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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Genetic toxicity: in vivo

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Administrative data

Endpoint:
in vivo mammalian cell study: DNA damage and/or repair
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
test procedure in accordance with national standard methods with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1991

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method:
- according to Butterworth, B.E. et al. (1987). A protocol and guide for the in vivo rat hepatocyte DNA repair assay. Mutation Research 189, 123-133 (hepatocyte DNA-repair assay)
- according to Bermudez and Allen (1984). The assessment of DNA damage and repair in rat nasal epithelial cells. Carcinogenesis 5: 1453-1458 (respiratory epithelial cells assay)
GLP compliance:
not specified
Type of assay:
unscheduled DNA synthesis

Test material

Constituent 1
Chemical structure
Reference substance name:
1,4-dioxane
EC Number:
204-661-8
EC Name:
1,4-dioxane
Cas Number:
123-91-1
Molecular formula:
C4H8O2
IUPAC Name:
1,4-dioxane

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Lab. Inc. Raleigh NY
- Age at study initiation: 10-12 weeks
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 2 weeks


ENVIRONMENTAL CONDITIONS
- Temperature (°F): 72+/- 2
- Humidity (%): 50 +/- 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
other: oral: drinking water in combination with gavage
Vehicle:
water
Duration of treatment / exposure:
- liver hepatocytes: a single application of 1000 mg/kg bw or treatment with 1% 1,4-dioxane in drinking water for 2 weeks or treatment with 2% 1,4-dioxane for 1 week
- respiratory epithelial cells: 1% 1,4-dioxane in drinking water for 8 days, or 1% in drinking water for 8 days with an additional single gavage dose of 0, 10, 100 and 1000 mg/kg 12 h prior to sacrifice
Frequency of treatment:
continuous and once by gavage
Doses / concentrationsopen allclose all
Dose / conc.:
0 mg/kg bw/day (actual dose received)
Remarks:
1% in drinking water with an additional single gavage
Dose / conc.:
10 mg/kg bw/day (actual dose received)
Remarks:
1% in drinking water with an additional single gavage
Dose / conc.:
100 mg/kg bw/day (actual dose received)
Remarks:
1% in drinking water with an additional single gavage
Dose / conc.:
1 000 mg/kg bw/day (actual dose received)
Remarks:
1% in drinking water with an additional single gavage
Dose / conc.:
1 other: %
Remarks:
concentration in drinking water
Dose / conc.:
2 other: %
Remarks:
concentration in drinking water
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment
Positive control(s):
- hepatocyte DNA repair assay: DMN and 2-AAF
- nasal epithelial cell DNA repair assay: MMS

Examinations

Tissues and cell types examined:
liver hepatocytes and nasal epithelial cells
Evaluation criteria:
Labelled cells were recognized by by the dense pattern of silver grains overlying the nuclei, cells with a nuclei density of >= 10 were scored as undergoing replicative DNA-synthesis. The labeling index(LI) was calculated by dividing the number of labeled nuclei by the total counted.


The autoradiograms were stained and scored for the number of grains over the nucleus for 100 cells.
Statistics:
for the hepatocytes : P <= 0.05 by the Newman-Keuls multicomparison test.
for the nasal epithelium: unpaired t-test at significance level of P<= 0.05

Results and discussion

Test results
Key result
Sex:
male
Genotoxicity:
negative
Toxicity:
not specified
Vehicle controls validity:
valid
Negative controls validity:
valid
Positive controls validity:
valid
Additional information on results:
Neither a single application of 1000 mg/kg bw, nor treatment with 1% 1,4-dioxane in drinking water for 2 weeks or with 2% 1,4-dioxane for 1 week, induced unscheduled DNA synthesis in primary rat hepatocytes. Negative results for unscheduled DNA synthesis were also found in rat nasal respiratory epithelial cells (from the nasoturbinate or the maxilloturbinate) after treatment of rats with 1% 1,4-dioxane in drinking water for 8 days, or after treatment with 1% in the drinking water for 8 days with an additional single gavage dose of up to 1000 mg/kg bw 1,4-dioxane.

Applicant's summary and conclusion