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B K Nelson

Publications and source records attributed to B K Nelson.

At least 37 records · Page 2Linked to original sources
PubMed1994

Interactions in developmental toxicology: a literature review and terminology proposal.

Developmental toxicologists have investigated the interactive effects from concurrent exposures to a variety of chemical and physical agents, including therapeutic drugs, industrial agents, and some biological organisms or their toxins. Of approximately 160 reports of concurrent exposures reviewed in this paper, about one third report no interactive effects (including additive effects--usually referring to response--as opposed to dose-additivity); another one third report antagonistic effects, and the final third report potentiative or synergistic effects. The quality of the studies is highly variable. Frequently, only small numbers of animals were included, and very few dose levels were evaluated. Maternal toxicity was rarely discussed. Time-effect relationships were examined infrequently. In addition, these studies are also inconsistent in the use of terms to describe interactive effects, and more than 90% of the terms were not in harmony with currently accepted definitions in toxicology. Because interaction studies will continue to be important in the future, this paper proposes uniform usage of terms for additivity and interactions in developmental toxicology: additivity (the combined effect of two or more developmental toxicants approximates the sum of the effects of the agents administered separately); antagonism (the combined effect of two or more agents, one or more of which are present at doses that would be developmentally toxic if given individually, is significantly less than the sum of the effects of the agents administered separately); potentiation (the increased effect of a developmental toxicant by concurrent action of another agent at a dose that is not developmentally toxic); synergism (the combined effect of two or more developmental toxicants is significantly greater than the sum of the effects of each agent administered alone); and, interaction if more precise terminology does not apply.

Animals↗
PubMed1994

Interactive developmental toxicity of radiofrequency radiation and 2-methoxyethanol in rats.

Concurrent exposures to chemical and physical agents occur in the workplace; exposed workers include those involved with the microelectronics industry, plastic sealers, and electrosurgical units. 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 radiofrequency (RF; 10 MHz) radiation, which also induces hyperthermia and is teratogenic to exposed animals, and the industrial solvent, 2-methoxyethanol (2ME), produces enhanced teratogenicity in rats. The present study replicates and extends the previous research investigating the enhanced teratogenicity of combined RF radiation and 2ME exposures. The interactive dose-related teratogenicity of RF radiation (sham exposure or maintaining colonic temperatures at 42.0 degrees C for 0, 10, 20, or 30 min) and 2ME (0, 75, 100, 125, or 150 mg/kg) was investigated by administering various combinations of RF radiation and 2ME to groups of rats on gestation days 9 or 13; gestation-day 20 fetuses were examined for external, skeletal, and visceral malformations. The results are consistent with and extend our previous research findings. Synergism was observed between RF radiation and 2ME for some treatment combinations, but not for others. The study also clarified which gestational periods, RF radiation exposure durations, and 2ME doses would be most informative in future interaction studies to determine the lowest interactive effect level. Day 9 exposures generally evidenced little effect by 2ME, either by itself or in combination with RF radiation. In contrast, day 13 exposures resulted in highly significant effects from 2ME and RF radiation. The structures showing strong evidence of effects from both 2ME and RF radiation after exposure on gestation day 13 were the forepaw digits, forepaw phalanges, hindpaw digits, hindpaw phalanges, hind limbs, metacarpals, and metatarsals. Statistical analyses did not show a global synergistic effect, but did show evidence for a synergistic effect at intermediate levels of the dose ranges. Future research will address potential interactions at lower doses.

Abnormalities, Drug-Induced↗
PubMed1994

Combined chemical, physical hazards make exposures harder to calculate. Studies show multiple exposures must be evaluated wholly rather than 'adding up' individual risks.

Clearly, current research adds to the mounting scientific evidence that combined exposures can produce greater toxicity than would be predicted using an additive model. Although there is not yet a quantitative method to determine the risks associated with multiple exposures, safety and health specialists must begin to consider the health effects from the entire work process, rather than individual chemical or physical agents. Moreover, organizations involved in risk assessment and standard-setting must evaluate the interactive effects of combined chemical and physical agent exposures. This will make personnel exposure standards comprehensive in addressing realistic occupational health risks.

Animals↗
PubMed1991

Evidence for behavioral teratogenicity in humans.

Central to both the scientific development of behavioral teratology and the attention paid to this field as an important area of study is establishing that prenatal exposure of pregnant females to exogenous agents leads to neurobehavioral disorders in their offspring. This tenet may not be questioned by the majority of toxicologists, but others may not be convinced. This paper serves as a brief review of the accumulated evidence that prenatal exposure to a number of drugs and environmental/industrial agents produces behavioral disorders in human infants.

Behavior↗
PubMed1991

Marked increase in the teratogenicity of the combined administration of the industrial solvent 2-methoxyethanol and radiofrequency radiation in rats.

Limited published animal research reports synergistic teratogenic effects following combined hyperthermia (induced by elevated ambient temperature) and administration of chemical teratogens. Radiofrequency (RF) radiation is widely used in occupational environments. Since RF radiation also elevates the body temperature of, and is teratogenic to, exposed animals, concurrent RF radiation and chemical agent administration may enhance teratogenicity. The present exploratory study, consisting of preliminary dose-finding studies and the primary study, was designed to investigate whether concurrent exposure of rats to RF radiation and the industrial solvent 2-methoxyethanol (2ME) can enhance the developmental toxicity of either agent acting alone. Preliminary dose-finding studies using small numbers of rats investigated the ability of various RF radiation conditions and doses of 2ME to produce external malformations (primarily of the paws) when administered on gestation day 13. Based on these preliminary studies, RF radiation exposure [sufficient to elevate rectal temperature to 42.0 degrees C (4 degrees C above normal for rats) for 30 min] and 2ME administration (150 mg/kg) were selected for the primary study. In the primary study, groups of 18 to 27 pregnant rats were administered RF radiation exposure and distilled water gavage, 2ME gavage and sham RF exposure, RF radiation exposure and 2ME gavage concurrently, or sham RF exposure and distilled water gavage. Pregnant rats were sacrificed on gestation day 20, and the offspring were examined for external malformations. Combined exposures enhanced the adverse effects produced by either experimental agent alone (no malformations were detected in the double sham group). Mean fetal malformations/litter increased from 14% after 2ME and sham RF (15/26 litters affected, with an average of 2 fetuses/litter malformed) and 30% after RF radiation and water gavage (10/18 litters affected, with an average of 4 fetuses/litter malformed), to 76% after the combined treatment (18/18 litters affected, with an average of 12 fetuses/litter malformed). In addition to a significant increase in the frequency of malformations, the severity of malformations also was enhanced by the combination treatment (on a relative severity ranking scale, the 2ME severity score was less than 1, the RF score was 3, and the combination score was 6). This study provided evidence of synergism between RF radiation and 2ME administration, but additional research will be required to characterize the extent of synergism between these two agents. Potential interactive effects between chemical and physical agents need to be investigated to determine the extent to which such interactions should impact occupational exposure standards.

Animals↗
PubMed1989

Lack of selective developmental toxicity of three butanol isomers administered by inhalation to rats.

As part of an ongoing study of the developmental toxicology of industrial alcohols, this report presents the results of the teratology assessments of 1-butanol, 2-butanol, and t-butanol administered by inhalation to rats. Groups of approximately 15 Sprague-Dawley rats were exposed at 8000, 6000, 3500, or 0 ppm 1-butanol, 7000, 5000, 3500, or 0 ppm 2-butanol, or 5000, 3500, 2000, or 0 ppm t-butanol for 7 hr/day on Gestation Days 1-19 (sperm = 0). In each case, the highest concentration was selected to produce maternal toxicity. Dams were sacrificed on Gestation Day 20, and fetuses were individually weighed, tagged, and examined for external malformations. One-half of the fetuses were stained and examined for skeletal abnormalities, and the other half were examined for visceral defects using the Wilson technique. For each butanol isomer examined, the highest concentration (and the intermediate in some cases) was maternally toxic, as manifest by reduced weight gain and feed intake. Even at a maternally toxic dose, and in spite of a dose-dependent reduction in fetal weights for each isomer, the only teratogenicity observed was a slight increase in skeletal malformations (primarily rudimentary cervical ribs), seen with the highest concentration of 1-butanol. Thus, although teratogenicity was observed at 8000 ppm 1-butanol, and developmental toxicity was observed with each of the butyl alcohol isomers studied, concentrations 50 times the current permissible exposure limits for these three butanol isomers do not produce teratogenicity in rats.

Administration, Inhalation↗
PubMed1988

Teratogenicity of n-propanol and isopropanol administered at high inhalation concentrations to rats.

As part of a teratological evaluation of several alcohols, 10,000, 7000 and 3500 ppm n-propanol or isopropanol were administered by inhalation to groups of 15 pregnant Sprague-Dawley rats for 7 hr/day on gestation days 1-19. The dams were killed on day 20. Half of the foetuses were examined for skeletal defects and the others for visceral defects using the Wilson technique. The highest concentration of n-propanol produced only minimal maternal toxicity, as indicated by observation and by measurement of weight gain and feed and water intake. In contrast, the same concentration of isopropanol produced narcosis in the dams, retarded body-weight gain and reduced the feed intake. At 7000 ppm isopropanol, body-weight gain was retarded but there were no other observable effects in the dams. Following exposure to 10,000 ppm of either alcohol, there were significant (P less than or equal to 0.05) increases in resorptions and decreases in foetal weights compared with the control groups. Foetal weights were also reduced significantly following exposure to 7000 ppm of either alcohol and to 3500 ppm isopropanol. Significantly more litters had malformations following exposure to 10,000 or 7000 ppm of either alcohol, but these effects were seen only in the presence of maternal toxicity. At 3500 ppm, no detectable teratogenic effects were produced by either solvent.

1-Propanol↗
PubMed1987

Accuracy of urine urobilinogen and bilirubin assays in predicting liver function test abnormalities.

Components of the dipstick urinalysis (urine urobilinogen and urine bilirubin) are often used by emergency physicians to screen for the need to obtain liver function tests in many clinical situations. A prospective observational study was conducted to evaluate the sensitivity, specificity, and predictive properties of spot urine bilirubin and urobilinogen assays in the emergency department as screening test for serum liver function test (LFT) abnormalities. Of 122 patients, abdominal pain was the indication for laboratory evaluation in 54%; jaundice and constitutional symptoms were the indication in 29%. Overall sensitivities for both urine assays were 70% to 74% for serum bilirubin, but 43% to 53% for other LFTs; specificities were 77% to 87% for both urine screens. Positive predictive values show that the urine assays were 83% to 86% reliable for detecting at least one LFT abnormality. Negative predictive values were 85% for both urine assays for serum bilirubin elevations, but lower for other LFTs. Urine urobilinogen has its greatest clinical utility as a screen when a normal/abnormal threshold of 2.0/4.0 mg/dL is used.

Adolescent↗
PubMed1986

Developmental neurotoxicology of in utero exposure to industrial solvents in experimental animals.

In summary, relatively few solvents have been examined for developmental neurotoxicology. Although most of the studies have not been replicated, the majority of the solvents tested have produced significant differences from controls. Many used inhalation, which is often the most likely route of occupational or environmental exposure. The majority have extended the exposure for much of gestation of rats. The extensive usage of solvents and the proportion of those tested which have produced positive effects (although admittedly some not at environmentally-relevant exposure concentrations), make a strong case for additional testing of industrial solvents for developmental neurotoxicology.

Animals↗
PubMed1985

Teratological assessment of methanol and ethanol at high inhalation levels in rats.

Alcohols are widely used as industrial solvents. In spite of the fact that ethanol is a human teratogen, there has not been systematic investigation of the potential teratogenic effects of other alcohols, particularly using the inhalation route of exposure, as would be appropriate in assessing occupational and environmental types of experience. As part of a large teratological examination of industrial alcohols, methanol and ethanol were administered by inhalation to groups of approximately 15 pregnant Sprague-Dawley rats. Methanol was administered at 20,000 ppm (20ME), 10,000 ppm (10ME), 5000 ppm (5ME), and 0 ppm (MECO) for 7 hr/day on Days 1-19 of gestation (Days 7-15 for 20ME). Ethanol was administered at 20,000 ppm (20ET), 16,000 ppm (16ET), 10,000 ppm (10ET), and 0 ppm (ETCO) for 7 hr/day on Days 1-19 of gestation. Dams were sacrificed on Day 20 (sperm = Day 0). One-half of the fetuses were examined using the Wilson technique for visceral defects, and the other half were examined for skeletal defects. The highest concentration of methanol (20ME) produced slight maternal toxicity and a high incidence of congenital malformations (p less than 0.001), predominantly extra or rudimentary cervical ribs and urinary or cardiovascular defects. Similar malformations were seen in the 10ME group, but the incidence was not significantly different from controls. No adverse effects were noted in the 5ME group. Dams in the 20ET group were narcotized by the end of exposure, and maternal weight gain and feed intake were decreased during the first week of exposure. The 16ET dams had slightly depressed weight gain (p less than 0.01) during the first week of exposure, but there were no significant effects on feed consumption. There was no definite increase in malformations at any level of ethanol, although the incidence in the 20ET group was of borderline significance.

Abnormalities, Drug-Induced↗
PubMed1984

Behavioral and neurochemical alterations in the offspring of rats after maternal or paternal inhalation exposure to the industrial solvent 2-methoxyethanol.

The industrial solvent 2-methoxyethanol (2ME) has antifertility effects in male rats at 300 ppm and is teratogenic in rats and rabbits at 50 ppm. The present research investigated if exposure of paternal or maternal animals to 25 ppm 2ME, the current U.S. permissible occupational exposure limit, would produce detectable effects in the offspring. Eighteen male young-adult Sprague-Dawley rats were exposed to 25 ppm 2ME 7 hr/day, 7 days/week for 6 weeks; they were then mated with untreated females which were allowed to deliver and rear their young. In addition, groups of 15 pregnant rats were exposed 7 hr/day on gestation days 7-13 or 14-20 and allowed to deliver and rear their young. At birth, litters were culled to 4 females and 4 males for behavioral testing of neuromotor function, activity, and simple learning ability on days 10 through 90. In addition, brains from newborn and 21-day-old offspring were analyzed for neurochemical deviations from controls. No effects on paternal or maternal animals, nor on the number or weight of live offspring, were noted. Behavioral testing revealed significant differences from controls only in avoidance conditioning of offspring of mothers exposed on days 7-13. In contrast, neurochemical deviations were observed in brains from 21-day-old offspring from the paternally exposed group as well as from both maternally exposed groups; changes were numerous in the brainstem and cerebrum but were fewer in the cerebellum and midbrain. Thus it appears that both paternal and maternal inhalation of 25 ppm 2ME produces some effect which is reflected in neurochemical deviations in the offspring.

Acetylcholine↗
PubMed1984

Reproductive toxicity of the industrial solvent 2-ethoxyethanol in rats and interactive effects of ethanol.

The solvent, 2-ethoxyethanol, induced complete embryomortality in pregnant rats exposed to three times the current Federal permissible exposure limit (PEL). Following exposure to ethoxyethanol at a concentration only one-half the current PEL, the offspring evidenced behavioral and neurochemical deviations from controls. Subsequent studies found that ingestion of ethanol with concomitant inhalation of ethoxyethanol vapors early in pregnancy appeared to reduce the number of both behavioral and neurochemical deviations found for ethoxyethanol. In contrast, the concomitant exposure to ethanol and ethoxyethanol later in gestation potentiated the behavioral and neurochemical effects of ethoxyethanol. This research indicates that the industrial solvent 2-ethoxyethanol presents an occupational reproductive hazard and raises the issue of the importance of an interaction of social habits with occupational exposure to such hazards. The results would suggest that occupational physicians should advise pregnant workers in the chemical industry of the adverse effects of ethanol during pregnancy and of the possible interactions with other chemicals and should encourage them to be especially cautious with ethanol consumption since they may be at greater risk.

Air Pollutants, Occupational↗
PubMed1984

Comparative inhalation teratogenicity of four glycol ether solvents and an amino derivative in rats.

Previous research demonstrated the inhalation teratogenicity of the solvent 2-ethoxyethanol in rats and rabbits. As this is one of a class of widely used industrial solvents, we investigated the teratogenicity of five structurally related compounds. Each chemical was vaporized and administered to approximately 15 pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects. Data were analyzed on a litter basis; three solvents were compared with a pooled group (N = 34) of sham-exposed controls, and the remaining two were compared with a group of 15 controls. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occurred at both 100 and 50 ppm. 2-ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. In summary, shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether, both patterns predictable from the biochemical literature.

Abnormalities, Drug-Induced↗
PubMed1984

Behavioral teratology of ethylene glycol monomethyl and monoethyl ethers.

A recent addition to the field of teratology has been the inclusion of functional assessment techniques of offspring after prenatal exposure to exogenous agents. The present paper reviews the behavioral teratogenic effects of ethylene glycol monomethyl ether (EGME, 2-methoxyethanol) and ethylene glycol monoethyl ether (EGEE, 2-ethoxyethanol). Groups of 15 pregnant Sprague-Dawley rats were exposed via inhalation to 25 ppm EGME or to 100 ppm EGEE on gestation days 7 to 13 or 14 to 20. An equal number of sham-exposed controls were included for both periods of gestation. The only effect noted in the maternal animals was a slightly prolonged gestation in the group exposed to 100 ppm EGEE on days 14 to 20. Litters were culled to four female and four male pups on the day of birth. Pups of each sex from all litters were tested on a variety of behavioral tasks (including tests of neuromuscular ability, activity, and learning ability) extending from postnatal days 10 to 90. In addition, brains from newborn and from 21-day-old offspring were removed and analyzed for concentrations of the neurotransmitters acetylcholine, dopamine, norepinephrine, and 5-hydroxytryptamine (serotonin). Both the behavioral testing and the neurochemical evaluations revealed functional alterations in the litter groups experiencing prenatal exposure to EGME and EGEE at concentrations which produced no observable effects in the maternal animals.

Air Pollutants, Occupational↗