Reproductive toxicity of ergot alkaloids in mink.

Ergot alkaloids are-synthesized by fungi of the Claviceps family that infect rye as well as other cereals and grains. Since a portion of the ranch mink diet is cereal, mink are at a risk of being exposed to ergot alkaloids. This study was performed to determine the reproductive toxicity of ergot alkaloids derived from ergot-contaminated oats in mink. Four groups of 12 female mink each were fed diets containing 0, 3, 6 or 12 ppm ergot alkaloids from 2w prior to the breeding season until the kits were approximately 33-d old (133 d). Females were mated with untreated males. Ergo talkaloids caused a transient decrease in feed consumption, but body weights were unaffected. The gestation period of the mink in the 6 ppm group was longer compared to controls. The number of mink whelping varied significantly with 9 mink whelping each in the control and 3 ppm groups compared to 4 mink in the 6 ppm group and 1 in the 12 ppm group. Ergot alkaloids had a significant effect on kit survivabilitywith no kits surviving in the 12 ppm group. Serum prolactin was significantly depressed in the 3 ergot alkaloid groups compared to the control group. This study indicated that ingestion of ergot alkaloids at 3 ppm or higher resulted in reproductive toxicity in mink.

Health effects following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards.

Permanent approval of shot composed of tungsten-iron and tungsten-polymer for waterfowl hunting by the U.S. Fish and Wildlife Service was pending the results of the present study that examined the health and reproductive effects of the two shot types on mallards (Anas platyrhynchos) over a 150-day period. We collected data pertaining to the effects of tungsten-iron and tungsten-polymer shot on mortality, body weight, organ weight, tissue pathology, and shot erosion. Thirty-two bird groups (sexes equal) of adult mallards were dosed orally with eight #4 steel shot (control), eight #4 tungsten-iron shot, or eight #4 tungsten-polymer shot on days 0, 30, 60, 90, and 120 of a 150-day trial (26 January 1998 to 25 June 1998). An additional 12 mallards (sexes equal) were dosed orally with eight #4 lead shot (positive control) on day 0 of the study. All lead-dosed ducks died by day 25, whereas no ducks died in the other treatment groups. Significant liver hemosiderosis was present in all control and tungsten-iron-dosed males, in five of eight control and three of eight tungsten-iron-dosed females, and in one tungsten-polymer-dosed male examined. The rate of shot erosion was highest for tungsten-polymer shot (99%), followed by tungsten-iron (72%), and steel (55%) shot. Tungsten-iron or tungsten-polymer shot repeatedly administered to adult mallards did not have deleterious health effects during the 150-day trial based on mortality, body weights, organ weights, and histology of the liver and kidneys.

Reproductive effects and duckling survivability following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards.

Tungsten-iron and tungsten-polymer shot were given conditional approval for waterfowl hunting by the U.S. Fish and Wildlife Service based partly on the results of a 30-day acute toxicity trial utilizing mallards (Anas platyrhynchos). Final approval of the two tungsten-containing shot was contingent on the results of a 150-day study that assessed the health and reproductive effects of tungsten-iron and tungsten-polymer shot in adult mallards. Reproductive data are presented in this paper. Sixteen male and 16 female adult mallards were dosed orally with eight #4 steel shot (control), eight #4 tungsten-iron shot, or eight #4 tungsten-polymer shot on days 0, 30, 60, 90, and 120 of a 150-day trial (26 January 1998 to 25 June 1998). Reproductive performance was assessed during the last 90 days (day 61 to day 150) of the trial. There were no significant differences in egg production and fertility and hatchability of eggs from tungsten-iron- and tungsten-polymer-dosed ducks compared to control ducks. There was no evidence of differences in percent survivability and body weight of ducklings from tungsten-iron and tungsten-polymer mallards compared to ducklings from control ducks. Tungsten-iron or tungsten-polymer shot repeatedly administered to adult mallards during the 150 day trial did not adversely affect reproduction or their offspring.

Hematological effects and metal residue concentrations following chronic dosing with tungsten-iron and tungsten-polymer shot in adult game-farm mallards.

The U.S. Fish and Wildlife Service required a chronic dosing study that assessed the health and reproductive effects of tungsten-iron and tungsten-polymer shot in adult game-farm mallards (Anas platyrhynchos) prior to granting permanent approval of the shot for waterfowl hunting. Herein, we present the effects of tungsten-iron and tungsten-polymer shot on various hematologic parameters and metal residue concentrations in the femur, liver, kidneys, and gonads. Thirty-two-bird groups (sexes equal) of adult mallards were dosed orally with eight #4 steel shot (control), eight #4 tungsten-iron shot, or eight #4 tungsten-polymer shot on days 0, 30, 60, 90, and 120 of a 150 day trial (26 January 1998 to 25 June 1998). An additional 12 mallards (sexes equal) received eight #4 lead shot (positive control) on day 0 of the study. Lead-dosed mallards had significantly decreased hematocrit, hemoglobin concentration, and whole-blood delta aminolevulinic acid dehydratase activity on day 7, as well as significant changes in a number of plasma chemistry parameters compared to ducks in the control, tungsten-iron, or tungsten-polymer groups. Mallards dosed with tungsten-iron or tungsten-polymer shot had occasional significant differences in hematocrit and plasma chemistry values when compared to control mallards over the 150 day period, but these changes were not considered to be indicative of deleterious effects. Low concentrations of tungsten were detected in gonad and kidney samples from males and females and in liver samples from females dosed with tungsten-polymer shot. Tungsten was also detected in femur samples from tungsten-polymer-dosed mallards. Higher concentrations of tungsten were detected in femur, liver, kidney, and gonad samples from tungsten-iron-dosed ducks. Tungsten-iron or tungsten-polymer shot repeatedly administered to adult mallards did not cause adverse hematological effects during the 150 day trial. Concentrations of tungsten in the femur, liver, kidneys, and gonads were generally higher in tungsten-iron-dosed ducks when compared to tungsten-polymer-dosed ducks.

Chronic toxicity of dietary 2,3,7,8-tetrachlorodibenzo-p-dioxin to mink.

Mature female natural dark mink (Mustela vison) were fed 0.0006 (control), 0.016, 0.053, 0.180, or 1.40 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 131-132 d to ascertain the chronic toxic effects of TCDD in mink, including reproduction. Consumption of the 1.4 ppb TCDD diet resulted in lethargy, bloody stools, and 16.7% mortality. Final mink body weights were inversely proportional to the dietary TCDD concentrations. Due to subnormal mink breeding, definitive effects of TCDD on mink reproductive performance were not ascertained; however, there were significant dose-dependent decreases in kit (young mink) birth weight and survival from birth to 3 w of age in the groups that had reproduction. There were also significant differences in adult minkwhite blood cell counts, plasma total solids, serum iron, phosphorus, albumin, total protein, total CO2, cholesterol, osmolality, and anion gap concentrations, and alanine aminotransaminase activity between the various dietary groups. During the latter stages alopecia and thickened, deformed, and elongated toenails were observed in the adult mink fed 1.4 ppb TCDD. At termination the mink fed 1.4 ppb TCDD had ascites, gastric ulcers, intestinal hemorrhages, depletion of adipose tissue, and mottled and/or discolored livers, spleens, and kidneys. Focal lymphocytic meningitis in region of the olfactory bulb was present in 42% of the mink fed 1.4 ppb TCDD. These results confirmed the high sensitivity of mink to TCDD and revealed a toenail abnormality not previously reported for mink fed TCDD.

Dietary exposure to 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2,3,7,8-tetrachlorodibenzo-p-dixon (TCDD) does not induce proliferation of squamous epithelium or osteolysis in the jaws of weanling rats.

Previous studies demonstrated that dietary exposure to 24 ppb 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2.4 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induced maxillary and mandibular proliferation of periodontal squamous epithelium, osteolysis of alveolar bone, and loose and displaced teeth in juvenile mink (Mustela vison). This study determined if such effects could be induced in laboratory rats. Feeding weanling male Long Evans rats 20 or 100 ppb PCB 126 or 1 or 10 ppb TCDD for up to 101 days caused a dose-dependent decrease in body weight gains but did not produce the jaw lesion observed in PCB 126- or TCDD-treated mink.

Squamous epithelial proliferation in the jaws of mink fed diets containing 3,3',4,4',5-pentachlorobiphenyl (PCB 126) or 2,3,7,8-tetrachlorodibenzo-P-dioxin (TCDD).

Previous research has shown that ingestion of 3,3',4,4',5-pentachlorobiphenyl (PCB 126) by juvenile mink (kits) caused a lesion in the mandible and maxilla that consisted of proliferation of sQuamous epithelium in the periodontal ligament, osteolysis of adjacent alveolar bone, and loose and displaced teeth. Similar, but less severe changes, developed in adult mink fed 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The present study was conducted to compare similarities and differences of the lesion within the jaws of mink fed these 2 polyhalogenated hydrocarbons. Diets containing 24 ppb PCB 126 or 2.4 ppb TCDD were fed to 6-w-old kits for 36 d. Similar diets were fed to 12-w-old kits for 35 d. Some of these mink were then fed untreated feed for an additional 50 d. All mink treated with PCB 126 or TCDD had reductions in body weight gains which were more severe in the 6-w-old kits than the 12-week-old kits. By 28 days of exposure, many of the 6- and 12-week-old mink treated with PCB 126 or TCDD had loose and displaced incisor teeth. Canine teeth were grossly more prominant. Radiographs showed maxillary and mandibular osteolysis with lysis of the lamina dura in treated mink. Withdrawal of the toxicants from the diets of the 12-w-old mink failed to alleviate the lesions, which continued to be progressively more severe.

Proliferation of maxillary and mandibular periodontal squamous cells in mink fed 3,3',4,4',5-pentachlorobiphenyl (PCB 126).

This report characterizes squamous cell proliferation in young farm mink (Mustela vison) fed a diet supplemented with 0.024 ppm 3,3',4,4',5-pentachlorobiphenyl (polychlorinated biphenyl [PCB] congener 126). One to 2 months of dietary exposure to PCB 126 resulted in gross lesions of the upper and lower jaws consisting of mandibular and maxillary nodular proliferation of the gingiva and loose teeth. The maxilla and mandible of the PCB-treated mink were markedly porous because of loss of alveolar bone. Histologically, this osteoporosis was caused by proliferation of squamous cells that formed infiltrating cords. This report clearly documents the fact that the environmental contaminant PCB 126 can cause osteoinvasive squamous proliferation in young mink, although the dose used in the present study was 7 and 36 times higher than what is typically encountered in contaminated bird eggs and fish, respectively.

Proliferation of periodontal squamous epithelium in mink fed 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

The maxilla and mandible from 2 adult female mink fed 5.0 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 6 mo were grossly unremarkable, but histologically had nests of squamous epithelium within the periodontal ligament. There was osteolysis of the adjacent alveolar bone.

Effects of dark-rearing on triphenyl phosphate-induced neuropathy in the visual system of the developing European ferret (Mustela putorius furo).

Results of a previous study in our lab (Tanaka et al., 1994) suggested that the onset of susceptibility to the organophosphorus compound triphenyl phosphite (TPP) in the developing ferret visual system might be closely related to eye opening and the onset of light stimulation. In order to explore this idea further, TPP was administered to ferret kits that had been raised for varying periods of time in total darkness to assess whether a delay in the onset of light stimulation to the visual system might also result in a delay in its susceptibility to TPP. Ferret kits were raised from birth either in total darkness or in open-sided sheds exposed to ambient light, injected subcutaneously with TPP (888 mg/kg body weight) at 5.5, 7.5, 9.5, or 21.5 wk of age, euthanized, and perfused transcardially with a 10% formalin-saline solution 4 d after injection. Brains were sectioned parasagittally at a thickness of 40 microm and subsequently processed with the Fink-Heimer silver impregnation technique to reveal the presence of degenerating axons and terminals, and with cresyl violet stain to delineate nuclear boundaries and cell soma morphology. Comparisons among degeneration patterns present in light-reared and dark-reared kits at the four ages examined revealed that the time of onset, extent, and density of TPP-induced axonal and terminal degeneration seen in the lateral geniculate nucleus and primary visual cortex did not differ significantly between light- and dark-reared groups, with the possible exception of dark-reared kits exposed to TPP at 7.5 wk of age. In addition, neurons in the primary visual cortex showed shrinkage and increased packing densities in kits exposed to TPP in both light and dark environments, as well as in dark-reared non-injected kits. The results of this study indicate that dark-rearing does not delay the onset or lessen the severity of TPP-induced axonal and terminal degeneration in the developing visual system of the ferret. Data suggest that light activation and stimulation of the retino-geniculo-striatal visual pathway is not a necessary prerequisite for the onset of visual system susceptibility to the axonopathic effects of triphenyl phosphite.

Effects of formalin on bacterial growth in mink feed, feed consumption and reproductive performance of adult mink, and growth of mink kits.

Feed that is typically used on commercial mink ranches is an ideal environment for bacterial growth because of the raw animal by-products used as ingredients. Recently, formaldehyde was approved for use as an antimicrobial agent in poultry feed. Experiments in our laboratory were carried out to investigate the effects of incorporating different concentrations of formalin into the feed of mink on the growth of gram-negative and gram-positive bacteria. Feed containing 0, 550 or 1100 ppm formalin was kept refrigerated for up to 7 d and the number of colony forming units of gram-negative and gram-positive bacteria derived from the feed was determined each day. Colony forming units in the formalin-treated feed were significantly fewer than colony forming units in untreated feed. In the second trial, feed containing the same concentrations of formalin was maintained at 30 C for 24 h and cultured bacterial colonies were counted at 0, 12 or 24 h of feed incubation. Both concentrations of formalin were effective in significantly reducing the number of colony forming units. A feed consumption trial determined if mink (Mustela vison) preferred formalin-treated feed to non-treated feed kept refrigerated for up to 7 d. Consumption of feed treated with 1100 ppm formalin was significantly lower than consumption of the non-treated feed on d 1, 2, 4 and 5, but body weight was not affected. A long-term feeding trial determined the effects of formalin on mink reproduction, early growth of offspring and quality of fur. Mink were fed formalin at concentrations of 0, 550 or 1100 ppm for approximately 140 d beginning 1 mo prior to mating until kits were weaned at 6 w of age. Mating success was not affected by consumption of formalin-treated diets, but kit survival at birth was adversely affected in mink consuming 1100 ppm formalin. Hemoglobin concentration, hematocrit, mean corpuscular volume, and mean corpuscular hemoglobin were significantly decreased in 6-w-old kits, but there were no significant differences in any of these parameters between the kits exposed to 0 and 550 ppm formalin. In a second phase, some kits and their dams were continued on their respective dietary treatments from weaning through pelting (approximately 220 and 320 d, respectively). At pelting, hematocrits and hemoglobin concentrations for the kits fed 1100 ppm formalin were significantly less compared to the control and 550 ppm formalin groups. There were no significant differences in body weights among female kits or adult female mink. The body weights of male kits in the 1100 ppm formalin group became significantly less than the body weights of male kits in the control and 550 ppm formalin groups as the trial progressed. The quality of fur was highest for mink in the control group and lowest for mink in the 1100 ppm formalin group. While dietary 1100 and 550 ppm formalin were effective in suppressing bacterial growth in the feed of mink, the deleterious effects of 1100 ppm formalin on kit survival, hematologic parameters, body weight, and quality of fur preclude formalin use at this concentration.

Organophosphorus-induced neurotoxicity in the absence of neuropathy target esterase inhibition: the effects of triphenyl phosphine in the European ferret.

Abou-Donia et al. (in Toxicologist, Vol. 30, 1996) have reported that repeated oral administration of the organo-phosphorus compound triphenyl phosphine (TPPn) to the domestic chicken results in neuropathological changes in the spinal cord and peripheral nerves, accompanied by ataxia and paralysis. This study also noted that single doses of TPPn resulted in no inhibition of the enzymes neuropathy target esterase (NTE) and acetylcholinesterase (AChE). We undertook the present study to determine the biochemical, neuropathological, and clinical effects of single doses of TPPn in the European ferret, a mammalian species shown to be susceptible to organophosphorus-induced neurotoxicity. Eight 12-week-old ferrets were each injected subcutaneously with either 250 mg TPPn/kg bw or 500 mg TPPn/kg bw, or with the peanut oil/ethyl ether vehicle. Twenty-four h after dosing, the brains of 5 animals from each dose group were examined for NTE and AChE activities. The remaining 3 animals in each group were observed for 6 days for the development of clinical signs, after which their brains were processed for the presence of axonal degeneration using the Fink-Heimer silver impregnation method. Single injections of TPPn had no effect on the activities of whole-brain NTE or AChE 24 h after injection. The animals observed for clinical signs showed increasing trunk and hindlimb ataxia beginning 4 days after injection, culminating in fore-and hindlimb paralysis 6 days after injection. All brains exposed to either dose of TPPn showed widespread axonal degeneration extending from the brainstem and cerebellum into midbrain and forebrain areas. The results of this study support the hypothesis that TPPn-induced neurotoxicity is a separate and distinct form of organophosphorus-induced neurotoxicity not dependent on NTE inhibition, and therefore not a variant of organophosphorus-induced delayed neurotoxicity (OPIDN).

Toxic effects to mink of moniliformin extracted from Fusarium fujikuroi culture material.

Acute and subacute effects of i.p. exposure to moniliformin in mink (Mustela vison) were investigated. Moniliformin was extracted from Fusarium fujikuroi culture material containing 9,174 ppm moniliformin. An acute LD50 between 2.2 and 2.8 mg moniliformin/kg bw was determined for 9-mo-old female mink. Subacute exposure to 1.5 to 3.2 mg total moniliformin/kg bw resulted in dilated (right side) hearts rounded in appearance. Statistical differences observed in serum chloride and albumin, amylase activities, spun packed-cell volumes, red blood cell counts, hemoglobin concentrations, and hematocrit values between control and moniliformin-dosed mink were considered biologically insignificant because values were within ranges reported for normal mink. Electron microscopic examination of the right ventricular free heart wall of mink receiving acute or subacute doses of moniliformin revealed ultrastructural damage to myofibers, mitochondria, nuclei, Z- and M-lines and sarcoplasmic reticula, and increased extracellular collagen deposition. These results showed that mink are among the more sensitive mammals to moniliformin and that this mycotoxin specifically targets and damages the hearts of mink.

Acute effects of lead, steel, tungsten-iron, and tungsten-polymer shot administered to game-farm mallards.

Sixteen-bird groups (sexes equal) of adult mallards (Anas platyrhynchos) were orally dosed with eight #4 steel short, eight #4 lead shot, eight BB-size tungsten-iron shot, eight BB-size tungsten-polymer shot, or were sham-dosed and maintained for 30 days (16 January 1996 to 15 February 1996). Half of the lead-dosed ducks (five males, three females) died during the study, whereas no ducks died in the other dosage groups. For lead-dosed ducks, hematocrit and hemoglobin concentration were decreased on day 15 of the trial, but not on day 30. Delta aminolevulinic acid dehydratase activity in lead-dosed ducks was lower when compared to steel-dosed ducks only. Plasma activities of selected enzymes were elevated in lead-dosed ducks when compared to enzyme activities of ducks in the other groups. For lead-dosed ducks, relative heart, liver, and kidney weights increased in comparison to relative weights of those organs of ducks in other groups. Histology of tissues indicated that renal nephrosis accompanied by biliary stasis was present in the eight lead-dosed ducks that died. For the eight lead-dosed ducks that survived, six had mild to severe biliary stasis. Mild biliary stasis was noted in five tungsten-iron dosed ducks and three tungsten-polymer dosed ducks. Amounts of lead in the femur, liver, and kidneys were higher in lead-dosed ducks than in ducks of the other four groups. Small amounts of tungsten were detected in the femur and kidneys of two tungsten-polymer dosed ducks. Higher concentrations of tungsten were detected in the femur, liver, and kidneys of all tungsten-iron dosed ducks. The rate of shot erosion was highest (80%) for the tungsten-polymer shot, followed by tungsten-iron (55%), lead (50%), and steel shot (33%). Results indicated that tungsten-iron or tungsten-polymer shot (8 shot/duck) orally administered to mallards did not adversely affect them during a 30-day trial.

Subacute and reproductive effects in mink from exposure to Fusarium fujikuroi culture material (M-1214) containing known concentrations of moniliformin.

This study was conducted to ascertain the subacute and reproductive effects in mink (Mustela vison) resulting from exposure to moniliformin, a toxic mycotoxin produced by Fusarium fungi. In a preliminary trial, adult mink were presented diets that contained targeted concentrations of 10, 20, 40, 80, 160, or 240 ppm moniliformin provided by F. fujikuroi culture material (M-1214). The mink fed diets that contained more than 40 ppm moniliformin refused to eat significant quantities of feed. Feeding adult mink diets that contained 8.1 or 17.0 ppm (wet weight) moniliformin, provided by F. fujikuroi culture material, in a 30-day subacute trial produced no significant adverse effects on feed consumption, body weights, hematologic parameters, or serum chemical values, and notable histologic changes in tissues that were examined. In the reproduction trial, female mink were exposed to the same dietary concentrations of moniliformin provided by F. fujikuroi culture material as in the subacute test from 2 weeks prior to the breeding season until their offspring (kits) were 8 weeks old. Consumption of the high-dose (17 ppm) diet resulted in significant neonatal mortality and reduced kit body weights at birth and at 8 weeks of age. Necropsy of 8-week-old kits from the control and high-dose groups revealed no gross or histologic lesions or alterations in liver, lung, or heart tissues that could account for the mortality observed in the kits exposed to the culture material. These results indicate that long-term (105-135 days) dietary exposure to F. fujikuroi culture material containing 17 ppm moniliformin is not lethal to adult female mink, but can have adverse effects on neonatal mink.

Effects of dietary exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in adult female mink (Mustela vison).

Adult female mink were fed diets supplemented with 0, 0.001, 0.01, 0.1, 1, 10, or 100 ppb 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for up to 125 days. There was a dose-dependent decrease in feed consumption and body weights indicative of the "wasting syndrome" previously reported for mink and other species exposed to chlorinated hydrocarbon compounds. Mortality reached 12.5, 62.5, and 100% by day 28 in the 1-, 10-, and 100-ppb groups, respectively, and by day 125, mortality increased to 62.5 and 100% in the 1- and 10-ppb groups, respectively. Adrenal gland weights were significantly greater in the three highest dose groups compared to the control group. The percentage of band neutrophils was also significantly greater in the TCDD-treated groups compared to the control. LC50 (+/- SE) values for 28 and 125 days of dietary exposure to TCDD were calculated to be 4.8 +/- 4.99 ppb and 0.85 +/- 0.64 ppb, respectively. Based on feed consumption of control mink, these LC50 concentrations approximate 0.264 and 0.047 microgram TCDD/kg body weight/day for the 28- and 125-day exposure periods, respectively. These results confirm the sensitivity of mink to TCDD.

Multigenerational study of the effects of consumption of PCB-contaminated carp from Saginaw Bay, Lake Huron, on mink. 1. Effects on mink reproduction, kit growth and survival, and selected biological parameters.

This study was conducted to determine the multigenerational effects of consumption of PCB-contaminated carp (Cyprinus carpio) from Saginaw Bay (Lake Huron) on mink (Mustela vison) reproduction and health and to examine selected biomarkers as potential indicators of polyhalogenated hydrocarbon toxicity in mink. The mink were fed diets formulated to provide 0 (control), 0.25, 0.5, or 1.0 ppm polychlorinated biphenyls (PCBs) through substitution of Saginaw Bay carp for ocean fish in the diets. To determine whether the effects of PCB exposure were permanent, half of the parental (P1) animals were switched from their respective treatment diets to the control diet after whelping the first of two F1 generations. Effects of in utero and lactational exposure to PCBs on subsequent reproductive performance of the F1 animals were examined by switching half of the first-year F1 offspring (kits) to the control diet at weaning, while the other half was continued on their parental diet (continuous exposure). Continuous exposure to 0.25 ppm, or more, of PCBs delayed the onset of estrus (as determined by vulvar swelling and time of mating) and lessened the whelping rate. Litters whelped by females continually exposed to 0.5 ppm, or more, of PCBs had greater mortality and lesser body weights than controls. Continuous exposure to 1.0 ppm PCBs had a variable effect on serum T4 and T3 concentrations. Compared to the controls, there were significant differences in kidney, liver, brain, spleen, heart, and thyroid gland weights of the mink continually exposed to 1.0 ppm PCBs. There was an increase in the incidence of periportal and diffuse vacuolar hepatocellular lipidosis in the P1 mink with continuous exposure to increasing concentrations of PCBs. Plasma and liver PCB concentrations of the adult and kit mink were, in general, directly related to the dietary concentration of PCBs and the duration and time of exposure. Short-term parental exposure to PCBs had detrimental effects on survival of subsequent generations of mink conceived months after the parents were placed on "clean" feed. The lowest observed adverse effect level (LOAEL) for dietary PCBs in this study was 0.25 ppm.

Multigenerational study of the effects of consumption of PCB-contaminated carp from Saginaw Bay, Lake Huron, on mink. 2. Liver PCB concentration and induction of hepatic cytochrome P-450 activity as a potential biomarker for PCB exposure.

This study examined the effect of polychlorinated biphenyls (PCBs) from Saginaw Bay (Lake Huron) carp on the hepatic cytochrome P-450 activity in mink (Mustela vison). Hepatic cytochrome P-450 activities are of interest for their possible use as biomarkers to indicate consumption and biological effects of PCBs in the environment. Adult mink were fed diets containing ocean fish (control diet, 0.0 ppm) or Saginaw Bay carp toprovide 0.25, 0.5, or 1.0 ppm PCBs. Mink were bred after 3 mo of exposure, and half of the parental mink (P1) and kits (F1-1) previously consuming diets containing Saginaw Bay carp were switched to control diet at weaning of the F1-1 kits. P1 and F1-1 mink were then bred within their age and dietary groups after 15 mo of exposure, to produce the second-year F1 (F1-2) and F2 kits. Mink were killed when the new kits were weaned. Transfer of half the animals to the control diet examined whether the effects of the PCB-containing diet on hepatic cytochrome P-450 activity were permanent. Continual exposure to diets containing PCBs from Saginaw Bay carp induced cytochrome P-450 activity in a generally dose-dependent manner. Cytochrome P-450 activity was not different from untreated controls in animals switched to the control diet from the PCB-containing diet. The response of cytochrome P-4501A1 (EROD) activity in a dose-dependent manner and the lack of induction after transfer to noncontaminated diets suggest that this hepatic enzyme activity is a potential biomarker for current exposure to PCBs and other similar cytochrome P-450 inducers.