Hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation

Remarks:

in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from peer reviewed journal

Qualifier:

according to guideline

Guideline:

other: Data is from Journal with permission

Principles of method if other than guideline:

The allergic potential of patent blue V in 7,917 patients who participated in the NEW START training Programme and the ALMANAC trial was determined in the skin sensitization experiment conducted.

GLP compliance:

not specified

Type of study:

not specified

Species:

human

Strain:

not specified

Sex:

female

Details on test animals and environmental conditions:

no data

Route:

other: ALMANAC study: Close to the tumour NEW START training programme: Subdermally at the areola skin margin of the index quadrant

Vehicle:

other: Normal saline

Concentration / amount:

ALMANAC study: 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml NEW START training programme: undiluted 2 ml of 2.5% patent blue V dye or 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml

Concentration / amount:

ALMANAC study: 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml NEW START training programme: undiluted 2 ml of 2.5% patent blue V dye or 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml

No. of animals per dose:

7917 patients

Details on study design:

Details on study designRANGE FINDING TESTS:MAIN STUDYA. INDUCTION EXPOSURE :ALMANAC TREATMENT- No. of exposures: 1- Exposure period: No data available- Test groups: 7917- Control group: No data available- Site: - Frequency of applications: Around the tumour- Duration: No data available- Concentrations: 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml with normal salineNEW START training programme: - No. of exposures: 1- Exposure period: No data available- Test groups: 7917- Control group: No data available- Site: - Frequency of applications: subdermally at the areolaskin margin of the index quadrant.- Duration: No data available- Concentrations: 2 ml of 2.5% patent blue V dye or 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml with normal salineB. CHALLENGE EXPOSURE- No. of exposures: No data available- Day(s) of challenge: No data available- Exposure period: No data available- Test groups: No data available- Control group: No data available- Site: No data available- Concentrations: No data available- Evaluation (hr after challenge): No data availableOTHER: No data available

Challenge controls:

No data available

Positive control substance(s):

not specified

Group:

test chemical

Dose level:

ALMANAC study: 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml NEW START training programme: undiluted 2 ml of 2.5% patent blue V dye or 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml

No. with + reactions:

72

Total no. in group:

7 917

Clinical observations:

Total allergicDnon-allergic reactions72

Remarks on result:

other: see Remark

Remarks:

Group: test group. Dose level: ALMANAC study: 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml NEW START training programme: undiluted 2 ml of 2.5% patent blue V dye or 2 ml of 2.5% aqueous solution of patent blue V diluted to 5 ml . No with. + reactions: 72.0. Total no. in groups: 7917.0. Clinical observations: Total allergicDnon-allergic reactions72.

Clinical observations:

Allergic reactions
Grade I	Urticaria, blue hives, pruritis, or generalised rash	23 patients
Grade II	Transient hypotension/bronchospasm/ laryngospasm	16 patients
Grade III	Severe hypotension (requiring vasopressor support) and/or change/abandoning of planned procedure and/or HDU/ITU admission	5 patients
Grade IV	Cardio-respiratory arrest and/or death	-
Unspecified		24 patients
Non-allergic reactions
Skin tattooing		1 patients
Bluish hue persisting for few hours		3 patients
Total allergicDnon-allergic reactions		72

Interpretation of results:

sensitising

Conclusions:

The favourable allergic potential of patent blue V suggests the test material to be sensitizing to the skin of patients.

Executive summary:

The adverse reactions of patent blue V in 7,917 patients who participated in the NEW START training programme and the ALMANAC trial was studied. All patients underwent sentinel lymph node biopsy for breast carcinoma using patent blue V.

In the ALMANAC study, the test compound was injected around the tumour. In the NEW START training programme, the test compound was injectedsubdermally at the areola skin margin of the index quadrant.

In total, 72 of 7,917 (0.9%) patients experienced adverse reactions : non-allergic reactions were observed in 4 (0.05%) patients, 23 (0.3%) patients had minor grade I allergic skin reactions (urticaria, blue hives, pruritis, or generalised rash) and 16 (0.2%) had grade II reactions (transient hypotension/ bronchospasm/ laryngospasm). Severe Grade III reactions (severe hypotension requiring vasopressor support and/or change/abandoning of planned procedure and/or HDU/ITU admission) were noted in 5 (0.06%) patients. The type of adverse reaction was not specified in 24 (0.3%) patients. No mortality was recorded.

The favourable allergic potential of patent blue V suggests the test material to be sensitizing to the skin of patients.

According to the publication, the test material is positive to induce skin sensitization.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization

In the study performed by L. Barthelmes , A. Goyal , R.G. Newcombe , F. McNeill c, R.E. Mansel on behalf of the NEW START and ALMANAC study groups 2010, the skin sensitization effects were observed for CAS 129-17-9 (patent blue V) in humans. The adverse reactions of patent blue V in 7,917 patients who participated in the NEW START training programme and the ALMANAC trial was studied. All patients underwent sentinel lymph node biopsy for breast carcinoma using patent blue V. In the ALMANAC study, the test compound was injected around the tumour. In the NEW START training programme, the test compound was injected subdermally at the areola skin margin of the index quadrant. In total, 72 of 7,917 (0.9%) patients experienced adverse reactions : non-allergic reactions were observed in 4 (0.05%) patients, 23 (0.3%) patients had minor grade I allergic skin reactions (urticaria, blue hives, pruritis, or generalised rash) and 16 (0.2%) had grade II reactions (transient hypotension/ bronchospasm/ laryngospasm). Severe Grade III reactions (severe hypotension requiring vasopressor support and/or change/abandoning of planned procedure and/or HDU/ITU admission) were noted in 5 (0.06%) patients. The type of adverse reaction was not specified in 24 (0.3%) patients. No mortality was recorded. The favourable allergic potential of patent blue V suggests the test material to be sensitizing to the skin of patients.

 

 

Another study reported by C. J. Barber 1989 for the target CAS 129-17-9 (patent blue V), the adverse effects of test chemical on skin was observed in humans patients. The patient, a 39-year-old woman, was being investigated for presumed lymph oedema of the right lower limb. One millilitre of patent blue violet was injected subcutaneously into the web spaces of the right foot. Five minutes following this, she complained of intense itching in the medial right calf. Examination revealed quite marked dermal staining with the blue dye and the stained skin was raised and pale. Inspection of the foot showed the skin to be raised into a wheal which exactly demarcated the site of the dye and tracked along the line of two lymphatics on the dorsum of the foot. The patient rapidly developed a sensation of swelling and constriction in the throat and difficulty in breathing. Auscultation revealed no evidence of bronchospasm. Endotracheal intubation was not required; the throat swelling subsided within the next hour. Within that period the patient developed a generalized rash affecting all four limbs and the face. This consisted of raised, irregular, pale patches with red margins. There was confluent blue staining of the skin of the right leg which was again marginated by a raised red line. The day following the reaction, the generalized rash was much less marked but the skin of the right lower limb below the knee remained uniformly blue/grey in colour with a clearly defined edge proximally. The patient showed sensitization reaction upon subcutaneous injection with the test chemical Patent Blue Violet.

 

Based upon the study by Kirsti Kalimo and Heikki Saarni 1981, skin sensitization effects of CAS 129-17-9 (patent blue V) was observed in humans. Case report 1: A 31 yr old man with Hodgkin’s lymphoma was scheduled for lymphangiography. A few minutes after PB injection, the patient noticed marked erythema and swelling of the feet starting from the site of PB injection. He was further tested with 2.5% Patent Blue and was found to react positively. Case report 2: A 61 yr old female cleaner who suffered from hand dermatitis had received skin prick test with PB, developing a wheal. Case report 3: one patient remembered itching and skin erythema previously with the use of blue colored washing powder. This patient developed cardiovascular collapse after a PB injection prior to lymphography. Case report 4: the patient experienced asthma like symptoms when in contact with blue colored carpet. The patient showed positive skin prick test reaction to PB. In all the cases, the test material Patent Blue shows positive skin sensitization reaction.

On the basis of available information for the target, the test substanceCAS 129-17-9 (patent blue V) can be considered as sensitising to the skin.

Migrated from Short description of key information:

In the study performed by L. Barthelmes , A. Goyal , R.G. Newcombe , F. McNeill c, R.E. Mansel  on behalf of the NEW START and ALMANAC study groups 2010, the skin sensitization effects were observed for CAS 129-17-9 (patent blue V) in humans. The adverse reactions of patent blue V in 7,917 patients who participated in the NEW START training programme and the ALMANAC trial was studied. All patients underwent sentinel lymph node biopsy for breast carcinoma using patent blue V. In the ALMANAC study, the test compound was injected around the tumour. In the NEW START training programme, the test compound was injected subdermally at the areola skin margin of the index quadrant. In total, 72 of 7,917 (0.9%) patients experienced adverse reactions : non-allergic reactions were observed in 4 (0.05%) patients, 23 (0.3%) patients had minor grade I allergic skin reactions (urticaria, blue hives, pruritis, or generalised rash) and 16 (0.2%) had grade II reactions (transient hypotension/ bronchospasm/ laryngospasm). Severe Grade III reactions (severe hypotension requiring vasopressor support and/or change/abandoning of planned procedure and/or HDU/ITU admission) were noted in 5 (0.06%) patients. The type of adverse reaction was not specified in 24 (0.3%) patients. No mortality was recorded. The favourable allergic potential of patent blue V suggests the test material to be sensitizing to the skin of patients.

Justification for selection of skin sensitisation endpoint:

In the study performed by L. Barthelmes , A. Goyal , R.G. Newcombe , F. McNeill c, R.E. Mansel  on behalf of the NEW START and ALMANAC study groups 2010, the skin sensitization effects were observed for CAS 129-17-9 (patent blue V) in humans. The adverse reactions of patent blue V in 7,917 patients who participated in the NEW START training programme and the ALMANAC trial was studied. All patients underwent sentinel lymph node biopsy for breast carcinoma using patent blue V. In the ALMANAC study, the test compound was injected around the tumour. In the NEW START training programme, the test compound was injected subdermally at the areola skin margin of the index quadrant. In total, 72 of 7,917 (0.9%) patients experienced adverse reactions : non-allergic reactions were observed in 4 (0.05%) patients, 23 (0.3%) patients had minor grade I allergic skin reactions (urticaria, blue hives, pruritis, or generalised rash) and 16 (0.2%) had grade II reactions (transient hypotension/ bronchospasm/ laryngospasm). Severe Grade III reactions (severe hypotension requiring vasopressor support and/or change/abandoning of planned procedure and/or HDU/ITU admission) were noted in 5 (0.06%) patients. The type of adverse reaction was not specified in 24 (0.3%) patients. No mortality was recorded. The favourable allergic potential of patent blue V suggests the test material to be sensitizing to the skin of patients.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The chemical CAS 129-17-9 hydrogen [4-[4-(diethylamino)-2',4'-disulphonatobenzhydrylidene]cyclohexa-2,5-dien-1-ylidene]diethylammonium, sodium salt is likely to be "sensitizing" to the skin of human as per the available experimental data. Thus, the chemical is classified as being "sensitizing"