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5-tert-Butyl-2,4,6-trinitro-mxylol
(CAS-NR.: 81-15-2)

Ausgabe: März 2003
Stand: Oktober 2002

Genotoxicity:

There is a series of results from standard genotoxicity tests:

On the basis of these negative results there is no suspicion for a genotoxic action of musk xylene.

Carcinogenicity:

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:

There is no multigeneration study available with musk xylene.

In a 90-day study on rats with dermal applications of max. 240 mg/kg bw/day (occlusive) there were no toxic effects seen in the reproductive organs [14].

Likewise, in a chronic feeding study with musk xylene on mice with maximum dosage of ca. 200 mg/kg bw/day for 80 weeks there were also no effects seen in the reproductive organs [12].

In a peri/postnatal study on rats with exposure of the pups in utero and during lactation and subsequent mating there were no effects observed on reproductive performance (see next chapter for details of the study) [15].

Reproductive Toxicity/Development:

There has been performed a peri/postnatal study on 28 pregnant CD-rats per group with daily doses of musk xylene via gavage: 0 (control); 2.5; 7.5 and 25 mg/kg bw, respectively starting from gestational day 14 until weaning of offspring on day 21 post partum. From the litters 24 males and 24 females per group were retained to maturity and assessed for behavioural changes and for reproductive capability. The only exposure of F1 generation to musk xylene was in utero during the perinatal phase or through any transfer in the milk of the lactating dams.

Signs of maternal toxicity were only present in the 25 mg/kg bwgroup and consisted of a slightly (but statistically significant [P < 0.05] only on days 7 and 14 post partum) decreased body weight gain without concomitant reductions in absolute mean body weight.