PubMed Health⌕ Search

Biomedical subjects

R E Butcher

Publications and source records attributed to R E Butcher.

At least 19 recordsLinked to original sources
PubMed1984

Behavioral and physical development of rats chronically exposed to caffeinated fluids.

Coffee and caffeine solutions were administered as the sole source of fluid to male and female Sprague-Dawley rats (F0) beginning 60 days before breeding and continuing until the litters (F1) from these animals were weaned. Treatments were administered as 100% brewed coffee (COF-100), and a 25% dilution of coffee (COF-25), together with solutions of caffeine in water that paralleled the caffeine content of the coffee groups, 0.056% caffeine (CAF-100) and 0.014% (CAF-25). Controls received measured amounts of plain water (CNL) and another group received vitamin A (40,000 IU/kg) on Days 7-20 of gestation (positive control treatment). During pregnancy all groups receiving COF and CAF consumed significantly more fluid than CNLs. Offspring from the COF-100 and CAF-100 dams were significantly lower in weight than CNLs. No abnormalities of reproductive performance were observed. Of 10 preweaning tests, COF-100 and CAF-100 litters displayed delayed incisor eruption, delayed swimming development, and altered activity. On 7 postweaning measures, these groups showed decreased running wheel activity and increased open-field ambulation and/or defecation. The CAF-25 group, by contrast, showed an increase in running wheel activity. Vitamin A (Vit-A) offspring showed multiple effects, including delayed incisor eruption, increased pre- and postweaning open-field activity, and reduced running wheel activity. COF and CAF produced effects on tests for psychoteratogenesis that appear consistent with the morphological consequences (delayed development) known to be associated with pre- and neonatal administration of caffeine, alone or in coffee, at high doses. The data indicate that most of the behavioral effects observed from caffeine exposure were consistent with the expected effects of concurrent administration of this agent, while the postweaning exposure effects suggest a longer-term change in activity. No effects of caffeine were found, however, on measures of learning, memory, or motoric functioning.

Animals↗
PubMed1984

Developmental toxicity and psychotoxicity of sodium nitrite in rats.

Sodium nitrite (NaNO2) was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through day 90, at levels of 0, 0.0125, 0.025 or 0.05% (w/w) of the diet. Dams in a fifth group (positive controls) were given 4 mg/kg ip of the anti-mitotic/embryotoxic drug 5-azacytidine on day 16 of gestation. All offspring were reared by their natural dams and were evaluated blind with respect to treatment in a battery of standardized behavioural tests between 3 and 90 days of age. NaNO2 produced no significant reductions in parental body weight or food consumption, though it significantly increased offspring mortality and decreased weight gain at the two highest doses during the preweaning period. Functionally, NaNO2 delayed swimming development and decreased open-field activity. The open-field effect was not linearly dose dependent. In rats killed on day 90 after birth, NaNO2 produced no effects on brain or body weights. 5-Azacytidine produced evidence of substantially greater developmental toxicity than did NaNO2. NaNO2 produced a moderate degree of developmental toxicity, but no evidence was found to suggest that the central nervous system was the target organ for the toxic effects. The inclusion of tests of functional development added useful confirmatory evidence to the overall picture of NaNO2 toxicity.

Aging↗
PubMed1984

Developmental toxicity and psychotoxicity of potassium iodide in rats: a case for the inclusion of behaviour in toxicological assessment.

Potassium iodide (KI) was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. Dams in a fifth group (positive controls) were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation. All offspring were reared by their natural dams and were evaluated blind with respect to treatment in a battery of standardized behavioural tests between 3 and 90 days of age. KI produced no significant reductions in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality at the highest dose, and decreased weight gain at the two highest doses throughout the first 90 days after birth. Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels. In rats killed on day 90 after birth KI reduced brain and body weight at a dose of 0.1% of the diet, and reduced body but not brain weight at a dose of 0.05% of the diet. No significant effect was found on absolute or relative thyroid weight at 90 days of age. Several additional behavioural effects were observed in the low-dose KI group, but because these effects were not dose-dependent, they were not regarded as reliable. 5-Azacytidine produced evidence of substantially greater developmental toxicity than KI. It was concluded that KI produced evidence of developmental toxicity consistent with a picture of impaired thyroid function. The inclusion of tests of functional development added useful evidence to the overall picture of KI developmental toxicity.

Administration, Oral↗
PubMed1983

Behavioral and reproductive effects of chronic developmental exposure to brominated vegetable oil in rats.

Adult Sprague-Dawley rats were fed diets containing 0, 0.25, 0.5, 1.0, or 2.0% of the food additive brominated vegetable (soybean) oil (BVO) for 2 weeks prior to mating. After conception, the diets were continued throughout gestation and lactation for the females. The same diets were also provided to the dams' offspring throughout their development (up to 90-120 days of age). BVO at 2.0% of the diet completely blocked reproduction. BVO at 1.0% of the diet severely impaired conception, reduced maternal body weight, and produced slightly reduced litter sizes but no evidence of malformations. At this dose postnatal mortality was high, and survivors showed impaired growth and severe behavioral impairments on a battery of standardized tests of functional development. After weaning, adequate data could not be obtained because of the high mortality rate in this group. BVO at 0.5% of the diet produced less reproductive interference and much less offspring mortality or impairment of growth, but produced behavioral impairments almost as severe as seen in the BVO 1.0% group. In addition, this group exhibited severely reduced postweaning activity, delayed vaginal patency development, and reduced day-90 weight. BVO at 0.25% of the diet produced reproductive deficits similar to the BVO 0.5% group, but less severe effects on growth and behavioral development. This group showed no significant increase in offspring mortality. The data demonstrate clear evidence of dose-related physical and behavioral developmental toxicity.

Animals↗
PubMed1983

A developmental toxicity and psychotoxicity evaluation of FD and C red dye #3 (erythrosine) in rats.

Two experiments were conducted to evaluate FD and C Red Dye #3 for its developmental toxicity and psychotoxicity. Adult Sprague-Dawley rats were fed diets containing the dye for 2 weeks and were then bred. The diets were continued for the females throughout gestation and lactation and were provided continuously to their offspring thereafter. The treatment groups for Experiment 1 were Red Dye #3 as 0.0, 0.25, 0.5, or 1.0% of the diet (w/w), and a positive control group treated with the toxin hydroxyurea on days 2-10 of life (50 mg/kg/day, s.c.); Experiment 2 was a replication of Experiment 1 with the same dose groups, but without the positive control group. Parental animals were evaluated for weight and food consumption, and females for reproductive success. The offspring were assessed on a series of tests using the Cincinnati Psychoteratogenicity Screening Test Battery, plus weight, food consumption, physical landmarks of development, and brain weight. Red-3 produced no reductions in parental or offspring weight or food consumption. Red-3 significantly increased preweaning offspring mortality in the first experiment, but not in the second. Behaviorally, Red-3 produced no dose-dependent effects that replicated across the two experiments. It was concluded that no evidence was obtained that dietary exposure to FD and C Red Dye #3 (erythrosine) is psychotoxic to developing rats.

Animals↗
PubMed1983

Developmental toxicity and psychotoxicity of FD and C red dye No. 40 (allura red AC) in rats.

Adult Sprague-Dawley rats were fed diets containing FD and C red dye No. 40 for 2 weeks and were then bred. The diets were continued for the females throughout gestation and lactation and were provided continuously to their offspring thereafter. The treatment groups were: FD and C red dye No. 40 as 0.0, 2.5, 5.0 or 10.0% of the diet, and a positive control group treated with the toxin hydroxyurea on days 2-10 of life with 50 mg/kg/day given s.c. as a positive control group. Parental animals were evaluated for weight and food consumption, and females for reproductive success. The offspring were assessed on a series of tests using the Cincinnati Psychoteratogenicity Screening Test Battery. Additional measures were weight, food consumption, physical landmarks of development, and brain weight. Red-40 significantly reduced reproductive success, parental and offspring weight, brain weight, survival, and female vaginal patency development. Behaviorally, R40 produced substantially decreased running wheel activity, and slightly increased postweaning open-field rearing activity. Overall, R40 produced evidence of both physical and behavioral toxicity in developing rats at doses of up to 10% of the diet.

Animals↗
PubMed1981

Progress in experimental phenylketonuria: a critical review.

Experimental progress in the development of an accurate and useful model of phenylketonuria (PKU) during the last 15 years is reviewed in detail. From this review it is clear that the recent emergence of models using the combined administration of phenylalanine (phe) and p-chlorophenylalanine (PCPA) constitutes a major success that lays the groundwork for future research into the pathogenesis and treatment of PKU. Biochemical evidence on the pathophysiology of PKU is also briefly reviewed in the context of the behavioral and biochemical adequacy of the models used. It appears that in the past biochemical investigations into PKU have been impaired by use of inadequate models, a situation that should now change if the best of the phe-PCPA models are more widely adopted. New trends in PKU research involve the role of large neutral amino acids other than phe as potential aids in the treatment of PKU and the appearance of a new model based on the use of alpha-methylphenylalanine (AMPhe) combined with phe. It appears that PKU research may be on the brink of a new and productive era as investigations into these promising areas unfold and as new emerge through the full utilization of existing models.

Abnormalities, Multiple↗
PubMed1981

Developmental neurobehavioral toxicity of butylated hydroxyanisole (BHA) in rats.

Butylated hydroxyanisole (BHA) was fed to rats throughout development (from prior to conception through 90 days of postnatal age) in doses of 0, 0.125, 0.25 or 0.5 percent (w/w) of the diet. A fifth group was also prepared as a positive control by administering 50 mg/kg/day of the antimitotic agent hydroxyurea on days 2-10 of postnatal age. Offspring from all groups were reared by their natural dams and were evaluated blind with respect to treatment assignment in a battery of standardized behavioral tests between 3 and 90 days of age. BHA at 0.5% of the diet impaired offspring growth during the last week of preweaning development and increased preweaning mortality (13.5%). No changes in maternal weight, reproductive performance or mortality were observed. No reductions in offspring growth after weaning or changes in day 90 brain weights were found. BHA at 0.25 and 0.125% of the diet had no effect on growth, reproduction or mortality; although a marginal increase was seen in the 0.25% BHA offspring mortality up to 30 days of age (8.3%, p = 0.06). BHA at 0.5 and 0.25% of the diet delayed startle development and showed a marginal trend towards increased diurnal running wheel activity; no other behavioral effects were found. Comparison of the present results to a similar study using BHT clearly indicates that BHA at equivalent dietary doses is considerably less toxic than BHT. The present results also suggest that BHA is not a potent behavioral toxin, although it is developmentally toxic using non-behavioral measures.

Aging↗
PubMed1980

Standards in behavioral teratology testing: test variability and sensitivity.

Regulatory guidelines have produced a need to develop behavioral screening techniques to accompany teratology and reproduction testing. In the repeated use of a provisional test battery, we have found that conclusions about the behavioral teratogenic potential of test compounds are most likely to be revealed using tests having intermediate levels of variability. The results obtained from examining animals exposed developmentally to brominated vegetable oil (BVO as 2.0, 1.0, 0.5, or 0.25 percent of the diet) and comparisons of the tests' coefficients of variation, offer an empirical example of this concept. Preweaning tests of locomotion and reflex development demonstrated numerous instances of developmental delay in the BVO-treated subjects, but postweaning tests revealed few abnormalities. Behavioral testing revealed functional deficits from BVO administration at doses lower than those which have adverse effects on reproduction. Examination of the tests' variability by using coefficients of variation as a comparative index, disclosed that the postweaning test variability was almost twice that of the preweaning tests. Thus, the lack of effects of BVO on most of the postweaning tests should not be conclusively interpreted as indicative of recovery of function, because this pattern is equally likely to have resulted from the lower sensitivity of these tests. An acceptable standard for future behavioral teratology screening requires a close examination of test variability, as it appears to be an important element in the sensitivity and, hence, the interpretation of such procedures.

Animals↗
PubMed1979

Psychotropic drugs as behavioral teratogens.

Three psychotropic drugs were administered to pregnant rats and were then evaluated for their behavioral and reproductive effects in the offspring. Control rats received either saline or vitamin A. Prochlorperazine had the most disruptive effects on reproduction and growth, but had the least effect on behavior. Propoxyphene had no apparent effects on reproduction or growth, but produced a variety of behavioral changes. Fenfluramine was intermediate in its effects on reproduction and growth and had behavioral effects that were revealed in tests of preweaning development. The data suggest that systematic tests of behavior add important information to evaluations of reproductive toxicity that cannot, at present, be obtained by other means.

Animals↗
PubMed1979

A preliminary test battery for the investigation of the behavioral teratology of selected psychotropic drugs.

Pregnant Sprague-Dawley rats received 25 mg/kg of prochlorperazine, 20 mg/kg of fenfluramine, 75 mg/kg of propoxyphene or 200 mg/kg of diazepam daily between the 7th and 20th days of gestation. Vehicle control groups and a positive control group (vitamin A 40,000 IU/kg/day) were similarly prepared. Observations of reproductive performance were made and the offspring examined in a battery of neurobehavioral tests. Fenfluramine and prochlorperazine produced abnormalities in both the reproductive measures and neurobehavioral testing. Propoxyphene produced developmental delays and other signs of "pure" behavioral teratogenesis in that these effects were not anticipated in any of the observations of reproductive performance. Diazepam appeared to have the mildest effect on all the measurements taken. The test methods used in this study appear to be a reasonable initial approach to the development of neurobehavioral screening procedures which are comprehensive, sensitive, and usable.

Animals↗
PubMed1979

Interlaboratory comparison of behavioral testing.

New requirements by several regulatory agencies for testing the psychotoxic potential of new drugs, chemicals, and environmental contaminants raise unique problems. In order to assess intra- and interlaboratory reliability of behavioral tests a model animal maze learning procedure was designed and run in 3 cooperating laboratories. Uniform procedures were written and identical mazes were constructed. Normal control animals of identical age and sex, but of different strains, were used by the participants. A positive control group of neurologically impaired rats was run by one laboratory. Significant differences in test results among the laboratories were found. Data obtained from the positive control animals (mean errors=28.3) indicated a learning impairment statistically significant compared to the negative control data (mean errors=12.7) from any of the participating laboratories. Based on the results of this study, a reasonable standard of interlaboratory reliability in behavioral testing appears an attainable goal.

Animals↗
PubMed1978

The relationship of gestational age to vitamin A induced postnatal dysfunction.

In an effort to determine the relationship between time of administration and consequent behavioral effects on progeny, a uniform subteratogenic dose of vitamin A (80,000 I.U./KG) was administered to gravid Sprague-Dawley rats during one of five periods of gestation (days 5-7, 8-10, 11-13, 14-16 and 17-19). Offspring were examined for changes in rate of weight gain, locomotor activity and maze learning ability (T-maze with return to nest as reward and multiple T water maze escape). Vitamin A 8-10 animals were hyperactive, vitamin A 11-13 animals acquired T-maze slower than controls and both vitamin A 8-10 and 11-13 acquired water maze slower than controls. Vitamin A 11-13 animals were significnatly lighter than controls and all other vitamin A groups.

Animals↗