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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

Data from OECD 406 guideline studies on two structural analogues, MI3 and X14DesB30 indicate no potential for skin sensitisation. Due to very close structural similarity to Insulin aspart precusor, a lack of skin sensitising potential can be concluded for Insulin aspart precusor as well.

See further read-across justification in document attacthed in section 13.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
read-across source
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
90% S2 / 0.5 ml S3
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No signs of ill health or toxicity were observed
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
90% S1 / 0.5 ml 2
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No signs of ill health or toxicity were observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
Data from OECD 406 guideline studies on MI3 and X14DesB30 indicate no potential for skin sensitisation. Due to very close structural similarity to Insulin aspart precusor, a lack of skin sensitising potential can be concluded for Insulin aspart precusor as well.
See further read-across justification in document attacthed in section 13.
Executive summary:

No data is available for insulin aspart precurser.

Data from OECD 406 guideline studies on MI3 and X14DesB30 indicate no potential for skin sensitisation. Due to very close structural similarity to Insulin aspart precusor, a lack of skin sensitising potential can be concluded for Insulin aspart precusor as well.

See further read-across justification in document attacthed in section 13.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Buehler method
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000.09.04 - 2000.10.20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
In vivo data for MI3 skin sensitization to the guinea-pig was allready avalible prior initiating this registration dossier.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: MI3, CHD NO. 0179/00-0665 Lot 2, Batch number: C202493
- Expiration date of the lot/batch: December 2000
- Purity 98.67 % (295 mg active sub/g crude sub)
- Purity test date: 2000.07.13

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: - 20 degrees celsius, in the dark.
- Stability under test conditions: NA
- Solubility and stability of the test substance in the solvent/vehicle: up to 90 % w/v in water.


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Fresh prepared smooth brown paste (90 %w/v) using water on the day of exposure
- Final preparation of a solid: Freshly prepared smooth brown paste (90 %w/v) using water on the day of exposure

FORM AS APPLIED IN THE TEST (if different from that of starting material) freshly prepared paste (*90 %w/v) using water as vehicle.

:
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dunkin/Hartley, albino
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Microbiological status of animals, when known: NA
- Age at study initiation: 5 - 8 weeks old.
- Weight at study initiation: 351 - 427g
- Housing: groups of five animals in suspended metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum, vitamin C enriched guinea pig diet.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: five days
- Indication of any skin lesions: NA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24 degree celsius
- Humidity (%): 30 - 70 %
- Air changes (per hr): NA
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12hrs light
- IN-LIFE DATES: From: To: 2000.09.04 - 2000.10.20
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
MI3, 90% w/v in sterile water
Day(s)/duration:
on Days 1, 8 and 15.
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
MI3, 90% w/v in sterile water
Day(s)/duration:
Challange two weeks after the final induction and examinations after 24 and 48 hours.
Adequacy of challenge:
other: the maximum practical concentration that could be prepared and dosed topically and not given rise to irritating effects.
No. of animals per dose:
Control animals (n=10).
Test animals (n=20).
Preliminary investigations (n=4).
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: Day 1, Day 8 and Day 15.
- Test groups: MI3 exposure, 20 animals
- Control group: Vehicle (sterile water) exposure, 10 animals
- Site: Left shoulder region
- Frequency of applications: 3 times
- Duration: 6 hours
- Concentrations: 90% w/v in sterile water

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Two weeks after final induction
- Exposure period: 6 hours
- Test groups: MI3 exposure, 20 animals
- Control group: Exposured as test group, 10 animals
- Site: The right flank
- Concentrations: 90% w/v in sterile water
- Evaluation (hr after challenge): 6 hours

OTHER:
Challenge controls:
yes as test animals challanged with MI3 90% v/v
Positive control substance(s):
yes
Remarks:
Hexyl cinnamic aldehyde (HCA) as 50% v/v in Alembicol D
Positive control results:
Induction:
Slight to well-defined dermal reactions were observed for all test animals during the induction period and no dermal reactions were observed for the control animals.
Challenge:
The dermal reaction seen in all the ten test animals were more marked than those for controls, therefore the reactions seen in all of the test animals were considered to represent evidence of skin sensitization.
Conclusion:
In this study HCA produced evidence of skin sensitization in all of the ten animals, thus confirming the sensitivity and reliability of experimental technique to detect skin sensitization potential.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
sterile water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of ill health or toxicity were observed
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
sterile water
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No signs of ill health or toxicity were observed
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
MI3, 90% w/v in sterile water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No signs of ill health or toxicity were observed
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
MI3, 90% w/v in sterile water
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No signs of ill health or toxicity were observed
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The Study was conducted to determine the skin sensitization potential of MI3 using the guinea-pig. The study was designed in accordance with OECD guideline method 406 “modified Buehlers test”. The MI3 dose level was chosen to be 90% v/v from a preliminary study, and hexyl cinnamic aldehyde (HCA) was used as positive control. Twenty test and ten control female guinea-pigs received 3 induction applications with either MI3 (90% v/v) or water, respectively, and a challenge test two weeks after the final induction. There was no indicative of systemic toxicity or ill health for any of the guinea-pigs. In this study MI3 did not produce evidence of skin sensitization in any of the twenty test animals.
Executive summary:

The Study was conducted to determine the skin sensitization potential of MI3 using the guinea-pig. The study was designed in accordance with OECD guideline method 406 “modified Buehlers test” the commission directive 96/54/EC, Method B6, and the US EPA Health effects test Guidelines OPPTS 870.2600. The MI3 dose level was chosen to be 90% v/v from a preliminary study and hexyl cinnamic aldehyde (HCA) was used as positive control. Twenty test and ten control female guinea-pigs received 3 induction applications on the shoulder region at Day 1, 8 or 15 with either MI3 (90% v/v) or water, respectively. All animals were challenged test two weeks after the final induction and examined after 24 or 48 hours. There was no indicative of bodyweight loss, systemic toxicity or ill health for any of the guinea-pigs. All animals exposed to HCA showed positive evidence of skin sensitization after 48 hours. In the present study, MI3 did not produce evidence of skin sensitization in any of the twenty test animals.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Remarks:
Buehler method
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2000.09.05 - 2000.10.20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
Buehler test
Justification for non-LLNA method:
n vivo data for MI3 skin sensitization to the guinea-pig was allready avalible prior initiating this registration dossier.
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: X14DesB30, CHD NO. 0180/00-0665 Lot 1, Batch number: X14IS0201014
- Expiration date of the lot/batch: December 2000
- Purity 88%
- Purity test date: 2000.07.13

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: -20 degrees celsius, in the dark.
- Stability under test conditions: NA
- Solubility and stability of the test substance in the solvent/vehicle: NA


TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: defrosted and dosed as supplied
- Final preparation of a solid: dosed as supplied

.

:
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dunkin/Hartley, albino
- Females (if applicable) nulliparous and non-pregnant: [yes]
- Microbiological status of animals, when known: NA
- Age at study initiation: 4 - 7 weeks old.
- Weight at study initiation: 355 - 434 g
- Housing: groups of five animals in suspended metal cages with wire mesh floors
- Diet (e.g. ad libitum): ad libitum, vitamin C enriched guinea pig diet.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: five days
- Indication of any skin lesions: NA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 24 degree celsius
- Humidity (%): 30 - 70 %
- Air changes (per hr): NA
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12hrs light
- IN-LIFE DATES: From: To: 2000.04.09 - 2000.10.20
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 mL of X14DesB30 as supplied (undiluted, purity of 88%) for test animals, and no X14DesB30 for the control group.
Day(s)/duration:
Days 1, 8 and 15. Skin contact for 6 hours per induction exposure.
Adequacy of induction:
highest technically applicable concentration used
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
0.5 mL X14DesB30 as supplied for both test and control animals.
Day(s)/duration:
exposure two weeks after final induction. challange for 6 hours and examination after 24 and 48 hours.
Adequacy of challenge:
other: the maximal practical concentration that could be prepared and dosed topically and not given rise to irritating effects.
No. of animals per dose:
Control animals (n=10).
Test animals (n=20).
Preliminary investigations (n=4).
Details on study design:
RANGE FINDING TESTS:

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: Day 1, Day 8 and Day 15.
- Test groups: X14DesB30 exposure, 20 animals
- Control group: Exposure as test group but test substance omitted, 10 animals
- Site: Left shoulder region
- Frequency of applications: 3 times
- Duration: 6 hours
- Concentrations: 0.5mL X14DesB30 as supplied

B. CHALLENGE EXPOSURE
- No. of exposures: One
- Day(s) of challenge: Two weeks after final induction
- Exposure period: 6 hours
- Test groups: X14DesB30 exposure, 20 animals
- Control group: Exposure as test group, 10 animals
- Site: The right flank
- Concentrations:0.5mL X14DesB30 as supplied
- Evaluation (hr after challenge): 6 hours

OTHER:
Challenge controls:
Yes, as test animals challanged with X14DesB30
Positive control substance(s):
yes
Remarks:
Hexyl cinnamic aldehyde (HCA) as supplied and 50% v/v in Alembicol D
Positive control results:
Induction:
Slight to well-defined dermal reactions were observed for all test animals during the induction period and no dermal reactions were observed for the control animals.
Challenge:
The dermal reaction seen in all the ten test animals were more marked than those for controls, therefore the reactions seen in all of the test animals were considered to represent evidence of skin sensitization.
Conclusion:
In this study HCA produced evidence of skin sensitization in all of the ten animals, thus confirming the sensitivity and reliability of experimental technique to detect skin sensitization potential.
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.5mL X14DesB30 as supplied
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Erythema and Oedema
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.5mL X14DesB30 as supplied
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
Erythema and Oedema
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.5mL X14DesB30 as supplied
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Erythema and Oedema
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.5mL X14DesB30 as supplied
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Erythema and Oedema
Remarks on result:
no indication of skin sensitisation
Interpretation of results:
GHS criteria not met
Conclusions:
The Study was conducted to determine the skin sensitization potential of X14DesB30 using the guinea-pig. The study was designed in accordance with OECD guideline method 406 “modified Buehlers test”. The X14DesB30 dose level was chosen to be as supplied in a preliminary study, and hexyl cinnamic aldehyde (HCA) was used as positive control. Twenty test and ten control female guinea-pigs received 3 induction applications with either X14DesB30 (purity of 88%) or water, respectively, and a challenge test two weeks after the final induction. There was no indicative of systemic toxicity or ill health for any of the guinea-pigs. In this study X14DesB30 did not produce evidence of skin sensitization in any of the twenty test animals.
Executive summary:

The Study was conducted to determine the skin sensitization potential of X14DesB30 using the guinea-pig. The study was designed in accordance with OECD guideline method 406 “modified Buehlers test” the commission directive 96/54/EC, Method B6, and the US EPA Health effects test Guidelines OPPTS 870.2600. The X14DesB30 dose level was chosen to be as supplied in a preliminary study and hexyl cinnamic aldehyde (HCA) was used as positive control. Twenty test and ten control female guinea-pigs received 3 induction applications on the shoulder region at Day 1, 8 or 15 with either X14DesB30 (purity of 88%) or water, respectively. All animals were challenged test two weeks after the final induction and examined after 24 or 48 hours. There was no indicative of bodyweight loss, systemic toxicity or ill health for any of the guinea-pigs. All animals exposed to HCA showed positive evidence of skin sensitization after 48 hours. In the present study, X14DesB30 did not produce evidence of skin sensitization in any of the twenty test animals

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

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on data from OECD 406 guideline studies on two structural analogues, MI3 and X14DesB30 showing no potenteial for skin sensitisation Insulin aspart precusor l is considered without potential for skin sensitisation as wel. Thus, Insulin aspart precusor is not to be classificied as skin sensitiser according to the CLP-criteria.