Paracetamol

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:

weight of evidence

Reliability:

2 (reliable with restrictions)

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

Duplicate skin prick test

GLP compliance:

not specified

Type of study:

other: Duplicate skin prick test

Species:

human

Sex:

female

Route:

epicutaneous, open

Vehicle:

other: saline 0.9%

Concentration / amount:

100 mg/mL

Route:

epicutaneous, open

Vehicle:

other: saline 0.9%

Concentration / amount:

100 mg/mL

No. of animals per dose:

four patients (All were women, aged 21 to 65 (mean age 41))

Details on study design:

Duplicate skin prick tests were per- formed by the same physician on the volar aspect of the forearm, Skin tests were performed with a solution of acetaminophen (Apiretal gotas) diluted in saline 0.9% at a concentration of 100 mg/mL. Histamine phosphate (10 mg/mL) and saline (0.9% commercial source) were used as positive and neg-ative controls, respectively.

Positive control substance(s):

yes

Remarks:

Histamine phosphate

Reading:

1st reading

Hours after challenge:

1

Group:

test chemical

Dose level:

250 mg and 500 mg,( Patient 1 received 75 mg of acetaminophen and the other three received 650 mg in a single dose. (Because a different physician performed the challenge on patient 1, this patient received a lower dosage.)

No. with + reactions:

2

Total no. in group:

4

Clinical observations:

Not sensitizing

Remarks on result:

other: see Remark

Remarks:

Reading: 1st reading. . Hours after challenge: 1.0. Group: test group. Dose level: 250 mg and 500 mg,( Patient 1 received 75 mg of acetaminophen and the other three received 650 mg in a single dose. (Because a different physician performed the challenge on patient 1, this patient received a lower dosage.). No with. + reactions: 2.0. Total no. in groups: 4.0. Clinical observations: Not sensitizing.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Acetaminophen could be a potential irritant at 100 mg/mL but one of the control group also showed a wheal or erythema response and since the skin prick tests were negative in two of four patients but although this is common in drug hypersensitivity.It can be concluded to be negative in terms of sensitization.

Executive summary:

Study was conducted on 4 patients and 30 individuals to check the hypersensitivity reaction as well as a skin prick test results induced by acetaminophen after an induction and challenge exposure. Skin tests were performed with a solution of acetaminophen (Apiretal gotas) diluted in saline 0.9% at a concentration of 100 mg/mL. Histamine phosphate (10 mg/mL) and saline (0.9% commercial source) were used as positive and negative controls, respectively.Single-blind oral challenges were performed with aspirin, 250 mg and 500 mg, in a cumulative fashion at 1-hour intervals. All patients tolerated the challenge without adverse effects. Oral challenges with acetaminophen were performed on different day.

The study itself stated that elevated specific IgE antibodies to acetaminophen were observed .

But the reactions to acetaminophen reported worldwide cannot be considered significant, therefore acetaminophen is a safe drug.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

Migrated from Short description of key information:

Paracetamol was  not found to be sensitising to humans

Justification for selection of skin sensitisation endpoint:

Acetaminophen could be a potential irritant at 100 mg/mL but one of the control group  also showed a wheal or erythema response and   since the skin prick tests were negative in two of four patients but although this is common in drug hypersensitivity.It can be concluded to be negative in terms of sensitization.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information:

Various data sources, having Klimisch rating 2 have been used to arrive at the conclusion relating to the skin sensitization Based on the QSAR prediction model version 3.1 paracetamol was predicted to be non sensitizing on guinea pig maximization test.Berta Juliade Paramo et.alalso reported (Annals of Allergy, Asthma & Immunology Volume 85, Issue 6, December 2000, Pages 508–511) paracetamol to be non sensitizing at concen. Of 100mg/ml. after skin prick test.

Justification for classification or non-classification

The test substance Paracetamol is considered as sensitising for the purpose of classification.