Tissue organ distribution and behavioral effects of platinum following acute and repeated exposure of the mouse to platinum sulfate.

Platinum sulfate was administered intragastrically (IG) to adult male Swiss mice in a single dose at the 7 day LD5 or LD25 level. Control groups received 0.25M H2SO4 (pH 0.85) or 0.14M NaCl. Open field behavior (ambulations, rearings) was measured, and tissue/organ Pt levels determined at 4 hr, or 1, 3, or 7 days post administration. At all times, the LD25 depressed ambulations significantly and rearings marginally. It did not effect exploratory ("hole-in-board") behavior. The LD25 resulted in disproportionately high tissue Pt levels relateive to the LD5. There were significant inverse correlations between behavior and tissue Pt levels for most tissues, but not for brain. In related experiments, adult male mice were subjected to repeated IG administration of Pt(SO4)2 at the LD1 level (one dose every 72 hr for up to 10 doses). Three days after administration of the final dose of each series, open-field and exploratory performance were measured and tissue/organ Pt levels determined. Tissue/organ Pt levels were variable but generally increased with dose number. No Pt was detected in the brain. Activity and explorations were marginally depressed. Only rearings correlated significantly with tissue Pt levels.

Effects on the postnatal development of the mouse of preconception, postconception and/or suckling exposure to manganese via maternal inhalation exposure to MnO2 dust.

Female mice were exposed either to MnO2 dust (7 hours/day, 5 days/week) or filtered air (control group) for 16 weeks prior to conception. On day 1 of gestation, half of each of these groups was assigned randomly either to MnO2 dust or filtered air exposure until day 17 of gestation. To separate effects of prenatal maternal exposure to MnO2 from postnatal exposure of offspring to Mn via suckling, a complete fostering/-cross-fostering design was employed. Compared to control mothers, mothers exposed to MnO2 prior to conception produced significantly larger litters. Prenatal exposure resulted in reduced neonatal activity scores and retarded offspring growth that persisted into adulthood. Offspring reared by mothers exposed to MnO2 prior to conception and filtered air postconception had significantly lower day 7 postpartum weights compared to offspring reared by mothers exposed to filtered air both prior to and postconception. Also, offspring reared by mothers exposed to MnO2 prior to conception and filtered air postconception had higher day 12 activity scores compared to offspring reared by mothers exposed to filtered air prior to conception and MnO2 postconception. Prenatal exposure to MnO2 depressed neonate activity and continued exposure, via suckling, intensified this depression. Offspring exposed prenatally to MnO2 were retrieved faster than control offspring. Rearing frequency, exploratory behavior, and scores in tests having an activity component were depressed for sexually mature offspring who had been exposed to MnO2 both in utero and via suckling. Independent of in utero exposure history, sexually mature offspring reared by mothers exposed to Mn had significantly reduced cerebellum + brain stem mitochondrial Mn levels. Also, sexually mature offspring of mothers exposed to filtered air that were reared by MnO2 -exposed mothers had lower cerebral mitochondrial Mn levels than offspring of control mothers reared by control foster mothers.

Uptake, distribution and behavioral effects of inhalation exposure to manganese (MnO2) in the adult mouse.

Adult male mice were exposed either to sublethal levels of MnO2 dust or filtered air (control group) 7 hours/day, 5 days/week for 16 to 32 weeks. Following a 16 week initial exposure period, randomly selected samples (8 animals) from both the control and Mn-exposed groups were observed for behavioral performance (ambulations and rearings in the open-field, "hole-in-board" explorations, rotarod) and learning (passive avoidance) and tissue Mn levels were determined via atomic absorption spectrometry. Exposure continued for the remaining animals and the sampling procedure was repeated biweekly for an additional 8 time points. At week 32, Mn exposure was terminated. However, biweekly testing of the remaining animals continued for an additional 3 time points. Mn-exposed animals had significantly higher blood, liver, kidney, lung, cerebrum, cerebellum plus brainstem, and testis Mn levels than control animals. With the exception of the liver, these levels declined with increasing exposure time. No histopathologic effects attributable to Mn-exposure were observed. However, significant overall effects on growth and behavior were obtained. Specifically, Mn-exposed subjects weighed more, executed more rearings in the open-field, and tended to exhibit longer latencies to enter the open-field. When the post-exposure data were analyzed separately, no significant effects were obtained. While no general relationship was obtained between tissue Mn levels and behavior, selected behavioral measures did correlate with tissue Mn levels. Animals exposed via feeding to comparable Mn levels across the same length of exposure employed in the inhalation study did not demonstrate any significant behavioral alterations.

Cerium tissue/organ distribution and alterations in open field and exploratory behavior following acute exposure of the mouse to cerium (citrate).

Cerium chloride (1:3 complex with sodium citrate) was administered to male Swiss mice (6 to 8 weeks old) either intragastrically or subcutaneously at the 7 day LD5 or LD25 level. Open field behavior (ambulations, rearings) was quantified and tissue/organ Ce levels determined at 4 hr., 1, 3 or 7 days post administration. Via the i.g. route, Ce was poorly absorbed resulting in no observable behavioral alterations and no correlations between behavior and tissue levels. Via the s.c. route, Ce significantly (p less than 0.05) depressed ambulations and rearings, mainly at short times following administration of the LD25 dose. Analogous findings were obtained in a separate study of exploratory behavior. There was a significant (p less than 0.05) correlation between open field behavior and tissue Ce levels: thus, rearings were inversely correlated with lung, stomach, cerebrum, cerebellum and brain stem Ce levels and ambulations were inversely correlated with liver, kidney, lung, blood, stomach, intestine, muscle, cerebrum, cerebellum and brain stem levels. Spleen Ce levels and ambulations were directly correlated and it is speculated that the spleen may serve a protective function in the case of Ce intoxication.