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Biomedical subjects

T F Collins

Publications and source records attributed to T F Collins.

At least 19 recordsLinked to original sources
PubMed1998

Effects of fumonisin B1 in pregnant rats.

Fumonisin B1 (FB1), the major mycotoxin from Fusarium moniliforme, has been implicated as a causative agent in several animal and human diseases. Despite animal toxicity studies and human epidemiological studies of FB1, knowledge of its reproductive effects is scarce. In this study, one of a series of proposed studies that will allow extrapolation to humans, pregnant rats were given oral doses of 0, 1.875, 3.75, 7.5 or 15 mg FB1/kg on gestation days 3 16. Caesarean sections were performed on day 17 or 20, and maternal condition, implantation efficiency, foetal viability and foetal development were measured. Dose-related decreases in overall feed consumption and body weight gain were seen, but only the feed consumption decrease at 15 mg/kg, and the decreased body weight gain at 15 mg/kg on days 0-17 were statistically significant. Foetal body weights at day 17 were similar in control and treated groups; but in day-20 foetuses, female weight and crown-rump length were significantly decreased at 15 mg/kg. FB1 was not teratogenic at the doses tested, and no dose-related effects were seen in either skeletal or soft-tissue development. In day-17 animals, maternal and foetal brain, liver and kidney tissues, and maternal serum were preserved to study the levels of sphinganine (Sa), sphingosine (So), and the Sa/So ratios. Dose-related increases were seen in Sa/So ratios in maternal livers, kidneys and serum. Sa/So ratios of maternal brains were not affected, nor were those of foetal kidneys, livers or brains.

Abnormalities, Drug-Induced↗
PubMed1997

Lack of embryotoxicity of fumonisin B1 in New Zealand white rabbits.

Fumonisin B1 (FB1) is one of a number of mycotoxins produced by fungi, especially Fusarium sp. As a contaminant of many maize-derived products, this toxin is associated with a variety of animal diseases, including esophageal cancer and possibly neural tube defects in humans. We have investigated the embryotoxic potential of this compound in New Zealand White rabbits. Animals were dosed by gavage daily on GD 3-19 with purified FB1 at 0.10, 0.50, or 1.00 mg/kg/day. Maternal lethality occurred at the 0.50 and 1.00 mg/kg/day doses. When examined on GD 29, there were no differences in maternal body weight, maternal weight gain, maternal organ weights, number of nonlive implantations, and number of malformations. Fetal weight was decreased at 0.50 and 1.00 mg/kg/day (13 and 16%, respectively); this was true for male and female pups. Fetal liver and kidney weights were also decreased at these doses. Analysis of embryonic sphinganine to sphingosine ratios demonstrated no differences between control and treated embryos on GD 20, although these ratios were increased in maternal urine, serum, and kidney when compared to control animals. These data suggest that FB1 did not cross the placenta and that the observed decreased fetal weight was probably the result of maternal toxicity, rather than any developmental toxicity produced by FB1.

Acyltransferases↗
PubMed1997

Testing the potential of sodium fluoride to affect spermatogenesis in the rat.

The potential of sodium fluoride (NaF) to affect spermatogenesis and endocrine function was assessed in P and F1 generation male rats. Male and female experimental rats received sodium fluoride in their drinking water at one of four concentrations (25, 100, 175, 250 ppm). P generation male and female rats were exposed to sodium fluoride in their drinking water for 10 wk and then males were mated to females within the same treatment groups. Reproductive tissues were collected from P generation male rats after approximately 14 wk of treatment. Pregnant females (P) were exposed to sodium fluoride via their drinking water through gestation and lactation. F1 generation weanling male rats remained within the same treatment groups as their parents. F1 generation male rats were exposed to sodium fluoride in their drinking water for 14 wk, at which time reproductive tissues were collected. Dose-related effects were not observed within the P and F1 treatment groups in testis weights, prostate/seminal vesicle weights, non-reproductive organ weights, testicular spermatid counts, sperm production per gram of testis per day, sperm production per gram of testis, LH, FSH or serum testosterone concentrations. Histological changes were not observed in testicular tissues from either the P or F1 generation. We conclude that prolonged exposure to sodium fluoride in drinking water at the doses administered in this study does not adversely affect spermatogenesis or endocrine function in the P and F1 generation male rats.

Animals↗
PubMed1996

Effect of intratesticular injection of sodium fluoride on spermatogenesis.

The potential of sodium fluoride to affect spermatogenesis in the rat was assessed by intratesticular injection. Experimental rats' left testis was injected with sodium fluoride (50, 175 and 250 ppm) in vehicle (0.9% physiological saline); control testes were injected with vehicle. The right testis served as a non-injected control. Testicular tissues collected 'at' and 'distal to' the injection site and from the non-injected control testes were evaluated microscopically 24 hr and 1, 2 and 3 wk post-injection. Testicular tissues obtained at and distal to the injection site in all fluoride-injected groups resembled tissues collected from corresponding areas in the controls. Seminiferous tubule damage observed in both the vehicle-injected control testes and the fluoride-injected testes but not in the non-injected testes was attributed to injection trauma. Polymorphonuclear leucocyte infiltration was observed 24 hr post injection only at the injection site in the vehicle- and fluoride-injected groups. Leydig cells were unaffected. Leucocyte infiltration with seminiferous tubule damage was not considered to be a fluoride treatment-related effect because it was observed in both vehicle- and fluoride-injected testes. The results demonstrate that the rat is not adversely affected by direct exposure to fluoride at levels 200 times greater than those under normal conditions.

Animals↗
PubMed1995

Developmental toxicity of sodium fluoride in rats.

Despite the chronic exposure of the US population to fluoridated drinking water since the 1940s, existing studies have been judged inadequate to determine any potential reproductive or developmental hazard. This study was conducted to determine the effects of sodium fluoride (NaF) on foetal development. Sperm-positive female rats were given 0, 10, 25, 100, 175 or 250 ppm NaF daily throughout gestation. They were dosed by drinking water to mimic human exposure to fluoridated water. No dose-related behavioural changes or maternal clinical signs were noted. Fluid consumption by females in the 175- and 250-ppm groups was significantly less than that of the control females. Because of this decreased fluid consumption, the daily amount of NaF ingested (0, 1.4, 3.9, 15.6, 24.7 and 25.1 mg/kg body weight) was less than expected at the two high levels. Feed consumption decreased significantly at 250 ppm, and body weights of pregnant females reflected feed consumption trends. The mean number of viable foetuses per female in all treated groups was similar to that of the control group. The significant decrease in the mean number of implants per litter in the 250-ppm group is probably linked to the lower mean number of corpora lutea in this group. The occurrence of in utero deaths was similar in the control and treated groups. Foetal growth (in terms of foetal body weight and crown-rump length) was not affected by NaF, despite the fact that the dams in the 250-ppm group ate significantly less feed and drank significantly less fluid. There was no dose-related increase in the number of external anomalies in foetuses due to NaF ingestion. At the doses given, NaF had no effect on the development of specific bones, including sternebrae. A significant increase was seen in the average number of foetuses with three or more skeletal variations in the 250-ppm group; the number of litters with foetuses with three or more skeletal variations was increased in the 250-ppm group also, but the increase was not significant. There was no dose-related effect of NaF on the incidence of soft tissue variations.

Abnormalities, Drug-Induced↗
PubMed1994

Developmental effects of combined exposure to ethanol and vitamin A.

The potential for ethanol (EtOH) to influence the developmental toxicity of vitamin A was investigated. 11 groups of approximately 31 FDA-bred Osborne-Mendel rats received either a control or isocaloric 6.4% EtOH liquid diet (containing 4000 IU vitamin A/litre) ad lib. The vehicle control, EtOH and pair-fed (pair-fed against the EtOH group) groups received corn oil (the vehicle) by gavage. Vitamin A was administered by gavage without EtOH at 40,000, 80,000, 120,000 or 160,000 IU/kg daily. Vitamin A was administered by gavage at 10,000, 20,000, 40,000 or 80,000 IU/kg with EtOH ad lib., daily throughout the study. Combined EtOH and vitamin A resulted in significant reductions in maternal diet consumption and body weight when doses of vitamin A were as low as 10,000 IU/kg. The most severe effects on overall (days 0-20) maternal body weight gain were observed in the groups receiving 120,000 or 160,000 IU vitamin A/kg alone or EtOH in combination with 80,000 IU vitamin A/kg. The overall diet consumption (days 0-20) paralleled the overall weight gain. In general, pups exposed to ethanol and vitamin A had a tendency to weigh less than those exposed to vitamin A alone, but to weigh more than those exposed to EtOH alone. EtOH combined with vitamin A at 80,000 IU/kg resulted in an increased incidence of cleft palate relative to the vehicle control or either treatment alone. The incidence of exencephaly and protruding tongue was significantly greater in the group given vitamin A at 160,000 IU/kg, compared with the vehicle control group. The most consistent statistically significant skeletal finding in the groups receiving combined treatment was a treatment-related increased incidence of supernumerary ribs [14th rib (C7), 14th rib bud (L1) and 15 ribs]. In addition, the incidence of misshapen zygomatic arch was also significantly increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg. The incidence of moderately enlarged renal pelvis and severely enlarged ureter proximal to the kidney was increased in the group exposed to EtOH and vitamin A at 80,000 IU/kg relative to the vehicle control, or either treatment alone. Therefore, for some of the endpoints examined in this investigation, it would appear that ethanol potentiates the developmental effects of vitamin A.

Abnormalities, Drug-Induced↗
PubMed1994

Effect of ethanol and vitamin A excess on vitamin A status in the liver, plasma and foetuses of pregnant rats.

The effect of maternal consumption of dietary ethanol and high doses of vitamin A by gavage was investigated by evaluating plasma, liver and foetal vitamin A in Osborne-Mendel pregnant rats with a view to assessing whether ethanol modulated the potential toxicity of excess vitamin A. All groups received 4000 IU vitamin A/litre in a liquid diet. Ethanol-exposed groups also received 6.4% (v/v) ethanol in the liquid diet. Vitamin A was administered by gavage once per day in corn oil in doses ranging from 10,000 to 160,000 IU/kg body weight. Plasma vitamin A levels in ethanol-exposed groups were similar to levels in a pair-fed group. Plasma vitamin A levels were similar in the group given ethanol plus 40,000 IU vitamin A/kg and the group given 40,000 IU vitamin A/kg only, but were higher in the group receiving ethanol plus 80,000 IU vitamin A/kg than in the group given 80,000 IU vitamin A/kg only. Retinyl esters were present in the plasma of animals receiving 160,000 IU vitamin A/kg only, indicating possible saturation of the liver with vitamin A. Retinyl palmitate levels in female foetuses of the group administered ethanol plus 80,000 IU vitamin A/kg were significantly higher than those of the group administered 80,000 IU vitamin A/kg only; no significant differences in levels of retinyl palmitate in male foetuses were observed between these two groups. This observation suggests a possible sex difference in the modulation of vitamin A toxicity by ethanol in the foetus.

Administration, Oral↗
PubMed1994

Mineral interactions in rats fed AIN-76A diets with excess calcium.

The effects of moderate increases in dietary calcium on maternal and foetal mineral interactions were studied in Charles River CD/VAF Plus rats. Female rats were given 0.50, 0.75, 1.00 or 1.25% dietary calcium as calcium carbonate in AIN-76A diets for 6 wk before mating, during mating and for 20 days of gestation. Inductively coupled argon plasma-atomic emission spectrometry was used to determine mineral levels in the tissues of non-pregnant rats after 42 days on the diets, in the tissues of pregnant rats on day 20 of gestation and in the whole body of day-20 foetuses. The femurs of the non-pregnant and pregnant rats had a dose-related linear increase in calcium content. In livers of the non-pregnant rats, dose-related linear increases in the phosphorus, zinc and magnesium content were observed, but there was a dose-related decrease in the iron content. There were dose-related linear decreases in the iron and copper contents of the kidneys from the non-pregnant rats. In pregnant rats dose-related linear decreases were observed in the iron content of the liver and in the zinc, iron and magnesium contents of the kidney. The foetuses from rats given a moderate increase in dietary calcium had dose-related decreases in the whole-body contents of phosphorus, iron, copper and magnesium.

Animals↗
PubMed1993

Foetal development in rats fed AIN-76A diets supplemented with excess calcium.

This study was designed to evaluate the developmental effects of moderate dietary calcium increases in rats fed nutritionally adequate diets. Female Charles River CD/VAF Plus rats were given 0.50 (control), 0.75, 1.00 or 1.25% dietary calcium as calcium carbonate in AIN-76A diets for 6 wk before mating, during mating and for 20 days of gestation. On gestation day 20, the animals were killed and caesarean sections were performed. Both the non-pregnant and pregnant rats in the 0.75, 1.00 and 1.25% groups ate slightly more than did the control group during most of the intervals measured, but not all the increases were statistically significant. There was no consistent pattern of increase or decrease in weight gain. No dose-related changes were found in maternal clinical findings, the average number of implantations, resorptions and viable foetuses, or foetal length or weight. Under the conditions of the study, there were no statistically significant increases as compared with the control group in the litter incidence regarding specific external, visceral or skeletal variations of the foetuses. Dietary calcium was neither foetotoxic nor teratogenic at the concentrations used.

Analysis of Variance↗
PubMed1993

Teratogenic potential of FD & C red no. 3 when given in drinking water.

FD & C Red No. 3 (erythrosine), a commonly used food additive, was administered to pregnant Osborne-Mendel rats to study its teratogenic potential. Dosing solutions of 0.05, 0.1, 0.2 or 0.4% in distilled water were available at all times and corresponded to daily doses of 64, 121, 248 and 472 mg FD & C Red No. 3/kg body weight. Distilled water served as the control. On gestation day 20, the animals were killed and caesarean sections were performed. The treated animals consumed less fluid than did the control animals, but only random decreases were statistically significant and no dose relationship was seen. Only the 0.2% group consumed significantly more feed than the controls during gestation. Maternal weight gain during days 0-20 was not significantly affected in any group. No dose-related changes were seen in maternal clinical findings, implantations, foetal viability, foetal size (weight and length) or visceral development. No dose-related teratogenesis was seen. Skeletal development was not affected; the few statistically significant increases in skeletal variations were not dose related and were considered to be random. FD & C Red No. 3 was neither foetotoxic nor teratogenic at the dose levels tested in drinking water.

Administration, Oral↗
PubMed1992

Study of the teratogenic potential of FD & C yellow No. 5 when given in drinking-water.

FD & C Yellow No. 5 was available to pregnant Osborne-Mendel rats throughout gestation at dose levels of 0.05, 0.1, 0.2, 0.4 or 0.7% in solution in distilled drinking-water. Based on fluid consumption, the rats received 67.4, 131.8, 292.4, 567.9 and 1064.3 mg FD & C Yellow No. 5/kg body weight/day. Distilled water served as the control. No dose-related changes were seen in mean daily food consumption or maternal body-weight gain. Starting during the second trimester of gestation, fluid consumption was significantly greater in the rats given 0.7% FD & C Yellow No. 5 than in the controls. The females were killed on gestation day 20. No dose-related changes were seen in maternal clinical findings, implantations, foetal viability or foetal size (weight and length). No dose-related foetal terata were seen. Neither visceral development nor skeletal development (sternebral and other skeletal bones) was affected by the dye. The small numbers of statistically significant increases in skeletal variations in the 0.05 and 0.4% levels are considered random because they are not dose related.

Abnormalities, Drug-Induced↗
PubMed1990

Developmental effects and mineral interactions in rats fed textured vegetable protein.

The teratogenic effects of feeding a diet based on textured vegetable protein to Long-Evans rats were studied along with maternal and fetal mineral interactions and their relationship to diet composition. Pregnant rats were fed purified diets containing 18% protein as casein (CAS), textured vegetable protein (TVP, from defatted soy flour) with 18 mg Zn/kg, or TVP diet with 100 mg Zn/kg. A fourth group was fed diet NIH-31. The animals received their diets throughout pregnancy and were sacrificed on day 20 of gestation. Fetuses were examined for developmental effects, and mineral levels were determined in maternal and fetal tissues by inductively coupled argon plasma-atomic emission spectrometry. Females fed the casein diet or diet NIH-31 had normal weight gains throughout pregnancy and their progeny exhibited normal development. The animals on the TVP-containing diet with 18 mg Zn/kg had decreased food consumption and body weights, and their fetuses exhibited developmental anomalies as well as reductions in size and weight. These developmental alterations may be the result of decreased zinc levels in the fetal tissues, caused by reduced bioavailability of the trace element in the maternal diet. Significant increases in tissue iron accompanied the low zinc levels. No developmental effects were found in animals receiving the high Zn-TVP diet, and mineral data from these animals were not significantly different from the casein group.

Animals↗
PubMed1990

Study of the teratogenic potential of FD & C Yellow No. 5 when given by gavage to rats.

FD & C Yellow No. 5 (tartrazine) was given to Osborne-Mendel rats by gavage at dose levels of 0, 60, 100, 200, 400, 600 or 1000 mg/kg body weight/day on days 0-19 of gestation. No maternal or developmental toxicity was observed when the rats were killed on day 20. The mean daily food consumption for the entire period of gestation was significantly greater in the females given 1000 mg/kg body weight/day than in the controls, but maternal body-weight gain was not affected. No dose-related effects were observed in implantations, foetal viability or external foetal development. Foetal skeletal and visceral development was similar among foetuses from all groups. At the doses given, FD & C Yellow No. 5 was neither toxic nor teratogenic.

Abnormalities, Drug-Induced↗