Reaction mass of Amines, hydrogenated tallow alkyl and azelaic acid and lithium hydroxide

Endpoint summary

Description of key information

No adverse effects were observed in the studies with two read across substances, dilithium azelate and reaction mixture of hydrogenated tallow alkyl amines with sebacic acid and lithium hydroxide and both substances were considered to be not sensitising.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Reference 1

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is carried out in accordance to OECD guideline 429, EU method B.42 and is GLP compliant. Therefore, it is given reliability rating of 1 (reliable without restrictions).

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included under 'Attached justification' in IUCLID section 13 and 'Cross-reference'.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

other: Local Lymph Node Assay

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Makrolon cages containing sterilised sawdust
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

2, 15 and 30 % test item w/w

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS: 15 and 30 % test item w/w using 2 animals per concentration

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 days
- Test groups: 5 animals exposed to each concentration
- Control group: 5 animals exposed to the vehicle
- Site: dorsal surface of both ears
- Frequency of applications: Days 1, 2, 3
- Duration: 6 days
- Concentrations: 2, 15 and 30 % test item w/w

SCORE:
Erythema and eschar formation:
No erythema ..............................................................................……………….....................……………………….. 0
Very slight erythema (barely perceptible) ..............................................................……………………………… 1
Well-defined erythema ...................................................................……………………....................……………… 2
Moderate to severe erythema (beet redness) to slight eschar formation (injuries in depth) .........……… 3
Severe erythema (beet redness) to eschar formation preventing grading of erythema .................……… 4

Positive control substance(s):

not specified

Key result

Parameter:

other: Migrated information from in vivo LLNA study

Remarks on result:

other: All readings. Group: test group. Dose level: 2, 15% and 30%. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.

Parameter:

SI

Value:

1

Test group / Remarks:

dose level: 2 % test item w/w

Parameter:

SI

Value:

0.9

Test group / Remarks:

dose level: 15 % test item w/w

Parameter:

SI

Value:

0.6

Test group / Remarks:

dose level: 30 % test item w/w

No irritation and no signs of systemic toxicity were observed in any of the animals.

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size.

No macroscopic abnormalities of the surrounding area were noted for any of the animals.

Mean DPM/animal values for the experimental groups treated with test item concentrations 2, 15 and 30% were 899, 780 and 584 DPM, respectively. The mean DPM/animal value for the vehicle control group was 911 DPM. The SI values calculated for the item concentrations 2, 15 and 30% were 1.0, 0.9 and 0.6, respectively.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Dilithium adipate would not be regarded as a skin sensitizer.

Executive summary:

This study is carried out in accordance to OECD guideline 429, EU method B.42 and is GLP compliant. Therefore, it is given reliability rating of 1 (reliable without restrictions). Dilithium adipate would not be regarded as a skin sensitizer.

Reference 2

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2015

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is carried out in accordance to OECD guideline 429, EU method B.42 and is GLP compliant. Therefore, it is given reliability rating of 1 (reliable without restrictions).

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included under 'Attached justification' in IUCLID section 13 and 'Cross-reference'.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

GLP compliance:

yes (incl. QA statement)

Type of study:

other: Local Lymph Node Assay

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: Approximately 10 weeks old
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean.
- Housing: Makrolon cages containing sterilised sawdust
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%): 40-70
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

acetone/olive oil (4:1 v/v)

Concentration:

2, 15 and 30 % test item w/w

No. of animals per dose:

5

Details on study design:

RANGE FINDING TESTS: 15 and 30 % test item w/w using 2 animals per concentration

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 3
- Exposure period: 6 days
- Test groups: 5 animals exposed to each concentration
- Control group: 5 animals exposed to the vehicle
- Site: dorsal surface of both ears
- Frequency of applications: Days 1, 2, 3
- Duration: 6 days
- Concentrations: 2, 15 and 30 % test item w/w

SCORE:
Erythema and eschar formation:
No erythema ..............................................................................……………….....................……………………….. 0
Very slight erythema (barely perceptible) ..............................................................……………………………… 1
Well-defined erythema ...................................................................……………………....................……………… 2
Moderate to severe erythema (beet redness) to slight eschar formation (injuries in depth) .........……… 3
Severe erythema (beet redness) to eschar formation preventing grading of erythema .................……… 4

Positive control substance(s):

not specified

Parameter:

other: Migrated information from in vivo LLNA study

Remarks on result:

other: Reading: other: All readings. Group: test group. Dose level: 2, 15% and 30%. No with. + reactions: 0.0. Total no. in groups: 15.0. Clinical observations: None.

Parameter:

SI

Value:

1

Test group / Remarks:

dose level: 2 % test item w/w

Parameter:

SI

Value:

0.9

Test group / Remarks:

dose level: 15 % test item w/w

Parameter:

SI

Value:

0.6

Test group / Remarks:

dose level: 30 % test item w/w

No irritation and no signs of systemic toxicity were observed in any of the animals.

No mortality occurred and no clinical signs of systemic toxicity were observed in the animals of the main study. Body weights and body weight gain of experimental animals remained in the same range as controls over the study period.

All auricular lymph nodes of the animals of the experimental and control groups were considered normal in size.

No macroscopic abnormalities of the surrounding area were noted for any of the animals.

Mean DPM/animal values for the experimental groups treated with test item concentrations 2, 15 and 30% were 899, 780 and 584 DPM, respectively. The mean DPM/animal value for the vehicle control group was 911 DPM. The SI values calculated for the item concentrations 2, 15 and 30% were 1.0, 0.9 and 0.6, respectively.

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

Dilithium adipate would not be regarded as a skin sensitizer.

Executive summary:

This study is carried out in accordance to OECD guideline 429, EU method B.42 and is GLP compliant. Therefore, it is given reliability rating of 1 (reliable without restrictions). Dilithium adipate would not be regarded as a skin sensitizer.

Reference 3

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included under 'Attached justification' in IUCLID section 13 and 'Cross-reference'.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

according to guideline

Guideline:

other: 96/54 EC, B.6 (Guinea-Pig Maximisation Test (GMPT)) OECD 406

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An in vivo study according to OCED 406 was conducted in 1999, before the first version of the LLNA (OECD 429) was issued in 2002.

Species:

guinea pig

Strain:

other: Hsd Poc:DH

No. of animals per dose:

Number of animals in test group: 10
Number of animals in negative control group: 5

Details on study design:

Concentration of test material and vehicle used at induction:
a) Intradermal injection: Day 0
Test group: 0.1 ml test solution
(2000 mg in 8 ml NaCl 0.9 %) = 25 % test substance
Control group: 0.1 ml NaCl 0.9 %
b) Topical application: Day 6
Test- and control group: 0.5 ml 10 % Natriumlaurylsulfat
in vaseline
Day 7:
Test group: 2 g test substance (100 %), moistened with
CMC 1 %
Control group: CMC 1 %
Concentration of test material and vehicle used for each challenge:
Topical application: Day 20
Test- and control group: A patch loaded with 2 g test substance moistened with CMC 1 % was applied to the left flank of the animals and a patch loaded with the vehicle to the right flank (intraspecific control), respectively.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

Maximum concentration not causing irritating effects in preliminary test: 100 %

Signs of irritation during induction:

No signs of irritation were recorded, there were no effects observed. For the first stage of induction the highest concentration applicable as intradermal injection (2 g/8 ml) was chosen.

Evidence of sensitisation of each challenge concentration: none

Other observations: none

Interpretation of results:

GHS criteria not met

Reference 4

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Justification for type of information:

REPORTING FORMAT FOR THE ANALOGUE APPROACH
Further information is included under 'Attached justification' in IUCLID section 13 and 'Cross-reference'.

Reason / purpose for cross-reference:

read-across source

Qualifier:

according to guideline

Guideline:

other: 96/54 EC, B.6 (Guinea-Pig Maximisation Test (GMPT)) OECD 406

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

An in vivo study according to OCED 406 was conducted in 1999, before the first version of the LLNA (OECD 429) was issued in 2002.

Species:

guinea pig

Strain:

other: Hsd Poc:DH

No. of animals per dose:

Number of animals in test group: 10
Number of animals in negative control group: 5

Details on study design:

Concentration of test material and vehicle used at induction:
a) Intradermal injection: Day 0
Test group: 0.1 ml test solution
(2000 mg in 8 ml NaCl 0.9 %) = 25 % test substance
Control group: 0.1 ml NaCl 0.9 %
b) Topical application: Day 6
Test- and control group: 0.5 ml 10 % Natriumlaurylsulfat
in vaseline
Day 7:
Test group: 2 g test substance (100 %), moistened with
CMC 1 %
Control group: CMC 1 %
Concentration of test material and vehicle used for each challenge:
Topical application: Day 20
Test- and control group: A patch loaded with 2 g test substance moistened with CMC 1 % was applied to the left flank of the animals and a patch loaded with the vehicle to the right flank (intraspecific control), respectively.

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

10

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

100 %

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

Not reported

Remarks on result:

no indication of skin sensitisation

Group:

positive control

Remarks on result:

not measured/tested

Maximum concentration not causing irritating effects in preliminary test: 100 %

Signs of irritation during induction:

No signs of irritation were recorded, there were no effects observed. For the first stage of induction the highest concentration applicable as intradermal injection (2 g/8 ml) was chosen.

Evidence of sensitisation of each challenge concentration: none

Other observations: none

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

 

No skin sensitisation data for the substance reaction mass of amines, hydrogenated tallow alkyl and azelaic acid and lithium hydroxide is available.

However, a skin sensitisation study using guinea pigs was conducted according to OECE 406 method on reaction mixture of hydrogenated tallow alkyl amines with sebacic acid and lithium hydroxide (BIOSERVICE SCIENTIFIC LABORATORIES, 1999). No positive responses were observed after the challenge exposure, which was further confirmed by a reduced local lymph node assay (rLLNA) of the single (high) dose group (≥10%) and a concurrent negative control group. No evidence of sensitisation or irritation were detected and the substance was not considered classifiable.

This endpoint for dilithium azelate has been filled based on read across to a substance in the same category (dilithium adipate). Dilithium adipate (C6) was subjected to a Local Lymph Node Assay (LLNA) in mice according to OECD Guideline 429 (Latour 2015). This substance was chosen as it represented the potential worst case substance from the category ‘dilithium salts of linear (unbranched) dicarboxylic acids with hydrocarbon chain lengths of 6, 9 and 10’ since it had the highest relative lithium content and the lowest carbon chain length. Dilithium adipate was a non-sensitiser under the conditions of the test, with the highest Stimulation Index of 1.0 at 2% concentration in acetone/olive oil, with the EC3 value being >30% (the highest concentration tested).

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Negative results were produced in the studies with two read across substances, dilithium azelate and reaction mixture of hydrogenated tallow alkyl amines with sebacic acid and lithium hydroxide.

Therefore, no classification is considered relevant for this endpoint for substance reaction mass of amines, hydrogenated tallow alkyl and azelaic acid and lithium hydroxide.