Absolute of Nicotiana tabacum (Solanaceae) obtained from leaves by organic solvent treatment and subsequent ethanol extraction

Endpoint summary

Description of key information

Human Repeated Insult Patch Test (K, Rel2): not a skin sensitizer at 1%.

In addition, based on existing data on constituents (additivity principles), the registered substance has no known constituents considered as skin sensitisers.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Remarks:

Human Repeat Insult Patch Test

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1976

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Human Repeat Insult Patch Test using generally-accepted methods.

Qualifier:

no guideline followed

Principles of method if other than guideline:

Repeated Insult Patch Test was performed to confirm that repeated applications of the product under maximized conditions, in healthy subjetcs, does not induce delayed contact allergy reactions. A secondary objective is to determine the irritating potential of the product first after a single application and second after repeated applications.

GLP compliance:

no

Remarks:

study has been conducted in the spirit of the good Clinical Practice

Type of study:

patch test

Justification for non-LLNA method:

HRIPT study in human volunteers already available

Species:

other: Human

Details on test animals and environmental conditions:

- Number of subjects empanelled: 36 healthy inmate volunteers
- Number of subjects completed the study: 29 healthy inmate volunteers (4 dropped out, 2 transferred and one with SLS positive)
- Age: human 18+ yrs.

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

1% test item in petrolatum

Route:

epicutaneous, occlusive

Vehicle:

petrolatum

Concentration / amount:

1% test item in petrolatum

Details on study design:

Maximization tests (Modified after JID 47393-409, 1966):
Test materials (1%) were applied under occlusion to the same site on the volar forearms of all subjects for 5 alternate day 48 hour periods. Patch sites were pre-tested for 24 hours with 5% aqueous sodium lauryl sulfate (SLS) under occlusion for the initial patch only.
Following a 10-14 day rest period, challenge patches of all materials were applied under occlusion to fresh sites for 48 hours. Challenge applications were preceded by 30 minute applications of 5% aqueous SLS under occlusion on the left side of the back whereas the test materials were applied without SLS treatment on the right side.
Additional SLS controls were placed on the left and petrolatum on the right and labeled site 5. Questionable reactions were followed on a daily basis for 1 week and retests were applied later at new sites.

Challenge controls:

SLS controls were placed on the left and petrolatum on the right and labeled site 5.

Positive control substance(s):

no

Positive control results:

Not applicable

Reading:

1st reading

Hours after challenge:

48

Group:

positive control

Dose level:

Not applicable

No. with + reactions:

0

Total no. in group:

0

Remarks on result:

not measured/tested

Reading:

2nd reading

Hours after challenge:

72

Group:

positive control

Dose level:

Not applicable

No. with + reactions:

0

Total no. in group:

0

Remarks on result:

not measured/tested

Reading:

2nd reading

Hours after challenge:

72

Group:

negative control

Dose level:

Petrolatum

No. with + reactions:

0

Total no. in group:

29

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

negative control

Dose level:

Petrolatum

No. with + reactions:

0

Total no. in group:

29

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

72

Group:

test chemical

Dose level:

1% test material presumably in petrolatum

No. with + reactions:

0

Total no. in group:

29

Remarks on result:

no indication of skin sensitisation

Key result

Reading:

1st reading

Hours after challenge:

48

Group:

test chemical

Dose level:

1% test material presumably in petrolatum

No. with + reactions:

0

Total no. in group:

29

Remarks on result:

no indication of skin sensitisation

No evidence of irritation or sensitization were observed however with the other three materials applied. Therefore, the test item produced no reactions that were considered allergic or irritant in the twenty-nine subjects tested.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the test conditions, the test material can be considered as non-sensitizing at 1%.

Executive summary:

In a Human Repeated Insult Patch Test, the primary irritation and sensitization properties of the test sample was tested on 29 volunteers. The test material (1%) was applied under occlusion to the same site on the volar forearms of all subjects for 5 alternate day 48 hour periods. Patch sites were pre-tested for 24 hours with 5% aqueous sodium lauryl sulfate (SLS) under occlusion for the initial patch only. Following a 10-14 day rest period, challenge patches of all materials were applied under occlusion to fresh sites for 48 hours. Challenge applications were preceded by 30 minute applications of 5% aqueous SLS under occlusion on the left side of the back whereas the test materials were applied without SLS treatment on the right side. Additional SLS controls were placed on the left and petrolatum on the right and labeled site 5. Questionable reactions were followed on a daily basis for 1 week and retests were applied later at new sites.

No evidence of skin irritation or sensitisation was observed in the 29 subjects tested.

 

Under the test conditions, the test material can be considered as non-sensitizing at 1%.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

HRIPT test

One study was available and considered as key study (Epstein, 1976). In a Human Repeated Insult Patch Test, the primary irritation and sensitization properties of the test sample was tested on 29 volunteers. The test material (1%) was applied under occlusion to the same site on the volar forearms of all subjects for 5 alternate day 48 hour periods. Patch sites were pre-tested for 24 hours with 5% aqueous sodium lauryl sulfate (SLS) under occlusion for the initial patch only. Following a 10-14 day rest period, challenge patches of all materials were applied under occlusion to fresh sites for 48 hours. Challenge applications were preceded by 30 minute applications of 5% aqueous SLS under occlusion on the left side of the back whereas the test materials were applied without SLS treatment on the right side. Additional SLS controls were placed on the left and petrolatum on the right and labeled site 5. Questionable reactions were followed on a daily basis for 1 week and retests were applied later at new sites.

No evidence of skin irritation or sensitisation was observed in the 29 subjects tested.

 

The test material can be considered as non-sensitizing at 1%.

 

Data on constituents

The compound is composed of several identified constituents and in that, it can be considered as a mixture according to the definition of the CLP Regulation.

Based on existing data on constituents (additivity principles), the registered substance has no known constituents considered as Skin sensitisers. These data complement the previous study.

 

Constituent	CAS	Classification according to the Regulation (EC) No. 1272/2008 (CLP)	Source
Nicotine	54-11-5	Not a skin sensitiser	ECHA disseminated dossier
Alpha linolenic acid	463-40-1	Not a skin sensitiser	CLP notifications from major numbers of notifiers
Palmitic acid	57-10-3	Not a skin sensitiser	ECHA disseminated dossier
Linoleic acid	60-33-3	Not a skin sensitiser	CLP notifications
Oleic acid	112-80-1	Not a skin sensitiser	CLP notifications
Myristic acid	544-63-8	Not a skin sensitiser	CLP notifications
Stearic acid	57-11-4	Not a skin sensitiser	ECHA disseminated dossier
Icosanoic acid	506-30-9	Not a skin sensitiser	ECHA disseminated dossier
Nervonic acid	506-37-6	Not a skin sensitiser	CLP notifications
Vaccenic acid	693-72-1	Not a skin sensitiser	CLP notifications
Ethyl alcohol	64-17-5	Not a skin sensitiser	ECHA disseminated dossier

 

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

 

Harmonized classification:

The substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

 

Self classification:

Based on the available study and data on constituents, no additional self-classification is proposed according to the CLP and to the GHS.

 

No data was available for respiratory sensitisation. However, this substance is not a skin sensitizer, therefore according to Figure R.7.3 -2 of the Chapter R.7 (V 4.1 - October 2015) the chemical is not considered as a respiratory sensitizer.