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- Table 13. Tumour Incidence in MMT Treated Mice
j.6GenotoxicityThe genotoxicity of MMT was investigated in vitro on Salmonella typhimurium strains TA98, TA100, TA1535, TA1537, TA1538 and Saccharomyces cerevisiae strain D3. MMT was tested at 1, 10, 50, 100, 500, 1000, 5000 g/plate for the S. typhimurium strains and 0.1-5% for S. cerevisiae in the presence and absence of a metabolic activator (Aroclor 1254-stimulated rat liver homogenate). Cytotoxic effects were observed in all S. typhimurium strains tested at MMT concentrations between 500-5 000 g/plate. In the presence of the metabolic activator, MMT when tested at 0.1-1% was found to reduce the survival of S. cerevisiae by approximately 50%. The survival of S. cerevisiae was doubled in the presence of 5% MMT and reduced at lower doses, in the presence of metabolic activator. MMT did not result in a significant increase in the average number of S. typhimurium histidine revertants per plate or S. cerevisiae mitotic recombinants (Ethyl Corporation 1977b). MMT was also investigated in vitro in a chromosome aberration study using Chinese hamster ovary (CHO) cells and in vivo in a micronucleus assay using C57B1 mice. MMT induced chromosomal aberrations in vitro but did not induce effects in vivo (Blakey, 1996, personal communication). A dominant lethal study was conducted on CD-1 mice. Sexually competent males were dosed via gastric intubation with MMT (80 and 160 mg/kg bw) in corn oil daily, for 5 consecutive days. On the last day of the treatment period, at least two hours after the last dosing, three untreated virgin females were placed with each male. Male and females remained together for seven days and then the females were removed and replaced with three new untreated virgins. This procedure continued for eight weeks. Males were observed daily for evidence of pharmacologic and toxicologic effects and mortality during both the exposure period and during mating. Females were sacrificed 8 days after removal from the male and the number of uterine implantations were recorded. Implantations were distinguished as early resorption sites (early fetal death), late resorption sites (late fetal deaths) and viable fetal swellings. During days 1 to 3 of the exposure period, male mice showed signs of hypoactivity, dehydration, and lacrimination. The male mortality rate at 80 mg/kg bw/day was 17% (2/12) and 23% (3/13) at 160 mg/kg bw/day. All males that died during the exposure period did so on day 3 or 4 of the treatment. Mottled liver (2/5), bright red lungs (1/5), bladder (1/5) and thoracic cavity abnormalities (1/5) were observed in the deceased males. The pregnancy rate of the MMT groups was similar to controls. There was no statistically significant difference in the mean number of early fetal deaths or viable fetal swellings per pregnant female between the negative control and MMT-treated groups. An exception occurred in week three where 80 mg/kg bw/day MMT treatment resulted in an increase in the mean number of viable fetal swellings per pregnant female. Expressed as a percentage of total implantation sites, early fetal death data were comparable between negative controls and MMT-treated groups. Exceptions were a significant decrease at week three for the 80 mg/kg bw/day MMT treatment and a significant increase at week seven for 160 mg/kg bw/day MMT treatment. These deviations from negative controls were not considered biologically significant. Ten male and 240 female mice were used per treatment. Negative and positive controls (corn oil alone and triethylenemelamine respectively) behaved accordingly. Under the conditions of the study, MMT did not cause dominant lethal effects in mice (Ethyl Corporation 1977a). j.7CarcinogenicityThe effect of MMT on lung tumour development was assessed by Witschi et al. (1981) in female A/J mice. Sixty mice were injected IP with 500 mg/kg bw urethan and sixty with 0.9% sodium chloride. One week later 30 mice from each group were given IP injections of MMT (80 mg/kg bw) in oil once a week for six weeks. The remaining 60 mice received corn oil alone. All mice were sacrificed 4 months after the first urethan injection. MMT alone or when administered repeatedly after urethan or sodium chloride treatment did not enhance lung tumour formation (Table 13). Table 13. Tumour Incidence in MMT Treated Mice
The report states that lung cell proliferation, as measured by thymidine incorporation into DNA, was reduced on day one after MMT treatment, increased by 200% above controls on day 2, was 50% higher on day 4 and normal after day 6 (no further details were provided). Directory: data -> assets -> word doc -> 0020 word doc -> Commonwealth of Australia 2002 word doc -> Commonwealth of Australia 2000 word doc -> Rail safety news issue 6 – October 2011 word doc -> Review of Multiple Chemical Sensitivity: Identifying word doc -> Board Endorsed October 2009 amended 13-09-11 with extra units 0020 -> Rail safety news issue 5 may 2011 0020 -> The arts ripple effect: valuing the arts in communities 0020 -> Monash university accident research centre report documentation page 0020 -> Section 1: Working with the Government and the Parliament 6 1Summary 6 0020 -> Bachelor of Computer Science and Bachelor of Economics (61010) Applicability of the general provisions 11 47. 1 Download 0.91 Mb. Share with your friends:
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