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46210605.der.pdf
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46210605
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Methylazoxy methanol acetate
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592-62-1
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667001
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Kaufmann, W.; Schneider, K.; Ravenzwaay, B. (2003) Methylazoxy Methanol Acetate: Positive Control - Developmental Neurotoxicity Study in Wistar Rats Single Intraperitoneal Administration to the Dams: Final Report. Project Number: 2003/1022852, 03R0076/02004. Unpublished study prepared by BASF Aktiengesellschaft. 867 p.
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2003.0
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Methylazoxy methanol acetate (MAM): In a developmental neurotoxicity study (MRID 46210605), Methylazoxy methanol acetate (MAM) (>96% a.i.; batch # ET11-109-1) was administered to 42 presumed-pregnant female Wistar (Crl GlxBrl Han:WI) rats per dose by a single intraperitoneal administration at dose levels of 0, 7.5, 15, or 30 mg/kg bw on gestation day (GD) 15. An open field observation was performed on 10 dams/group on GDs 7 and 16 and on lactation days 7 and 14. On postnatal day 4, litters were culled to yield 8 pups/litter (assumed 4/sex/litter, but not stated). Offspring representing 20 litters/dose were allocated for detailed open field observation, assessment of motor activity, assessment of auditory startle response habituation, and assessment of learning and memory. On PNDs 11, 22, and 62, the whole brain was collected from 10 pups/sex/dose for micropathological examination and morphometric analysis. These pups were also examined for neuropathology.
Effects in the maternal rats were limited to reduced body weight gain (over GDs 15-20 and 1-20) and feed consumption (over GDs 15-20 and lactation days 1-7).
Treatment-related and dose-dependent effects noted in the offspring included: gross lesions at the mid- and high-dose (hypoplasia of the cortex, cerebri), neurohistopathological lesions at the high-dose (disorganization of the cortical layers, clusters of ectopic hippocampal and periventricular neurons, and ventricle dilation), decrements in brain weight compared to controls (absolute and relative brain weights; low-, mid- and high-dose males; mid- and high-dose females), and a dose-related reduction in morphometric measurements (greatest reductions occurring in the corpus callosum, the hippocampus, the parietal and the frontal cortices; low-, mid, and/or high-dose groups affected). Basal ganglia (nucleus caudatus/putamen) and the cerebellum (folium pyramis, external germinal matrix layer) also showed reduced size, indicating a treatment-related influence on the development of the brain.
Corresponding with the morphological abnormalities, increased motor activity, impaired auditory habituation, and retarded learning/relearning capability were noted at the mid- and high-dose. The neurotoxic effects did not become apparent until the affected offspring had developed to late postweaning (PND 60). Females appeared to be more sensitive.
This study is classified Acceptable/Non-guideline. BASF Corporation has demonstrated proficiency in this study for detecting changes in FOB, Motor Activity, Auditory Startle, Learning-memory, Neuropathology and Brain Morphometry in Wistar (Crl GlxBrl Han:WI) rats (treated pre-weaning, tested pre- and postweaning) due to Methylazoxy methanol acetate (MAM) treatment for the time period around 2002 (in life period of study). This positive control study does not satisfy any guideline requirement. Although analytical determination of the stability, homogeneity and concentration of the test formulations was not performed, the deviations did not affect the acceptability of the study.
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Developmental-Neurotoxicity
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NA [83-6, Developmental Neurotoxicity|870.6300, Developmental neurotoxicity study]
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Intraperitoneal
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No Duration Period; Positive Control Study
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54594.0
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2012-03-20
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2018-06-06
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Added by
Madison Feshuk
on Apr 25, 2022
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