Paracetamol

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian germ cell study: cytogenicity / chromosome aberration

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Evaluation of the ability of paracetamol to produce chromosome aberrations in man

Author:

Ph. Hantson a,, L. de Saint-Georges b p. Mahieu a, E.D. Lonard c, M.C. Crutzen-Fayt c, A. L6onard c

Year:

1996

Bibliographic source:

Mutation Research 368 (1996) 293-300

Materials and methods

Principles of method if other than guideline:

Evaluation of the ability of paracetamol to produce chromosome aberrations in man

GLP compliance:

not specified

Type of assay:

mammalian germ cell cytogenetic assay

Test material

Test material information

Constituent 1

Reference substance name:

Acetaminophen

IUPAC Name:

Acetaminophen

Constituent 2

Reference substance name:

Paracetamol

EC Number:

203-157-5

EC Name:

Paracetamol

Cas Number:

103-90-2

Molecular formula:

C8H9NO2

IUPAC Name:

.

Test material form:

other: Solid

Details on test material:

- Name of test material (as cited in study report): Acetaminophen
- Molecular formula (if other than submission substance): C8-H9-N-O2
- Molecular weight (if other than submission substance): 151.1641
- Substance type: Organic
- Physical state: Solid

Test animals

Species:

other: Human

Details on species / strain selection:

Five male non-smoking healthy volunteers aged 25-35 were chosen among the staff of the Catholic University of Louvain. They had received no medication
nor any exposure to ionising radiation during the last 12 months. Blood was sampled before and 24, 72 and 168 h after ingestion of a single oral dose of 3 g paracetamol. The plasma level of paracetamol was below 2 /zg/ml, 24 h after ingestion.

Sex:

male

Details on test animals or test system and environmental conditions:

- Source:The staff of the Catholic University of Louvain.
- Age at study initiation: volunteers aged 25-35 were chosen

Administration / exposure

Route of administration:

oral: gavage

Details on exposure:

No data

Duration of treatment / exposure:

Single exposure

Frequency of treatment:

Once

Post exposure period:

Yes, 168 hrs

Doses / concentrations

Dose / conc.:

3 other: g

No. of animals per sex per dose:

5

Positive control(s):

No data

Examinations

Tissues and cell types examined:

blood lymphocytes

Details of tissue and slide preparation:

Two cultures were performed from each sample; 0.5 ml blood was added to Ham's F-10 medium and cultured for 48 h. Metaphase slides were prepared, stained in the usual way [6] and coded by an independent technician. From each culture, 250 metaphases (500 per point) were examined blindly for the presence of structural chromatid and chromosome aberrations. Only cells with 44-46 centromeres were taken into consideration. The mitotic index at 48 h was also determined to detect possible effects of treatment on cell proliferation.

Statistics:

ANOVA analysis does not indicate a statistically significant effect of paracetamol on the mitotic index in volunteers .

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

not specified

Vehicle controls validity:

not specified

Negative controls validity:

not specified

Positive controls validity:

not specified

Additional information on results:

No data

Applicant's summary and conclusion

Conclusions:

The ability of paracetamol to induce structural chromosome aberrations in human peripheral blood lymphocytes in vivo was evaluated in volunteers who had been administered a single oral dose of 3 g paracetamol.The patients were observed before treatments and 168hr after treatment.Our observations on volunteers receiving 3 g of paracetamol failed to detect any increase of structural chromosome aberrations in peripheral blood lymphocytes.

Executive summary:

The ability of paracetamol to induce structural chromosome aberrations in human peripheral blood lymphocytes in vivo was evaluated in volunteers who had been administered a single oral dose of 3 g paracetamol.The patients were observed before treatments and 168hr after treatment.Our observations on volunteers receiving 3 g of paracetamol failed to detect any increase of structural chromosome aberrations in peripheral blood lymphocytes. Thus, it is highly unlikely that paracetamol can produce chromosome aberrations in vivo in man and that "there is no unacceptable (if any) mutagenic/carcinogenic risk associated with a sensible use of paracetamol as an analgesic agent".