied to the dorsal surface of each ear using an automatic micropipette. The test substance was spread over the entire dorsal surface of the ear using the tip of the pipette
Positive control substance(s):
hexyl cinnamic aldehyde (CAS No 101-86-0)

Results and discussion

Positive control results:
A loss in bodyweight was recorded for one female receiving the positive control during the study

In vivo (LLNA)

Resultsopen allclose all
Key result
Parameter:
SI
Value:
4.8
Test group / Remarks:
1% v/v MODA
Key result
Parameter:
SI
Value:
5.3
Test group / Remarks:
2.5% v/v MODA
Remarks on result:
other: Interpretation of results The test substance is regarded as a sensitizer if at least one concentration of the test substance results in a three-fold greater increase in 3HTdR incorporation compared to control values.
Parameter:
other:
Value:
0
Remarks on result:
other: Disintegrations per minute are less background count of 44.15 dpm
Parameter:
SI
Value:
0
Test group / Remarks:
5% v/v MODA

Any other information on results incl. tables

 


Preliminary investigation


Mortality and clinical signs: There were no deaths observed during this study. However the following observations were noted: Group 1 (10% v/v): No signs of irritation were seen over the dosed area during the study, however underactive behaviour and partially closed eyelids were observed approximately 3 hours post dose on Day 3. Group 2 (5% v/v): No signs of ill health, toxicity or irritation were seen during the study.


Bodyweight: Bodyweight increases were recorded for both mice over the period of the study. On the basis of the results from the preliminary investigation, 5% v/v was considered a suitable high dose level for the main phase of the study.


 


Main phase


Mortality and clinical signs:There were no deaths and no signs of ill health or toxicity were observed during this study. However the following observations were noted: Wet or greasy fur was noted for all control and test animals post-dose from Day 1 or 2 and white dose residue on the ears was noted for one mouse dosed at 1% v/v and all animals dosed at 5% v/v. These signs had resolved completely in all animals by termination.


Bodyweight:A loss in bodyweight was recorded for one female receiving the positive control during the study. All other animals gained weight during the study.


Estimation of the proliferative response of lymph node cells:The test/control ratios obtained for 1, 2.5 and 5% v/v MODA were 4.8, 5.3 and 0.0 respectively. As a test/control ratio of 3 or more was recorded for two of the concentrations tested, MODA was considered to have the potential to cause skin sensitization (delayed contact hypersensitivity). The low result obtained for 5% v/v MODA is unusual, however as the regulatory guidelines state that the test material must be labelled as a potential skin sensitizer if any of the tested dose levels have a positive result, this result does not affect the conclusion of this study.


 


Group dpm/node and test control ratios


 














































































Group



Concentration


% v/v



dpm



Number of lymph nodes per group



dpm/node



Test/control ratio*



Result


+ = positive


- = negative



 



 



 



 



 



 



 



3



DMF



1174.55



8.0



146.82



n/a



n/a



4



1



5659.45



8.0



707.43



4.8



+



5



2.5



6227.95



8.0



778.49



5.3



+



6



5



28.65



8.0



3.58



0.0



-



7



HCA 25% v/v



16090.45



8.0



2011.31



13.7



+



 



 



 



 



 



 



 



*       Test/control (SI) of 3 or greater indicates a positive result 


n/a       not applicable


dpm       Disintegrations per minute (less background count of 44.15 dpm)


DMF       Dimethylformamide (vehicle control)


HCA hexyl cinnamic aldehyde (positive control)

Applicant's summary and conclusion

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
MODA is to be regarded as a potential skin sensitizer

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