1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

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

Study period:

1981

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: no guideline study but followed scientifically accepted standards and meet many of the requirements of OECD Test Guideline 474.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)

GLP compliance:

no

Remarks:

not required at time of testing

Type of assay:

micronucleus assay

Test material

Test material information

Constituent 1

Reference substance name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

EC Number:

272-574-2

EC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Cas Number:

68890-66-4

Molecular formula:

C14H23NO2.C2H7NO

IUPAC Name:

1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)pyridin-2(1H)-one, compound with 2-aminoethanol (1:1)

Test animals

Species:

mouse

Strain:

ICL-ICR

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ICR mice
- Age at study initiation: young adult
- Weight at study initiation: no data
- Assigned to test groups randomly: yes
- Fasting period before study: no data
- Housing: plastic cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

intraperitoneal

Vehicle:

- Vehicle(s)/solvent(s) used: Arabian rubber
- Justification for choice of solvent/vehicle: solubility
- Concentration of test material in vehicle: 2% suspension
- Amount of vehicle (if gavage or dermal): n.a.
- Type and concentration of dispersant aid (if powder): n.a.
- Lot/batch no. (if required): no data
- Purity: no data

Details on exposure:

Single and repeated (4 day) administration in 2% Arabian rubber solution intraperitoneally. For the single administration, 125, 62.5 and 31.3 mg/kg body weight (1/2, 1/4, and 1/8 of the LD50) were used. For the 4-day repeated administration, four equal portions of 125, 62.5, 31.3 and 15.6 (1/2, 1/4, 1/8, and 1/16 of the LD50) were given for four days.

Duration of treatment / exposure:

Intraperitoneal injection

Frequency of treatment:

Single and repeated (4 days) treatments

Post exposure period:

24 hours

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
31.3
Basis:
other: 1/8 the LD50 (single application)

Doses / concentrations 2

Remarks:

Doses / Concentrations:
62.5
Basis:
other: 1/4 the LD50 (single application)

Doses / concentrations 3

Remarks:

Doses / Concentrations:
125
Basis:
other: 1/2 the LD50 (single application)

No. of animals per sex per dose:

5 males per group

Control animals:

yes, concurrent vehicle

Positive control(s):

Mitomycin C (2.0 mg/kg body weight)

Examinations

Tissues and cell types examined:

Femoral bone marrow

Details of tissue and slide preparation:

Giemsa smear preparation

Evaluation criteria:

number of micronuclei in polychromatic eryhrocytes

Results and discussion

Test results

Sex:

male

Genotoxicity:

negative

Toxicity:

no effects

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Applicant's summary and conclusion

Conclusions:

Interpretation of results (migrated information): negative
Piroctone olamine is not mutagenic in the micronucleus test

Executive summary:

Piroctone olamine was investigated for the potential to induce chromosomal aberrations in amicronucleus test in ICR male mice. Single and repeated (4 days) administration of Piroctone olamine suspended in 2 % Arabian rubber was given intraperitoneally. The intraperitoneal LD50 in mice was a guide in selecting dose levels. For the single administration, 125, 62.5 and 31.3 mg/kg body weight (approximately 1/2, 1/4 and 1/8 of the LD50, repectively) were used. For the 4 -day repeated administration, four equal portions of 125, 62.5, 31.3 and 15.6 mg/kg body weight (approximately 1/2, 1/4, 1/8 and 1/16 of the LD50) were given daily for four days. 2% Arabian rubber solution was used as the negative control, and the positive control was 2.0 mg/kg body weight mitomycin C. The animals were sacrificed 24 hours after the treatment and the femoral bone marrow was removed for giemsa smear preparation. The incidence of micronucleated cells per 1000 polychromatic erythrocytes per animal was scored. As a result there was no significant increase in the formation of micronuclei in the mouse either in the single or the 4 -day repeated administration, as compared with the negative control. As a result, there was no significant increase in the formation of micronuclei in the mouse polychromatic erythrocytes either in the single or the 4 -day repeated treatment. On the other hand, the group treated with mitomycin C showed a significant increase in micronuclei formation in both, the single as well as the repeated administration. It is concluded that Piroctone olamine has no potential for the induction of chromosome aberrations.