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Toxicological information

Genetic toxicity: in vivo

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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)
Rationale for reliability incl. deficiencies:
other: Near-guideline study, pre-GLP, well described methods and detailed results, generally acceptable overall.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1974
Report Date:
1974

Materials and methods

Principles of method if other than guideline:
Groups of 5 male rats were administered by gastric intubation either a single dose of propylene glycol at dose levels of 30, 2500 and 5000 mg/kg bw (acute study), or 5 doses 24 hours apart (subacute study). In the acute study animals were killed 6, 24 and 48 hours post-administration, in the subacute study 6 hours after the last dose. The bone marrow slides were prepared and diploid cells were scored for chromatid gaps and breaks, chromosome gaps and breaks, reunions, cells with greater than 10 aberrations, polyploidy, pulverization and any other chromosomal aberrations which were observed.
GLP compliance:
no
Type of assay:
chromosome aberration assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): propylene glycol, FDA 71-56
- Lot/batch No.: #YA07102A
- Supplier: The Food and Drug Administration

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Flow Laboratories random-bred, closed colony
- Age at study initiation: 10-12 weeks
- Weight at study initiation: 280-350 g
- Assigned to test groups randomly: [no/yes, under following basis: ]
- Housing: 1-5 per cage
- Diet (e.g. ad libitum): commercial 4% fat diet.
- Acclimation period: 4-11 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
Saline
Duration of treatment / exposure:
Either a single dose or 5 doses 24 hours apart
Frequency of treatment:
Either a single dose or 5 times
Post exposure period:
In the acute study: 6 hr, 24 hr, 48 hr; in the subchronic study 6 hours
Doses / concentrations
Remarks:
Doses / Concentrations:
30, 2500, and 5000 mg/kg
Basis:
actual ingested
No. of animals per sex per dose:
In the acute study 15 males/dose (5 males for each of 3 sacrifice time intervals); in the negative control group 3 males/each sacrifice time interval; in the positive control group 5 males sacrificed 48 hours post-dosing.
In the subacute study 5 males/dose.
Control animals:
yes
Positive control(s):
triethylenemelamine

- Route of administration: intraperitoneal
- Doses / concentrations: 0.3 mg/kg bw

Examinations

Tissues and cell types examined:
Bone marrow
Details of tissue and slide preparation:
DETAILS OF SLIDE PREPARATION:
Colcemid (4 mg/kg ip) was administered to each animal 2 hr prior to sacrifice. Bone marrow was removed from one femur, cells isolated by centrifugation, fixed with absolute methanol:glacial acetic acid (3:1) and Giemsa-stained smears prepared for subsequent microscopic evaluation. 

METHOD OF ANALYSIS:
Fifty metaphase spreads from each animal were examined under oil immersion (x40, x63 or x100) and scored for chromatid gaps and breaks, chromosome gaps and breaks, reunions, cells with greater than 10 aberrations, polyploidy, pulverization and any other chromosomal abnormality. Mitotic indices were obtained  by counting at least 500 cells, and the ratio of the number of cells in mitosis to the total number of cells observed was expressed as the mitotic index.
Statistics:
No statistical analysis was apparently applied to the results of this study.

Results and discussion

Test results
Sex:
male
Genotoxicity:
negative
Toxicity:
no effects
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
RESULTS OF RANGE-FINDING STUDY
- Dose range: a single dose of 10000 mg/kg bw
- Clinical signs of toxicity in test animals: none

RESULTS OF DEFINITIVE STUDY
The mitotic indices for the treated animals (4 - 8%) were lower than those of the negative controls (9 - 12%) but this difference did not appear biologically significant. The three treatment groups were within the historical range of negative controls with respect to breaks (0-6%). One dicentric chromosome was noted 24 hr post-treatment with 5000 mg/kg propylene glycol, but this was considered a random event since this type of damage was also observed in the vehicle controls. Furthermore, there was no evidence of chromosomal reunion at the other time-points in this or the lower treatment groups. No other aberrations were present in the treated or vehicle control groups. The positive control group contained 36% cells with aberrations, including severe chromosomal damage (>10 aberrations / cell), breaks and reunions).

Applicant's summary and conclusion

Conclusions:
CL-Freetext:
Propylene glycol produced no detectable aberrations in
metaphase chromosomes from bone marrow when administered
orally to rats as a single treatment at doses up to 5000
mg/kg.