zurück

4'-tert-Butyl-2',6'-dimethyl-3',5'-dinitroacetophenon
(CAS-N R.: 81-14-1)

Ausgabe: März 2003
Stand: Oktober 2002

Genotoxicity:

Musk ketone was negative in several in vitro tests (bacterial gene mutation tests, SOS chromotests, a mammalian gene mutation test, micronucleus test and SCEs in mammalian cells, and an UDS test). a chromosomal aberration test in mammalian cells in vitro provided an equivocal result, but as an in vivo mouse micronucleus test was negative, it can be concluded that musk ketone is not an in vivo mutagen.

Carcinogenicity:

There are no carcinogenicity data for musk ketone.

The analogous substance musk xylene Musk xylene has been tested for carcinogenicity in B6C3F1-mice by dietary administration in one experiment with a duration of 80 weeks plus 10 weeks post observational period [12]. Both dose levels tested (0.075 and 0.15 %) resulted in statistically significantly increased incidences of hepatocellular adenomas in both sexes and of hepatocellular carcinomas in males. The incidence of Harderian gland adenomas was also statistically significantly increased in males at both dose levels. Some other tumours, like lung adenomas in both sexes and lymphomas and Harderian gland adenomas in females, occurred in greater number in the treated groups but the differences with control incidences were not statistically significant. The lowest dose tested, 0.075 %, equivalent to 70-125 mg/kg bw/day in male mice and 80-143 mg/kg bw/day in female mice, is an effect dose.

*) Tamano et al. [13] (Control incidences for animals sacrificed between weeks 79 to 104 of experiment)
**) Tumors of the Harderian gland appeared in historical controls after an experimental duration of 105 weeks only

In consideration of the historical control data obtained with the same mouse strain and delivered from the same supplier in Japan [13] it is quite evident that the incidences of hepatocellular carcinomas of animals of both dose groups lie within the frame of the historical data especially if the age of the animals at sacrifice is considered. In this study the surviving animals were already sacrificed after 90 weeks. The increased incidences for Harderian gland adenomas in the actual control group as well as in the two dose groups are somewhat strange since this type of tumour appeared in the historical controls only after 105 weeks duration of experiment. Even more notable is the comparably high incidence for Harderian gland carcinomas (2 %) in control males and in low dose males (i.e 1 male affected in each of these groups) in light of the very low historical control incidence (0.4 %; 1 from 244 males affected) and the normally late appearance of this tumor type in the terminal phase of study [13].

Reproductive Toxicity/Fertility:

With respect to fertility no multigeneration reproductive toxicity study was available for either route.

In the 90-day dermal toxicity study with rats, musk ketone caused no effects on the reproductive organs [16].

In a rangefinding teratogenicity study groups of 8 pregnant Sprague-Dawley rats received by gavage 0, 60, 200, 600 or 2000 mg musk ketone (in corn oil)/kg bw/day during days 7-17 of gestation. At day 20 of gestation the animals were sacrificed. Observations after caesarean sectioning showed decreases in litter sizes and live fetuses and increases in early and late resorptions and percent resorbed conceptuses at 200 mg/kg bw and higher [18].