Phenylephrine hydrochloride

Genetic toxicity: in vivo

Administrative data

Endpoint:

in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus

Remarks:

Type of genotoxicity: chromosome aberration

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP, non guideline study published in the NTP database with limitations in design and/or reporting but otherwise adequate for assessment.

Data source

Reference

Reference Type:

grey literature

Title:

Unnamed

Year:

1993

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Male F344 rats were exposed to the test substance intraperitoneal for 3 consecutive days (0, 4, 8, 17, 35 mg/kg). The bone marrow was harvested 24 hours after the last injection and 2000 polychromatic erythrocytes (PCEs, reticulocytes; immature erythrocytes) are scored per animal for frequency of micronucleated cells.

GLP compliance:

not specified

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

Phenylephrine hydrochloride

EC Number:

200-517-3

EC Name:

Phenylephrine hydrochloride

Cas Number:

61-76-7

Molecular formula:

C9H13NO2.ClH

IUPAC Name:

phenylephrine hydrochloride

Details on test material:

-Chemical name: Phenylephrine Hydrochloride

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

Phosphate Buffered Saline (PBS)

Duration of treatment / exposure:

Animals were exposed daily for 3 days.

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
4, 8, 17, 35 mg/kg
Basis:
nominal conc.

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Positive control(s):

5 rats were treated with 7.5 mg/kg Cyclophosphamide (CPA)

Examinations

Tissues and cell types examined:

polychromatic erythrocytes

Details of tissue and slide preparation:

Harvesting of the bone marrow usually occurs 24 hours after the last dosing. The animals are euthanized by CO2 inhalation and the femurs are removed. The bone marrow is flushed from the femurs and spread onto slides. The slides are air-dried, fixed, and stained with a fluorescent DNA-specific stain that easily illuminates any micronuclei that may be present. Typically, 2000 polychromatic erythrocytes (PCEs, reticulocytes; immature erythrocytes) are scored per animal for frequency of micronucleated cells in each of 5 animals per dose group. In addition, the percentage of PCEs among the total erythrocyte population in the bone marrow is scored for each dose group as an indicator of chemical-induced toxicity. In non-treated healthy mice and rats, the %PCE in bone marrow is usually around 50-60%. If a chemical interferes with the production of erythrocytes in the bone marrow, then the %PCE in the bone marrow may decline from the typical normal level. Conversely, if erythrocyte production is stimulated by chemical exposure, then a higher percentage of immature erythrocytes may be observed.

Statistics:

A formal statistical analysis of the data is performed that includes a trend test, to determine if there is an overall increase across all doses in the frequency of cells containing micronuclei, and a pairwise comparison of each dose group to the corresponding control, to see if any one dose group is statistically different from the control group in frequency of micronucleated cells. Data are typically presented as the mean number of micronucleated cells per 1,000 cells for each treatment group. A positive trend test is one in which the P value is equal to or less than 0.025. For the slide-based micronucleus data, the micronucleus frequency in any dose group is considered significantly elevated over the control group if the P value is equal to or less than 0.025 divided by the number of chemical-treatment groups. Thus, if the number of treated groups is 3, then the required pairwise P value is 0.008. This adjustment in the pairwise P value is a correction for multiple comparisons of the same data.

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

yes

Remarks:

at 17 and 35 mg/kg all rats died.

Vehicle controls validity:

valid

Negative controls validity:

not applicable

Positive controls validity:

valid