potassium titanium oxide (K2Ti6O13)

Additional toxicological data

Administrative data

Endpoint:

additional toxicological information

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Determination of carcinogenic potential of mineral fibers by 8-hydroxydeoxyguanosine as a marker of oxidative DNA damage in mammalian cells

Author:

Naoko Murata-Kamiya á Takao Tsutsui, Akihiro Fujino
Hiroshi Kasai and Hiroshi Kaji

Year:

1997

Bibliographic source:

Int Arch Occup Environ Health (1997) 70: 321-326

Materials and methods

Type of study / information:

in vitro study; the purpose of this study was to develop a simple method of testing the carcinogenicity of fibrous materials.

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

To streamline the experimental procedure, authors used a murine reticulum cell sarcoma, the J774 cell line, which exhibits the cytologic, adherent, and phagocytic properties of macrophages (Ralph et al. 1975).
Using high pressure liquid chromatography (HPLC) equipped with an electrochemical detector (ECD), authors have studied whether 8-OH-dG formation is induced in the cellular DNA of J774 cells incubated with the fibrous materials.
They also measured the levels of TNF produced by J774 cells.
In the present study, an attempt was made to elucidate the relationship between the biological effects of fibrous materials, 8-OH-dG formation, and TNF
production.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Dipotassium titanate(2-)

EC Number:

261-919-2

EC Name:

Dipotassium titanate(2-)

Cas Number:

59766-31-3

Molecular formula:

K.1/2O17-Ti8

Test material form:

solid: fibres

Details on test material:

no data

Specific details on test material used for the study:

potassium octatitanate: GML = 2.8 micron, GMD = 0.41 micron.

Results and discussion

Any other information on results incl. tables

Controls

The amount of 8-OH-dG in the control with crocidolite was not significantly higher than that in the control without fiber (P > 0.1).

Crocidolite is the most potent carcinogen, between the studied fibers.

Although the levels of TNF were the same in both controls, with and without crocidolite, TNF was produced with twofold higher eciency in the crocido- lite-exposed sample than in the control with crocidolite. The increases in the amount of 8-OH-dG and TNF were statistically significant (P<0.05).

Crocidolite increased the formation of 8-OH-dG in the DNA in a dose-dependent manner.

Mineral fibers

Various kind of mineral fibers (natural mineral fibers and man-made mineral fibers) were tested: the amount of 8-OH-dG in the cellular DNA of J774 cells was dfferent among the fibers. The natural mineral fibers increased the formation of 8-OH-dG more than the man-made mineral fibers.

The level of TNF produced by J774 cells was not different among the fibers. All the samples exposed to fibers, either natural mineral fibers or man-made mineral fibers, increased TNF production as compared with that of the control with crocidolite.

	8-OH-dG (per 10^5 dG)	TNF (ng/ml)
Potassium octatitanate	0.33 +/- 0.06	3.87 +/- 1.16

Applicant's summary and conclusion

Conclusions:

These results indicate that the mechanism of TNF production is different from that of 8-OH-dG formation, and that the carcinogenicity of various fibrous materials can be better evaluated by measuring the 8-OH-dG level in J774 cellular DNA after treatment with these fibers.

Executive summary:

8-Hydroxydeoxyguanosine (8-OH-dG) is a typical form of oxidative DNA damage, which causes mutations in vitro and in vivo. To develop a simple method of testing the carcinogenicity of fibrous materials, the formation of 8-OH-dG was determined in the DNA of J774 cells, an established reticulum cell sarcoma line, after treatment with various natural and man-made mineral fibers.

The amount of 8-OH-dG was determined using high-pressure liquid chromatography (HPLC) equipped with an electrochemical detector (ECD). We tested three natural mineral fibers (crocidolite, amosite, and chrysotile) and three man-made mineral fibers (ceramic, glass, and potassium octatitanate). Among them, a significant increase in 8-OH-dG formation was observed in the crocidolite- and amosite-treated cells. We also measured the amount of tumor necrosis factor (TNF) produced by J774 cells incubated with the fibrous materials. Cellular TNF production increased after treatment with all the fibers tested, but it was not sta- tistically significant except in the case of chrysotile. Therefore, these results indicate that the mechanism of TNF production is dierent from that of 8-OH-dG formation, and that the carcinogenicity of various fibrous materials can be better evaluated by measuring the 8-OH-dG level in J774 cellular DNA after treatment with these fibers.