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The primary objective of this research was to test the hypothesis that low level lead (Pb) exposure during early life leads to disruption in blood-brain barrier (BBB) function in the young rat. Newborn rats received lead via milk from lactating dams that were drinking water containing 0.1% lead acetate Pb(Ac)2. Pups were weaned to, and maintained on, 0.1% Pb(Ac)2-containing solution up to 70 days of age. Growth was no different from that of coetaneous controls. Experimental animals displayed elevated blood lead (15 microgram/dl) within 2 days from the onset of exposure, and it increased to 35-40 microgram/dl between 13 and 22 days of age. Following weaning to the higher lead source, blood lead values continued to increase (55 microgram/dl) but, then, appeared to decline after 55 days of age. Control animals consistently possessed blood lead values of less than 5 microgram/dl. The brain capillary (BBB) transport of the neurotransmitter precursors, choline and tyrosine, was studied at 55 and 70 days of age using intracarotid injections of a bolus containing 14C-labeled substrate and 3HOH as a diffusable reference (Brain Uptake Index). There was no difference in the transport of either choline of tyrosine in lead-intoxicated rats compared to controls. Suspected adverse psychoneurological effects of low level inorganic lead probably relate to the parenchymal cells of the CNS and not to the brain capillary endothelial cells.

Chloramphenicol is extracted from meat, liver, kidney and milk samples with ethyl acetate, followed by hexane partitioning with aqueous sodium chloride to remove lipids, ethyl acetate reextraction, formation of trimethylsilyl derivative of chloramphenicol and quantitation by electron capture gas chromatography. Precision, accuracy and recovery of the method was tested. The average recoveries from meat samples spiked at 25, 50 and 100 micrograms/kg levels ranged from 94.7 to 98.7% with coefficient of variation (CV) in the range 3.6-8.3%. Recovery and CV values from milk samples spiked at three levels ranged from 90.4 to 97.2% and from 4.9 to 6.6%, respectively. The detection limit of the method was 5 micrograms/kg.

Milk from lactating goats fed tansy ragwort (Senecio jacobaea) was evaluated for its ability to influence hepatic drug metabolism. The milk after being freeze-dried was fed to male rats for 1 week ad lib. A significant reduction in the activities of hepatic aminopyrine N-demethylase and aryl hydrocarbon hydroxylase was obtained. There was no significant change in the activities of microsomal epoxide hydrolase and cytosolic glutathione S-transferase. The data suggest that consumption of milk from goats fed Senecio jacobaea produces a selective alteration of the activities of hepatic drug-metabolizing enzymes.

Whole milk, skim milk, lactose, and milk protein and lipid fractions in concentrations in milk were heat treated, then admixed with concentrated chlorine based sanitizer to give 1.34 g sodium hypochlorite per liter of solution. After 24-h reaction at ambient temperature, .1 ml of well dispersed control and reacted samples were injected into fertile chicken eggs by the technique of Duthachie and Fletcher. Control samples were prepared, refrigerated, warmed to ambient temperature, and well shaken just before injection into fertile eggs. Mortality assessed each week during incubation and hatchability served as indices of toxicity. Chlorinated whole milk showed increased toxicity as compared to control whole milk; however, milk lipid fractions were less toxic when chlorinated. All other chlorinated samples were equal to or less toxic than samples of nonchlorinated control milks and milk fractions.

Samples of whole milk were heat treated by commercial heat-sterilization, by commercial heat-pasteurization or by a laboratory heat-pasteurization (65 degrees C for 30 min). Each sample was tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 with and without S-9 mix. Dichloromethane extracts of milk heated at 100, 135 and 150 degrees C for 5 hr were also tested for mutagenicity using the same assay. None of these samples exhibited mutagenicity in the Ames assay used.

In the present study the effects of perinatal diazepam (DZP) exposure on behavior and benzodiazepine binding site characteristics in offspring were investigated. Pregnant F344 rats were treated during the last trimester of gestation with vehicle or diazepam (3 mg/kg, 5 mg/kg, or 10 mg/kg). Lactating dams were similarly treated on postnatal days 1-7. Both prenatal and postnatal exposure to diazepam resulted in significant effects on the acquisition and extinction of active avoidance behavior measured postweaning. The number of trials to extinction of one-way active avoidance behavior was significantly greater in offspring exposed gestationally to 3 mg/kg and 10 mg/kg diazepam and postnatally to 10 mg/kg diazepam. The mean response latencies for all diazepam treated groups were significantly shorter than those of the vehicle treated rats during the first 15 trials under extinction conditions. In contrast, neither gestational nor postnatal diazepam exposure significantly affected either acquisition or retention of a passive avoidance task. In addition, the binding affinity between the benzodiazepine type I selective ligand, CL218,872, and cortical membranes, as well as the degree to which GABA potentiated 3H-flunitrazepam were significantly altered by perinatal diazepam exposure. No treatment altered the approximate number of benzodiazepine binding sites in either the cortex, hippocampus, or cerebellum. The results of this study further support diazepam as a behavioral teratogen and give new evidence for neurochemical effects following gestational as well as postnatal diazepam exposure.

Mice were gavage-fed on day 13 of pregnancy with 0 (groups N, 15, 25) or 25 (group P) mg/kg of secalonic acid D (SAD) and again while nursing their offspring on postgestational days 1-10 with 0 (N,P), 15(15) or 25(25) mg/kg/day. SAD residues were present in the stomach of pups nursed by SAD-treated dams. Postnatal exposure to SAD decreased (P less than 0.05) body weight gains of offspring. Treatment decreased the developmental levels of norepinephrine and dopamine in the prosencephalon (forebrain) and cerebellum-pons of the offspring on postnatal days (PND) 7 and 7-16, respectively. On PND 7-16 serotonin and 5-hydroxyindoleacetic acid levels decreased in the prosencephalon and cerebellum-pons of offspring exposed prenatally (P) or postnatally (15,25) to SAD.

The effects of d-amphetamine on several measures of activity and spontaneous alternation were evaluated in rats chronically exposed to a low level of lead acetate via maternal milk during the neonatal period. Alterations in the amphetamine responses of lead-treated rats were observed with some measures of activity and exploration but not with others. 'Paradoxical' responses were observed with postural rearing and spontaneous alternation. No drug response was seen in lead-treated animals with respect to center field activity in contrast to a large increase seen in controls. Normally, amphetamine reduces grooming behavior, but since this reduction was greater in lead-reared than in control rats, the data suggest that for this measure the lead-reared rat may posses an increased sensitivity to amphetamines. These results were discussed in terms of the behavioral parallels found between lead poisoning and childhood hyperactivity, and the potential of this model as an animal analog of minimal brain dysfunction hyperactivity.

4-methylimidazole (4-MI) was given orally to a cow in increased dosages to determine if it could be detected in her milk and be present at a concentration high enough to affect her nursing calf. 4-MI was found in the milk, but the calf remained clinically normal throughout the experiment. The cow died after the fourth dose of 20 g 4-MI. Four groups of 10 mice each were given oral doses of water, normal milk, cow's milk after low doses of 4-MI, or cow's milk after high doses of 4-MI. All mice remained healthy after a 2-week feeding trial. Six 3-day-old calves were given 4-MI directly in their bottles of milk up to 2 times the highest level found in toxic feed with only mild depression noted in one calf. Two pregnant cows were given 4-MI pre-partum to determine if it would get into the colostrum at higher levels. Both cows received 4-MI 3 days before they calved and for 2 weeks afterward. Cow A exhibited trembling, excessive salivation and incoordination after the initial dose. Cow B and the newborn calves were never affected throughout the experiment. Each time the dose of 4-MI reached 1.5 g or more, Cow A would exhibit the previously described signs. 4-MI was detected in the colostrum but not in higher concentrations than in the other milk samples.

Tansy ragwort (Senecio jacobaea ) was evaluated for animal and human health hazard using the Salmonella/mammalian-microsome mutagenicity test. An acetone extract of tansy ragwort (TR) produced a negative mutagenic response for bacterial tester strains TA1535 and TA100 and a toxic response in tester strains TA1537 and TA98. Assay of this extract in the presence of mammalian liver microsomes (S-9) resulted in positive mutagenic responses in tester strains TA1535, TA1537, TA98 and TA100. Species differences were evaluated by use of liver microsome preparations from induced rat and uninduced sheep, beef, hamster, trout and rat. Only a slight species difference was demonstrated. A mixture of pyrrolizidine alkaloids (PA), extracted from TR flowers, produced a negative response in tester strains TA1535, TA1537, TA98 and TA100. A negative response was also demonstrated when the TR flower PA mixture was assayed with the Salmonella tester strains and induced rat liver microsomes ( IRLM ). A mixture of PA extracted from Senecio longilobus also produced a negative response. The major PA present in TR, jacobine , produced a negative response without and with IRLM exposure in tester strains TA1535, TA1537, TA98 and TA100. Another similar PA, monocrotaline, found in various Crotalaria species also gave a negative response. Milk from TR-fed goats was evaluated for mutagenic response. Milk from goats not receiving TR and from goats receiving TR at a level of 1% of their body weight/day via rumen cannula produced a negative response without liver microsomes present. Milk from TR-fed goats, however, yielded both negative and marginally positive responses for different combinations of tester strains and liver microsome preparations.

To examine the safety of foods (meat and milk) obtained from animals whose feeds were preserved with allyl isothiocyanate (AITC), the authors investigated the status and development of animals, some aspects of protein, lipid and carbohydrate metabolism, some enzymes, hemopoiesis and reproduction function of Wistar rats fed diets containing the above products (55 g dry milk or 50 g boiled meat per 100 g diet). To measure the residual quantity of allylamine (AA), the main metabolite of AITC, a chromato-fluorometric method with the use of dansyl chloride was devised, permitting the detection of 2 ng AA in the spot. The relative standard deviation was 0.14-17. The degree of AA extraction amounted to 96%. The method made it possible to detect the residual quantity of AA in the kidneys (up to 12.2 +/- 2.0 micrograms/kg) and in the liver (up to 83.1 +/- 12.4 micrograms/kg). The data obtained evidence that AA cannot be used as conservant for manufacturing feeds for agricultural animals.

The role of metabolic activation/deactivation reactions during development is evaluated in relation to developmental pharmacology and toxicology. Enzyme systems evaluated include the mixed-function oxidases (aryl hydrocarbon hydroxylase and oxidative demethylation), epoxide hydration and conjugation (glutathione conjugation, sulfation, and glucuronidation). Placental transfer and milk secretion of chemicals are discussed in relation to maternal, placental, and fetal metabolism. Normal patterns of enzyme development can be modified in two ways: (1) enzyme induction and (2) enzyme imprinting. Postnatal induction of the mixed-function oxidases and glucuronyl-transferase following treatment of pregnant rats with TCDD is shown to be caused primarily by newborn exposure to TCDD in milk. Structure-activity relationship are defined for the perinatal induction of hepatic enzymes by the pure PCBs. PCBs are divided into two classes: P-450 inducers and P-448 inducers. Imprinting or programming of hepatic metabolism is a function of the sexual differentiation of enzyme activity; male and female activities are similar in prepubertal animals, whereas pronounced sex differences are evident in adults. Treatment of newborn rats (days 2--6) with diethystilbestrol or testosterone resulted in a feminization (decrease) of mixed-function oxidation and glucuronidation in adult males. No changes were seen in immature males or females or adult females. This effect appears to be irreversible and is under pituitary-hypothalamic-gonadal control. In addition to the feminization of enzyme activity, neonatal exposure to hormonally active chemicals also feminizes the hepatic response to cadmium in resultant adult animals.

The authors studied behavioral responses, conditioned reflexes and indices of protein synthesis in the structures of the brain in the progeny of female rats which received ethanol during the period of lactation.