Registration Dossier

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:
supporting study
Study period:
1996
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study similar to OECD guideline 474.

Data source

Reference
Reference Type:
publication
Title:
Genotoxic and/or Epigenetic Effects of some Glycol Ethers: Results of different short-term tests
Author:
Elias, Z. et al.
Year:
1996
Bibliographic source:
Published inOccupational Hygiene, 2: 187-212

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
GLP compliance:
not specified
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 2-propylene glycol-1-methyl-ether
- Analytical purity: 98%
- Impurities (identity and concentrations): 0.0 mg/l peroxide
- Composition of test material, percentage of components: alpha isomer: 98.1%, beta isomer: 1.2%
- Isomers composition: as described above
- Purity test date: not specified in the report
- Lot/batch No.: not specified in the report
- Expiration date of the lot/batch: not specified in the report
- Stability under test conditions: not specified in the report
- Storage condition of test material: not specified in the report

Test animals

Species:
mouse
Strain:
CD-1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories
- Age at receipt: 7-10 weeks old
- Weight at receipt: approximately 25 g
- Housing: not specified in the publication
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: according to guideline

ENVIRONMENTAL CONDITIONS
- Temperature (°C): standard conditions
- Humidity (%): standard conditions
- Air changes (per hr): standard conditions
- Photoperiod (hrs dark / hrs light): standard conditions

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
alpha-PGME was diluted in Hank's balanced salt solution (HBSS), pH 7.2
Details on exposure:
alpha-PGME was diluted in Hank's balanced salt solution (HBSS), pH 7.2 and the test doses were administered at a volume of 0.2 ml, intraperitoneally (single injection). The negative control animals were treated with HBSS and the positive group with cyclophosphamide at dose of 25 mg/kg body weight.
Duration of treatment / exposure:
single injection
Frequency of treatment:
once
Post exposure period:
24, 48 and 72 hours
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
2500 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
4000 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
5000 mg/kg
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
6000 mg/kg
Basis:
nominal conc.
No. of animals per sex per dose:
4 males + 4 females
Control animals:
yes, concurrent vehicle
Positive control(s):
The positive group with cyclophosphamide at dose of 25 mg/kg body weight.

Examinations

Details of tissue and slide preparation:
The 2 femurs were removed from each animal and bone marrows were flushed out with 0.2 ml FCS into a tube containing FCS. The cell suspensions in 2 ml FCS were 1/100 diluted in Hanks PBS, pH 7, and spun down onto the slide at 650 rpm for 5 minutes. Two patches/slide and two slides/animal were made. The slides were air-dried, fixed for 3 minutes in absolute methanol and stained with May-Grunwald's stain.
Evaluation criteria:
The slides were coded prior to scoring. At least 1000 polychromatic erythrocytes (PCE) per animal were scored and the micronucleated PCE were counted. In addition, the ratio of PCE to mature normochromatic erythrocytes were determined by counting approximately 2000 eryhthrocytes
Statistics:
standard statistical methods

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
yes
Vehicle controls validity:
valid
Negative controls validity:
not specified
Positive controls validity:
valid
Additional information on results:
At the highest dose of 6000 mg/kg, mortality (3/8) was observed at 48 hours.

Any other information on results incl. tables

Table 1: Results of micronucleus test

Compound Dose Micronucleated PCE (ppt) PCE/NCE ratio
P GME   24 hours 48 hours 72 hours 24 hours 48 hours 72 hours
  2500  0.11 (0.10)  0.54 (0.28)  1.17 (0.07)  1.30 (0.07) 
  4000  0.36 (0.18)  0.33 (0.16)  1.06 (0.07)  1.22 (0.09) 
  5000  0.12 (0.10)  1.03 (0.33)  1.04 (0.05)  1.03 (0.23) 
  6000  0.53 (0.20)  0.69 (0.42)  0.96 (0.09)  0.60 (0.20) 
 Hanks 0.53 (0.27)  1.33 (0.09) 
 CP 25  9.90 (1.33)  1.27 (0.07) 

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
There was no increase in the frequency of micronuclei in polychromatic erythrocytes harvested from bone marrow of mice treated with propylene glycol methyl ether and hence the test material was classified as negative
Executive summary:

2-propylene glycol-1-methyl-ether was evaluated for gentoxicity in a micronucleus test in mice at doses from 2500 - 6000 mg/kg and there was no increase in the frequency of micronuclei in polychromatic  erythrocytes harvested from bone marrow of mice treated with PGME and hence PGME was classified as negative