Dietary administration of diquat for 13 weeks does not result in a loss of dopaminergic neurons in the substantia nigra of C57BL/6J mice.

Male and female C57BL/6J mice were administered diquat dibromide (DQ∙Br2) in their diets at concentrations of 0 (control), 12.5 and 62.5 ppm for 13 weeks to assess the potential effects of DQ on the nigrostriatal dopaminergic system. Achieved dose levels at 62.5 ppm were 6.4 and 7.6 mg DQ (ion)/kg bw/day for males and females, respectively. A separate group of mice was administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ip as a positive control. The comparative effects of DQ and MPTP on the substantia nigra pars compacta (SNpc) and/or striatum were assessed using neurochemical, neuropathological and stereological endpoints. Morphological and stereological assessments were performed by investigators who were "blinded" to dose group. DQ had no effect on striatal dopamine concentration or dopamine turnover. There was no evidence of neuronal degeneration, astrocytic or microglial activation, or a reduction in the number of tyrosine hydroxylase positive (TH(+)) neurons in the SNpc or neuronal processes in the striatum of DQ-treated mice. These results are consistent with the rapid clearance of DQ from the brain following a single dose of radiolabeled DQ. In contrast, MPTP-treated mice exhibited decreased striatal dopamine concentration, reduced numbers of TH(+) neurons in the SNpc, and neuropathological changes, including neuronal necrosis, as well as astrocytic and microglial activation in the striatum and SNpc.

Developmental and reproduction toxicity studies of glycolipids from Dacryopinax spathularia.

The developmental and reproduction toxicity potential of jelly mushroom glycolipids from Dacryopinax spathularia was studied in Crl:CD (SD) rats by daily oral gavage administration at doses of 150, 500 or 1000 mg/kg/day. Pregnant female rats in the developmental study received the test article from Gestation Days 6-19. F0 and F1 parental animals in the 2-generation reproduction toxicity study were dosed for a minimum of 70 days prior to mating and throughout mating, gestation, and lactation, until the day prior to euthanasia (following weaning of litters on postnatal day 21). The offspring of the F0 and F1 generations were potentially exposed to the test article in utero and via the milk while nursing. In the developmental study, there were no adverse effects on intrauterine growth and survival, or fetal morphology. In the 2-generation reproduction toxicity study, there were no adverse effects on observed parameters including macroscopic or microscopic findings, or organ weights for F0 or F1 animals, no effects on reproductive performance, and no test article-related effects on F1 and F2 postnatal survival, development, or growth. Therefore, the no-observed-adverse-effect level (NOAEL) for parental systemic toxicity, parental reproductive toxicity, and developmental/neonatal toxicity, was considered to be 1000 mg/kg/day, the highest dosage tested.