Effects elicited by toxaphene in the cynomolgus monkey (Macaca fascicularis): a pilot study.

Toxaphene, which was added to glycerol/corn oil, was administered at a level of 1 mg/kg body weight/day in gelatin capsules to four healthy young adult cynomolgus (Macaca fascicularis) monkeys for 52 weeks. Four control monkeys ingested capsules containing only glycerol/corn oil. Each group had two males and two females.

Microsomal enzyme activity, glutathione S-transferase-placental form expression, cell proliferation, and vitamin A stores in livers of rats consuming Great Lakes salmon.

Male and female Sprague-Dawley rats were fed diets incorporating lyophilized chinook salmon obtained from Lake Ontario and Lake Huron. After 70 days, females were bred and the progeny (F1) were reared on the same fish-based diets as the adults (F0). After 78-133 days on the diets, males and females of both generations were sacrificed and hepatic microsomal enzyme activities determined, along with glutathione S-transferase-placental form (GSTP) expression and hepatic cellular proliferation.

30-day oral toxicity study of domoic acid in cynomolgus monkeys: lack of overt toxicity at doses approaching the acute toxic dose.

Domoic acid was orally administered to 3 cynomolgus monkeys at doses of 0.5 mg/kg for 15 days and then at 0.75 mg/kg for another 15 days.

Cancer risk assessment at the crossroads: the need to turn to a biological approach.

Mathematically based carcinogen risk assessment is based on a number of prudent default assumptions which are becoming progressively less tenable as new scientific evidence is adduced. For example, the assumptions that all rodent carcinogens will be carcinogenic in humans and that there is no safe dose of any carcinogen may, in specific examples, be shown to be untrue. The mechanisms by which carcinogens exert their effects, especially the induction of DNA lesions, DNA repair of these lesions, and cell proliferation, are considered; it is suggested that with recently developed experimental techniques they might be employed to develop a more biologically based approach to risk assessment and might avoid at least, some of the pitfalls associated with the present mathematically based carcinogen risk assessment models.

Subchronic toxicity study of domoic acid in the rat.

Male and female Sprague-Dawley rats were dosed by gavage for 64 days with 0, 0.1 or 5 mg/kg/day domoic acid. Treated animals showed no clinical abnormalities.

Capillary GC-ECD and ECNI GCMS characterization of toxaphene residues in primate tissues during a feeding study.

Toxaphene is a pesticide whose use was banned in North America because of concerns regarding its toxicity. To obtain better data on the metabolism and toxicity of toxaphene in primates, a one year feeding study was carried out in cynomologous monkeys at a dose of 1 mg/kg/day for one year. Levels of toxaphene residues in blood and adipose tissue during the dosing period were measured by GC-ECD and ECNI GCMS.

Phenolic antioxidants: Health Protection Branch studies on butylated hydroxyanisole.

Synthetic phenolic antioxidants have been added to foods for decades to retard the autooxidation of lipid that leads to rancidity. The major antioxidants, butylated hydroxytoluene (BHT) and butylated hydroxyanisole (BHA), are used in foods world wide. Recent studies suggest that BHA, and perhaps BHT, are carcinogenic to rodents.

Chronic feeding study of deoxynivalenol in B6C3F1 male and female mice.

A 2 year feeding study was conducted with male and female B6C3F1 mice that consumed diets containing 0, 1, 5, or 10 ppm deoxynivalenol (DON). Survivability was good and, while the test animals gained less weight with increasing levels of DON in the diet, there were no consistent toxic manifestations associated with DON consumption. There was some evidence for an increase in serum IgA and IgG in females, and there were sporadic changes noted in the clinical chemistry and hematology parameters conducted at the terminal sacrifice.

Long-term effects of Aroclor 1254 (PCBs) on plasma lipid and carnitine concentrations in rhesus monkey.

Sixty-seven female rhesus monkeys (Macaca mulatta) were orally dosed daily for 152 weeks with 0, 5, 20, 40, and 80 micrograms Aroclor 1254 (PCB)/kg body wt. Blood polychlorinated biphenyl (PCB) concentrations were highly positively correlated (r = 0.92, P < 0.

International Commission for Protection Against Environmental Mutagens and Carcinogens. Oxidative DNA damage--the effects of certain genotoxic and operationally non-genotoxic carcinogens.

A wide variety of oxidative DNA lesions are commonly present in untreated human and animal DNA. One of these lesions, 8-hydroxydeoxyguanosine, has been shown to lead to base mispairing (mutation) on DNA replication. Other lesions remain to be investigated in this respect.

Toxicology and seafood toxins: domoic acid.

Marine and terrestrial food sources are susceptible to contamination by various industrial chemicals and microbial pathogens. Both types of hazard are amenable to regulatory assessment using a single toxicology data base, along with some knowledge of contaminant levels and consumption figures for food. On the other hand, regulatory problems persist with acutely toxic naturally occurring phycotoxins, which may accumulate unpredictably to toxic levels in seafood.

Early indicators of potential neoplasia produced in the rat forestomach by non-genotoxic agents: the importance of induced cellular proliferation.

Forestomach neoplasia induced by the apparently non-genotoxic carcinogens, butylated hydroxyanisole and propionic acid, appears to arise by way of sustained high levels of cellular proliferation. Several other inducers of enhanced cellular proliferation, or the consequential incidence of hyperplastic lesions, have been identified in the rodent forestomach but the requisite carcinogenicity bioassays remain undone. In other tissues, such as the male rat kidney, the rodent thyroid follicular cell and the bladder epithelium, there is also evidence supporting the concept that sustained enhanced cellular proliferation may be an important early marker for non-genotoxic carcinogens.

An appreciation of the maximum tolerated dose: an inadequately precise decision point in designing a carcinogenesis bioassay?

Cancers arise in specific tissues. One difficulty with the present definitions of the Maximum Tolerated Dose (MTD), as they pertain to the rodent cancer bioassay, is that they base MTD on relatively crude parameters associated with the well-being of the entire animal rather than with the lack of specific tissue toxicity. Additional factors that could be included in the MTD definition, or could be separately determined, are addressed.

Experimental oral toxicity of domoic acid in cynomolgus monkeys (Macaca fascicularis) and rats. Preliminary investigations.

A recent outbreak of marine food poisoning in humans was attributed to the consumption of blue mussels (Mytilus edulis L.) contaminated with domoic acid (DA) that was produced by the diatom Nitzschia pungens. The clinical and morphological effects of single oral doses of extracts of mussels contaminated with DA or of DA isolated from toxic mussels were investigated in small groups (one to six) of cynomolgus monkeys (Macaca fascicularis; 0.

Acute neurotoxicity of domoic acid in the rat.

A recent outbreak of human food poisoning, characterized by severe gastrointestinal and neurologic abnormalities, with a fatal outcome in 3 patients, was attributed to the consumption of poisonous mussels containing domoic acid at an abnormally high concentration. The purpose of the present study was to determine if domoic acid, a glutamate analogue extracted from poisonous mussel, was neurotoxic to rats. Groups of female Sprague-Dawley rats were dosed once intraperitoneally with 0, 1, 2, 4, or 7.

Acute parenteral neurotoxicity of domoic acid in cynomolgus monkeys (M. fascicularis).

To study the CNS effects of domoic acid (D.A.), 6 adult Cynomolgus monkeys (M.