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EC number: 203-052-4
CAS number: 102-77-2
There is no reproductive toxicity screening test or generation study
available. The data from the chronic toxicity study with MBS (Monsanto
Co. 1982) were used for risk assessment.
As confirmed by literature (Mangelsdorf et al. 2003, Ulbrich & Palmer
1995, Jane ret al. 2007 and Dent 2007) histopathological examinations in
repeated dose toxicity are of high value and high sensitivity for the
evaluation of reproductive toxicity. Therefore at least for fertility
assessment a repeated dose toxicity study showing no adverse effect
should be taken into account. Also it is agreed that histopathological
changes on the reproductive organs in repeated dose studies (subacute or
longer exposure, see e.g. Ulbrich & Palmer 1995, Mangelsdorf et al.
2003) are indicative effects on fertility. Therefore repeated dose
toxicity studies should be considered as sufficient information for a
DNEL calculation for fertility if histological examination of the
reproductive organs is covered by repeated dose toxicity studies and the
mode of action of the test substance doses not give evidence for a
specific toxicity (which is not the case with MBS). For such an approach
additional assessment factors are not needed as no or only small
differences in NOAELs between e.g. two-generation studies and subchronic
studies were observed in a retrospective analysis and two-generation
study has had little impact on changing the overall NOAEL already
available from a subchronic or chronic study. Therefore it is proposed
by the group of researchers that in the absence of a two-generation
study the NOAEL obtained from a subchronic or chronic study could be
used as a reference point for deriving the DNEL (Janer et al. 2007).
In the chronic feeding studies (Monsanto Co. 1982, for more details see
endpoint repeated dose toxicity) the reproductive organs and associated
organs (ovaries, testes, prostate, and uterus) were histological
examined in all control animals and all animals of the highest dose
group (400 mg/kg bw and day). No adverse effects of the test substance
MBS on these organs was indicated. However, a significant increase in
relative gonad weights was indicatives for males of the highest dose
group, but this change was considered to be a secondary effect.
Therefore, for MBS a NOAEL fertility (400 mg/kg bw and day) based from
data of the chronic toxicity study (Monsanto Co. 1982) could be used for
Developmental toxicityThe developmental toxicity of the test substance MBS was evaluated in a teratology study with Sprague-Dawley rats (Monsanto Co. 1981). Treatment with the test substance produced a slight increase in hair loss in all treatment groups, a dose related increase in matting and staining of the anogenital haircoat in the 300 and 1000 mg/kg bw and day treatment groups. In addition, a decrease in mean maternal body weight gain during the treatment period was observed in the 300 and 1000 mg/kg bw and day treatment groups. The test substance did not produce a teratogenic response when administered orally by gavage to pregnant rats at a dose level of 1000 mg/kg bw and day. Thus, based on the findings of this study a NOAEL maternal of 100 mg/kg bw and day and a NOAEL developmental toxicity of 1000 mg/kg bw and day are suggested.
The developmental toxicity potential of MBS was evaluated in teratology
study with Sprague-Dawley rats. Dosage levels of 0, 100, 300 and 1000
mg/kg bw and day were administered orally by gavage as a single daily
dose on day 6 through 15 of gestation. Cesarean sections were performed
on all surviving dams on gestation day 20. A slight increase in hair
loss was noted in all treatment group compared to control. Matting and
staining of the anogenital hair coat was seen in the 300 and 1000 mg/kg
bw and day treatment groups. A decrease in mean maternal body weight
gain during the treatment period was observed in the 300 (-15 %) and
1000 mg/kg bw and day (-30 %) treatment groups. No biologically relevant
or statistically significant differences in the mean numbers of corpora
lutea, total implantations, viable foetuses, early or late resorptions,
postimplantation loss, mean foetal body weights, or mean foetal sex
distribution in the treated groups were noted when compared to the
control group. In addition, there were no biologically relevant or
statistically significant differences in the number of litters with
malformations in the treated groups when compared to the control group.
In conclusion, maternal toxicity of the test substance was noted at 300
and 1000 mg/kg bw and day, indicated by matting and staining of the
anogenital haircoat and a decrease of body weight gain during the
treatment. The test substance MBS did not produce a teratogenic response
when administered orally by gavage to pregnant rats at a dose level of
1000 mg/kg bw and day or less. Thus, based on the findings of this study
a NOAEL maternal of 100 mg/kg bw and day and a NOAEL developmental
toxicity of 1000 mg/kg bw and day are suggested.
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