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Biomedical subjects

B K Nelson

Publications and source records attributed to B K Nelson.

66 records · Page 4Linked to original sources
PubMedDate not supplied

Adult versus developmental neurotoxicology: an occupational perspective of similarities and differences.

Most readers of this journal are involved in neurotoxicology research, whether it is in adult or developing organisms. Although there are a number of similarities between adult and developmental neurotoxicology, there are also a number of differences. The intent of this "perspective" is to highlight some of the similarities and differences between these disciplines in the hopes of enhancing communication among neurotoxicologists.

Animals↗
PubMedDate not supplied

Utility of a single beta HCG measurement to evaluate for absence of ectopic pregnancy.

The objectives of this study were to determine the optimal cutoff value (CV) and utility of a single serum beta human chorionic gonadotropin hormone (HCG) level in assessing the likelihood of ectopic pregnancy (ECP). A retrospective chart review was performed at an urban county hospital. The optimal CV was determined by comparing all available patients diagnosed with ECP and patients diagnosed with threatened abortion (TA) in the Emergency Department (ED) who subsequently delivered a baby at the same hospital. The utility of the test was assessed in a group of all known patients who presented to the ED with lower abdominal or pelvic pain or vaginal bleeding between 6 and 13 weeks estimated gestational age (EGA). There were 212 ECPs with measured HCGs. Only nine presented after 13 weeks EGA. The mean HCG value was 5,378 mIU/mL. There was no significant correlation between HCG and EGA. There were 132 TAs with measured HCGs who subsequently delivered. Only four TAs presented before 6 weeks EGA. Regarding the TA patients who presented between 6 and 13 weeks EGA, there were 81 with a mean HCG of 83,810 mIU/mL. Between 6 and 13 weeks EGA, HCG was not significantly correlated with EGA. The entire ECP group was compared with the TA group with 6-13 week EGA. A receiver-operating characteristic curve with nine HCG cutoff values was constructed. Clinically, the optimal CV was 40K. At this level, a test for the condition "absence of ECP" had a specificity of 99%, and only two of 212 ECPs in our group would test false-positive with an HCG value over 40K. When the test was applied to a group of 175 women who presented with pain or bleeding between 6 and 13 weeks EGA, the sensitivity and positive predictive value for an intrauterine pregnancy were 24% and 99.9 %, respectively. However, if this test was applied to all patients regardless of clinical findings, and then an ultrasound (U/S) algorithm was applied to the patients who had an HCG of less than 40K, it would predictably increase the rate of ECPs falsely identified as intrauterine pregnancies (IUPs) by 1%, regardless of the false-positive rate of the U/S algorithm itself. Given the potential morbidity and mortality of undiagnosed ectopic pregnancy, ultimately neither this test nor any other that is less than 100% specific for IUP can be recommended instead of an initial U/S evaluation for patients who present at risk for ECP.

Biomarkers↗
PubMedDate not supplied

Developmental toxicity interactions of salicylic acid and radiofrequency radiation or 2-methoxyethanol in rats.

Radiofrequency (RF) radiation is used in a variety of workplaces where workers are concurrently exposed to chemicals. Combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The purpose of the present research was to determine if the synergistic effects noted for RF radiation and 2ME are generalizable to other chemicals. Since salicylic acid (SA) is widely used as an analgesic and is teratogenic in animals, SA was selected to address generalizability. Based on the literature and our pilot studies, 0, 250, or 350 mg/kg SA were administered by gavage on gestation Day 9 or 13 to rats. Concurrently rats given SA on Day 9 were exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 min (or sham). Those given SA on Day 13 were also given 0 or 100 mg/kg 2ME (gavage). Dams were sacrificed on gestation Day 20, and the fetuses were examined for external malformations. The data provide no evidence of synergistic interactions between RF radiation and salicylic acid (resorptions and malformations). Limited evidence of antagonism was observed between 2ME and salicylic acid (fetal weights). This investigation highlights the importance of additional research on interactions in developmental toxicology, and emphasizes the need to consider combined exposure effects when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Review of experimental male-mediated behavioral and neurochemical disorders.

Paternal exposures to exogenous agents have been reported to produce a variety of developmental defects in the offspring. In experimental animals, these effects include decreased litter size and weight, increased stillbirth and neonatal death, birth defects, tumors, and functional/behavioral abnormalities-some of these effects being transmitted to the second and third generations. This article reviews the exogenous agents that have reportedly caused behavioral or neurochemical alterations in offspring of experimental animals following paternal exposures, including advanced age, alcohols, cyclophosphamide, ethylene dibromide, lead, opiates, and a few miscellaneous chemicals. Based upon the consistency of effects in several of these agents in a variety of studies in experimental animals, the conclusion is that paternal exposures may contribute to the incidence of neurobehavioral disorders in humans.

Age Factors↗
PubMedDate not supplied

Paternal exposure of rabbits to lead: behavioral deficits in offspring.

Paternal exposures to exogenous agents have been reported to produce a variety of developmental defects in the offspring. In experimental animals, these effects include decreased litter size and weight, increased stillbirth and neonatal death, birth defects, tumors, and functional/behavioral abnormalities-some of these effects being transmitted to the second and third generations. The majority of experimental studies assessing nervous system function of offspring following paternal exposures have utilized rats as the experimental animal, but other species can be used. The National Toxicology Program (NTP) has initiated studies to validate the rabbit as an animal model for human reproductive toxicity, because rabbits are the smallest laboratory animal from which ejaculates can be collected repeatedly. An important part of reproductive toxicology is assessment of the reproductive ability of males following exposure, as well as developmental and functional assessment of their offspring. This article describes a pilot study and a main study to investigate the feasibility of using rabbits to assess the functional effects of paternal exposure to lead. The pilot study included seven male rabbits per group exposed for 15 weeks to lead acetate sufficient to produce 0, 50, or 110 micrograms/dl blood lead. The main study included 15 male rabbits per group exposed for 15 weeks to lead acetate to produce 0, 20, 40, and 80 micrograms/dl blood lead. At the conclusion of the exposure, male rabbits were mated with unexposed females. These females carried their litters to term, delivered, and reared their own offspring. The offspring were weighed at 5, 10, 15, 20, 25, 30, and some at 35 days of age. They were also tested for exploratory activity in a standard figure-eight "maze" for 30 min/day on days 15, 20, 25, and 30. A second assessment of exploratory behavior, along with a simple test of aversive conditioning, was attempted in the pilot study, but was judged not to be suitable for the main study. Of the 21 male rabbits that were mated in the pilot study, 16 produced viable litters (6/7, 6/7, and 4/7 in control, low- and high-lead groups, respectively), with a mean number of 6 live births/litter in each treatment group (range 2-8). Of the 60 rabbits mated in the main study, 57 produced litters, and two rabbits died giving birth. Significant postnatal deaths were observed in all groups, with about one half of the offspring dying before testing was initiated at day 15. There were no treatment-related effects on offspring weight gain through wearing. The data suggest that paternal lead exposure of rabbits may reduce figure-eight activity on day 25, the time of peak activity in the offspring.

Analysis of Variance↗
PubMedDate not supplied

Developmental toxicity interactions of methanol and radiofrequency radiation or 2-methoxyethanol in rats.

This research was undertaken to determine potential interactions among chemical and physical agents. Radiofrequency (RF) radiation is used in numerous workplaces, and many workers are concurrently exposed to RF radiation and various chemicals. The developmental toxicity of RF radiation is associated with the degree and duration of hyperthermia induced by the exposure. Previous animal research indicates that hyperthermia induced by an elevation in ambient temperature can potentiate the toxicity and teratogenicity of some chemical agents. We previously demonstrated that combined exposure to RF radiation (10 MHz) and the industrial solvent, 2-methoxyethanol (2ME), enhanced teratogenicity in rats. Interactions were noted at even the lowest levels of 2ME tested, but only at hyperthermic levels of RF radiation. The purpose of the present research is to investigate if the interactive effects noted for RF radiation and 2ME are unique to these agents, or if similar interactions might be seen with other chemicals. Because methanol is widely used as a solvent as well as fuel additive, and, at high levels, is teratogenic in animals, we selected methanol as a chemical to address generalizability. Based on the literature and our pilot studies, 0, 2, or 3 g/kg methanol (twice, at 6-hour intervals) were administered on gestation day 9 or 13 to groups of 10 Sprague-Dawley rats. Dams treated on day 9 were given methanol and exposed to RF radiation sufficient to maintain colonic temperature at 41 degrees C for 60 minutes (or sham). Those treated on day 13 were given methanol plus either 0 or 100 mg/kg 2ME. Because we observed that methanol produced hypothermia, some groups were given the initial dose of methanol concurrently with the RF or 2ME, and others were given the first dose of methanol 1.5 hours prior to RF or 2ME. Dams were sacrificed on gestation day 20, and the fetuses were examined for external malformations. The results indicate that RF radiation or methanol on day 9 increased the incidence of resorbed fetuses, but no interactive effects were observed. The resorptions were highest in groups given the experimental treatments 1.5 hours apart. The higher dose of methanol also reduced fetal weights. Administration of 2ME or methanol on day 13 increased the rate of malformations, and there was evidence of a positive interaction between 2ME and methanol. Fetal weights were reduced by 2ME and methanol alone, but no interaction was observed. Also, separation of the dosing with the teratogens did not affect the results. These results point out that interactions in developmental toxicology, such as those of RF radiation, 2ME, and methanol that we have studied, are complex, and such interactions cannot be fully understood or predicted without more research. It is important that combined exposure effects be considered when developing both physical agent and chemical agent exposure guidelines and intervention strategies.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Developmental toxicology of industrial alcohols: a summary of 13 alcohols administered by inhalation to rats.

The developmental toxicology of 13 industrial alcohols (methanol, ethanol, 1-propanol, isopropanol, 1-butanol, 2-butanol, tertiary-butanol, 1-pentanol, 1-hexanol, 2-ethyl-1-hexanol, 1-octanol, 1-nonanol, and 1-decanol), and the behavioral teratogenicity of 4 of these alcohols, were assessed in a series of experiments. The results of individual alcohols have been published previously, but the present paper summarizes the results in view of structure-activity relationships among these alcohols. The alcohols were administered by inhalation for 7 hours per day (6 hours/day for 1-decanol) on gestation days 1-19 to groups of approximately 15 pregnant Sprague-Dawley rats. For developmental toxicology evaluations, dams were sacrificed on gestation day 20. Fetuses were serially removed, weighed, sexed, and examined for external malformations. The frequency of visceral malformations and variations was determined in one-half of the fetuses, and the frequency of skeletal deviations was determined in the other half. Behavioral teratology endpoints were investigated in groups of 15 pregnant rats exposed to one of four alcohols (ethanol, 1-propanol, 1-butanol, and tertiary-butanol) and also involved groups of 18 male rats which were exposed to the same concentrations of each alcohol for 6 weeks, and then mated to untreated females. In the behavioral teratology evaluations, all litters were culled to eight pups and fostered to unexposed mothers. Offspring were tested from days 10-90 on a series of behavioral tests designed to evaluate neuromotor integrity, activity levels, learning, and memory. Additionally, brains were removed from 10 offspring per group at 21 days of age, and were dissected into cerebrum, cerebellum, brainstem, and midbrain; these samples were assayed for steady-state levels of protein and the neurotransmitters acetylcholine, dopamine, norepinephrine, 5-hydroxytryptamine (serotonin), substance P, B-endorphin, and met-enkephalin. Congenital malformations were noted for methanol, 1-propanol, isopropanol, and 1-butanol, but only at concentrations in excess of 5000 ppm. These concentrations also produced toxicity in the maternal animals; thus, there was little evidence of selective developmental toxicity among the alcohols. Although sporadic behavioral and neurochemical deviations were detected, no consistent pattern of effects was seen for any of the alcohols we tested. It should be noted that alcohols with chain lengths longer than the butyl series could not be generated as vapors at sufficiently high concentrations to produce observable toxicity in the maternal animals. This limits the generality of these findings to the possible developmental effects of these alcohols when taken through other routes of exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMedDate not supplied

Collaborative Behavioral Teratology Study: protocol design and testing procedures.

This paper presents background information on the methods used in the Collaborative Behavioral Teratology Study (CBTS), the rationale behind the experimental design, and the design and specific procedures used in the CBTS. Each of the following methods is discussed: negative geotaxis, olfactory discrimination, auditory startle habituation, one-hour activity in the figure-8 maze, visual discrimination learning, 23-hour activity in the figure-8 maze, and amphetamine-stimulated activity. The CBTS was designed to determine the intra- and interlaboratory reliability of these test methods and the detection sensitivity of each method, as well as to determine the importance of several major variables (early test experience, gender, litter). The important design features which permitted these evaluations are discussed. Each laboratory conducted two independent experiments: one using d-amphetamine sulfate as the test agent and one using methylmercuric chloride. Other than the use of different agents and dosing regimens in the two studies, all other characteristics of experimental design were identical. Each study was conducted in four replicates with 4 litters/each of 4 treatment groups/replicate. The replicate design was an important feature which permitted reliability of the tests to be addressed under conditions in which several other sources of variation in responding could be identified and accounted for in the model. Other methods by which optimal testing conditions were implemented in the participating laboratories included the "blind" testing of all subjects in specific orders which were counterbalanced for treatment group, time of day, and the apparatus in which the animals were placed.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗
PubMedDate not supplied

Comparison of behavioral teratogenic effects of ethanol and n-propanol administered by inhalation to rats.

Despite extensive testing of ethanol, there has been little research on the reproductive effects of other alcohols. We investigated the behavioral teratogenicity of inhalation exposures to ethanol and n-propanol. Groups of 18 male (approximately 450 g) and 15 pregnant female Sprague-Dawley rats were exposed 7 hours/day for six weeks or throughout gestation, respectively, to 16 000, 10 000, or 0 ppm ethanol or to 7 000, 35 000, or 0 ppm n-propanol. Pregnant females exposed to 7 000 ppm n-propanol, but not to ethanol, showed reduced weight gain, and female offspring also had reduced weight gain through three weeks of age; there was also slight teratogenicity observed at this concentration. Exposed males were mated with unexposed females; fertility was reduced in males exposed to 7 000 ppm n-propanol (two viable litters from 17 matings), but there were no differences from controls in maternal weight gain, feed intake, or water consumption in any other groups. In both maternally- and paternally-exposed groups, litters were culled to four pups of each sex and fostered to untreated females. One female and one male pup per litter were administered tests of neuromotor coordination (ascent on wire mesh screen, rotorod), activity levels (open field, running wheel), or learning ability (avoidance, operant conditioning), but no significant differences from controls were found with either alcohol, despite the reduction in maternal and female offspring body weight and minimal teratogenicity with 7 000 ppm n-propanol. Calculations for predicting blood ethanol levels with inhalation exposure are also presented.

Animals↗
PubMedDate not supplied

Prenatal interactions between ethanol and the industrial solvent 2-ethoxyethanol in rats: maternal and behavioral teratogenic effects.

Behavioral and neurochemical deviations in the offspring of rats exposed to 100 ppm ethoxyethanol during gestation have been reported previously. Since this compound is likely metabolized in the same manner as ethanol, the present study investigated the interactive effects of ethanol and ethoxyethanol on prenatal development. Groups of 15-20 pregnant Sprague-Dawley rats were given 10% ethanol in the drinking water with or without concomitant inhalation exposure to 100 ppm ethoxyethanol during gestation days 7-13 or 14-20. Another group was exposed to 200 ppm ethoxyethanol on gestation days 7-13, and sham-exposed controls were included for both gestation periods. Ethanol alone on days 14-20 and 200 ppm ethoxyethanol reduced overall weight gain during pregnancy. As in the previous research, pregnancy duration was extended in the groups given ethoxyethanol, but not in groups given ethanol alone. Neuromotor ability, as assessed by an ascent test and by a rotorod, was reduced by 200 ppm ethoxyethanol and by ethanol alone on gestation days 7-13. The group given ethanol plus ethoxyethanol on days 14-20 spent significantly longer in the start area of an open field, and this group as well as that given 200 ppm ethoxyethanol were less active than controls in the open field and in the shuttle box. When compared with previous research, it appears that ethanol early in gestation may reduce the effects, but later in gestation may enhance the effects of prenatal ethoxyethanol.

Animals↗