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Biomedical subjects

C Bevan

Publications and source records attributed to C Bevan.

At least 19 recordsLinked to original sources
PubMed2005

Exposure to repeat doses of antenatal glucocorticoids is associated with altered cardiovascular status after birth.

OBJECTIVE: To determine if exposure to more than one course of antenatal glucocorticoids is associated with changes in infant blood pressure and myocardial wall thickness in the first month after birth. DESIGN: Prospective cohort study. SETTING: Tertiary neonatal intensive care unit. PARTICIPANTS: Mothers who were eligible for but declined to enter a randomised trial of repeated doses of antenatal glucocorticoids (ACTORDS)-that is, who had a singleton, twin, or triplet pregnancy at <32 weeks gestation, had received an initial course of glucocorticoids seven or more days previously, and were considered to be at continued risk of preterm birth. MAIN OUTCOME MEASURES: Blood pressure daily for the first week then weekly until 4 weeks of age. End diastolic interventricular septal and left ventricular posterior wall (EDIVS and EDLVPW) thickness at 48-72 hours after birth. RESULTS: Thirty seven women were enrolled and delivered 50 infants. Thirty mothers (39 infants) were exposed to one course of glucocorticoids, and seven mothers (11 infants) to more than one course. Blood pressures were higher in the first week after birth in infants exposed to multiple courses of glucocorticoids, and in infants with a latency between last exposure and delivery of less than seven days. Systolic blood pressure on day 1 was >2SD above published normal ranges in 67% of babies exposed to multiple courses and 24% of babies exposed to a single course of glucocorticoids (p = 0.04). There was no difference between groups in thickness of the EDIVS or EDLVPW. However, 44/50 (88%) babies had EDIVS and 49/50 (98%) babies had EDLVPW thickness >2 SD above the expected mean for birth weight and gestation. EDIVS but not EDLVPW thickness increased with increasing latency (mean 0.02 mm/day, p = 0.03). CONCLUSION: Future randomised trials should assess the long term effects of exposure to antenatal glucocorticoids, particularly multiple courses, on the cardiovascular status of the infant.

Adult↗
PubMed2001

Unique selectivity of perfluorinated stationary phases with 2,2,2-trifluoroethanol as organic mobile phase modifier.

The selectivity of Luna C18 Xterra C18 and Fluophase (perfluorinated C6) stationary phases has been investigated with aqueous acetonitrile, methanol and 2,2,2-trifluoroethanol mobile phases using linear solvation equations. The gradient retention times of a set of 60 compounds with known molecular descriptors have been determined. Linear solvation equations have been set up to describe the relationship between the gradient retention times and the molecular properties. The selectivity of the stationary phase/mobile phase systems was characterised by the regression coefficients of the molecular descriptors. The perfluorinated stationary phase showed very different selectivity using 2,2,2-trifluoroethanol (TFE) as co-solvent. Compounds with H-bond donor functionality were retained much less than in the other investigated high-performance liquid chromatography (HPLC) systems. This unique selectivity can be explained by the stronger adsorption of trifluoroethanol on the perfluorinated stationary phase surface, than on the hydrocarbon surface. It suggests the importance of the adsorbed organic modifiers in the separation mechanism during reversed-phase HPLC.

Chromatography, High Pressure Liquid↗
PubMed2001

Effect of 4-vinylcyclohexene on micronucleus formation in the bone marrow of rats and mice.

This study was conducted to evaluate the potential of 4-vinylcyclohexene (VCH) to induce micronuclei in the bone marrow of mice and rats. Male and female Crl:CD BR (Sprague-Dawley) rats and B6C3F1/CrBR mice were exposed to VCH 6 hr/day for 2 days or for 13 weeks. In the 2-day study, mice were exposed by inhalation to 0, 250, 500, or 1000 ppm, and rats were exposed to 0, 500, 1000, or 2000 ppm. In the 13-week study, mice were exposed to 0, 50, 250, or 1000 ppm, and rats were exposed to 0, 250, 1000, or 1500 ppm. In each study, a separate group of mice was exposed to 1000 ppm 1,3-butadiene (BD) so that a comparison could be made between the two compounds. Likewise, cyclophosphamide was also included for rats as a positive control. Bone marrow was collected from VCH-exposed animals approximately 24 h and 48 h after the final exposure. There were no statistically significant increases in micronucleatedpolychromatic erythrocytes (MN-PCEs) among VCH-treated mice and rats at any dose level or sampling interval at either 2-days or 13-weeks. Also, no statistically significant differences in the polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) ratios were observed in any of the VCH-treated mice and rats compared to air-exposed animals. As expected, both the butadiene-treated mice and the cyclophosphamide-treated rats showed significantly more MN-PCEs than the control animals.

Administration, Inhalation↗
PubMed2001

Analysis of the steroid receptor coactivator 1 (SRC1)-CREB binding protein interaction interface and its importance for the function of SRC1.

The transcriptional activity of nuclear receptors is mediated by coactivator proteins, including steroid receptor coactivator 1 (SRC1) and its homologues and the general coactivators CREB binding protein (CBP) and p300. SRC1 contains an activation domain (AD1) which functions via recruitment of CBP and and p300. In this study, we have used yeast two-hybrid and in vitro interaction-peptide inhibition experiments to map the AD1 domain of SRC1 to a 35-residue sequence potentially containing two alpha-helices. We also define a 72-amino-acid sequence in CBP necessary for SRC1 binding, designated the SRC1 interaction domain (SID). We show that in contrast to SRC1, direct binding of CBP to the estrogen receptor is weak, suggesting that SRC1 functions primarily as an adaptor to recruit CBP and p300. In support of this, we show that the ability of SRC1 to enhance ligand-dependent nuclear receptor activity in transiently transfected cells is dependent upon the integrity of the AD1 region. In contrast, the putative histone acetyltransferase domain, the Per-Arnt-Sim basic helix-loop-helix domain, the glutamine-rich domain, and AD2 can each be removed without loss of ligand-induced activity. Remarkably, a construct corresponding to residues 631 to 970, which contains only the LXXLL motifs and the AD1 region of SRC1, retained strong coactivator activity in our assays.

Amino Acid Motifs↗
PubMed2001

Rapid method for the estimation of octanol/water partition coefficient (log P(oct)) from gradient RP-HPLC retention and a hydrogen bond acidity term (zetaalpha(2)(H)).

We propose a rapid method for the measurement of octanol/water partition coefficients (log P(oct)) via fast gradient reversed phase retention and the calculation of the hydrogen bond acidity of the compounds. The cycle time of the generic gradient HPLC method is 5 minutes. The general solvation equation obtained for the log Poct values and the fast gradient Chromatographic Hydrophobicity Indices with acetonitrile (CHI(ACN)) and methanol

Chemical Phenomena↗
PubMed2000

Mother, daughter, patient, nurse: women's emotion work in aged care.

This paper examines emotion work within the predominantly female environment of aged-care nursing, identifying phenomena which must be accounted for in a theory of emotional labour. These phenomena include the blurring of public and private in women's experiences and maternal models of care. Initial findings demonstrate the high levels of stress experienced by staff, related to emotional labour and to conflicts around the erosion of care standards. Sixteen women, from rural Australia, participated in the first stage of the research. The oldest was in her sixties, the youngest in her thirties. Length of aged-care experience ranged from 2 to 33 years. Although most of the women expected to still be in aged care in 5 years' time, they were negative in their attitudes to personal ageing, suggesting an ambivalence in their feelings about working in aged care. Three women nurses are the particular focus of this paper. Their narratives illustrate the intersection of private and public caring in nurses' lives and the implications of this for emotional labour. Phenomena such as dual caring, conflicts in insider-outsider roles, and transference are revealed in their narratives. We argue that the welfare of the recipient of gerontic nursing is linked to the well-being of the nurse-carer but that a cultural change is needed so as to recognize and value emotion work. However, endorsing Staden, we agree that such a change is dependent on the politicization of 'caring'. There is also need for further and broader research concerning the nature of emotional labour and the ethics of care.

Adult↗
PubMed2000

Reproduction/developmental toxicity screening test in rats with orally-administered 1-hexene.

This study was conducted to provide screening information concerning the potential systemic, reproductive and developmental toxicity of 1-hexene when administered orally, by gavage, to male and female rats using a modified OECD 421 protocol. 1-Hexene was administered at doses of 100, 500, and 1000 mg/kg/day in corn oil; the control group received the vehicle at an equivalent volume. The males were treated for 28 days prior to mating and until euthanasia (44 days of dosing). The females were treated for 14 days prior to mating and during mating, gestation, and lactation until euthanasia (41-55 total days of dosing). Females were allowed to deliver and rear their offspring until lactation day 4. The parental rats were subject to a gross and microscopic examination. Viability and development of the pups were followed through lactation day 4. There was no mortality, and there were no clinical signs of toxicity or differences in body weights, weight gain, feed consumption or organ weights. Copulation and fertility indices, precoital intervals, gestation lengths and pregnancy rates were comparable among the groups, and no signs of prolonged delivery or unusual nesting behaviors were noted. Pup viability, body weights, external observations and necropsy data were comparable among the groups. Pitted kidneys were observed at necropsy for two parental males in the 500 mg/kg/day group and three males in the 1000 mg/kg/day group. Microscopic changes in the kidneys of some male rats from the 100, 500, and 1000 mg/kg/day groups consisted of dose-related accumulations of hyaline droplets in the epithelial cells of the proximal convoluted tubules of the kidneys. In summary, the only treatment-related effect noted in this study was hydrocarbon nephropathy in male rats, which is not considered relevant for human health. The NOAEL for systemic and reproductive toxicity was 1000 mg/kg/day, excluding the finding of male rat hydrocarbon nephropathy.

Administration, Oral↗
PubMed2000

Characterizing the selectivity of stationary phases and organic modifiers in reversed-phase high-performance liquid chromatographic systems by a general solvation equation using gradient elution.

Retention data for a set of 69 compounds using rapid gradient elution are obtained on a wide range of reversed-phase stationary phases and organic modifiers. The chromatographic stationary phases studied are Inertsil (IN)-ODS, pentafluorophenyl, fluoro-octyl, n-propylcyano, Polymer (PLRP-S 100), and hexylphenyl. The organic solvent modifiers are 2,2,2-trifluoroethanol (TFE); 1,1,1,3,3,3-hexafluoropropan-2-ol (HFIP); isopropanol; methanol (MeOH); acetonitrile (AcN); tetrahydrofuran; 1,4-dioxane; N,N-dimethylformamide; and mixed solvents of dimethylsulfoxide (DMSO) with AcN and DMSO with MeOH (1:1). A total of 25 chromatographic systems are analyzed using a solvation equation. In general, most of the systems give reasonable statistics. The selectivity of the reversed phase-high-performance liquid chromatographic (HPLC) systems with respect to the solute's dipolarity-polarity, hydrogen-bond acidity, and basicity are reflected in correspondingly large coefficients in the solvation equation. We wanted to find the most orthogonal HPLC systems, showing the highest possible selectivity difference in order to derive molecular descriptors using the gradient retention times of a compound. We selected eight chromatographic systems that have a large range of coefficients of interest (s, a, and b) similar to those found in water-solvent partitions used previously to derive molecular descriptors. The systems selected are IN-ODS phases with AcN, MeOH, TFE, and HFIP as mobile phase, PLRP-S 100 phase with AcN, propylcyano phase with AcN and MeOH, and fluorooctyl phase with TFE. Using the retention data obtained for a compound in the selected chromatographic systems, we can estimate the molecular descriptors with the faster and simpler gradient elution method.

Journal Article↗
PubMed2000

Intravenous clonidine infusion in critically ill children: dose-dependent sedative effects and cardiovascular stability.

Clonidine is used for analgesia and sedation in paediatric anaesthesia, but there are no data on its sedative properties and side effects in critically ill children. We studied 30 ventilated children aged 10 yr and under to determine an effective i.v. dosing range and to assess its cardiovascular effects. Twenty non-paralysed, ventilated children were given a background infusion of midazolam 50 micrograms kg-1 h-1 combined with a variable clonidine infusion (0.1-2 micrograms kg-1 h-1) to maintain optimal sedation. The effects of clonidine 1 microgram kg-1 h-1 on cardiac index were measured in 10 postoperative cardiac patients using a reverse Fick method. Dose-dependent sedation was achievable (713 out of 861 h) without cardiovascular side effects, but an infusion limit of clonidine 1 microgram kg-1 h-1 was inadequate in two patients. An increased dose limit of 2 micrograms kg-1 h-1 combined with midazolam 50 micrograms kg-1 h-1 achieved satisfactory sedation scores for 602 out of a total of 672 h studied with no failures. Clonidine in combination with midazolam at 1 microgram kg-1 h-1 was not associated with significant changes in heart rate arterial pressure or cardiac index.

Adrenergic alpha-Agonists↗
PubMed1998

Dermal absorption and pharmacokinetics of isopropanol in the male and female F-344 rat.

Isopropanol (IPA), as a 70% aqueous solution, was applied under occluded conditions to the shaved backs of male and female Fischer F-344 rats for a period of 4 hr. Maximum analyzed blood concentrations of IPA were attained at 4 hr and decreased steadily following removal of the test material. Blood concentrations were below the limit of quantification at 8 hr. Acetone (ACE) blood levels rose steadily during the 4-hr exposures and continued to rise following removal of the test material, reaching peak analyzed levels at 4.5 hr (male) and 5 hr (females). ACE blood concentrations were below the limit of quantification at 24 hr. Basic pharmacokinetic parameters were similar for male and female rats with mean, first-order elimination half-lives for IPA and ACE of 0.8 to 0.9 hr and 2.1 to 2.2 hr, respectively. Following iv administration of [14C]IPA, 50-55% of the dose was eliminated as 14CO2 with lesser amounts recovered as expired volatiles or in urine. Total recoveries following iv administration were 83% for both males and females. Following a 4-hr dermal exposure to [14C]IPA (70% aqueous solution), 84-86% of the dose was recovered from the application site. Dermal absorption rates were calculated by two independent methods. The values obtained were 0.78 +/- 0.03 and 0.85 +/- 0.04 mg/cm2/hr for males and 0.77 +/- 0.13 and 0.78 +/- 0.16 mg/cm2/hr for females. Calculated permeability coefficients of 1.37 to 1.50 x 10(-3) cm/hr for males and 1.35 to 1.37 x 10(-3) cm/hr for females indicate that in the rat, IPA is rapidly absorbed dermally when applied under occluded conditions.

2-Propanol↗
PubMed1997

Two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) in rats.

A two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) was conducted in Sprague-Dawley rats. Twenty-five rats of each sex (F0) were exposed by inhalation to 0, 400, 3000 or 8000 ppm MTBE vapor, 6 h a day for 10 weeks prior to mating. Parental animals were then mated within groups for up to 3 weeks. Parental females were exposed during mating, gestation and lactation (starting on day 5); parental males were exposed during mating through delivery of their last litter sired. The F1 adults were selected from the F1 litters and were exposed beginning on postnatal day 28 for at least 8 weeks before mating to produce F2 litters. During exposures to 3000 and 8000 ppm MTBE, group observations included hypoactivity and lack of startle reflex in parental animals from both generations. Parental animals at 8000 ppm were also ataxic. During the pre-mating period, body weights of the 8000 ppm males from both generations and the F1 females were significantly reduced compared to control animals. Transient body weight reduction was also observed in the 3000 ppm F1 males and females during the pre-mating period. Lactational body weights were increased in the 8000 ppm females from both generations. In the F1 generation, increased liver weights were noted in the 3000 and 8000 ppm animals for both sexes, although histopathological examination revealed no treatment-related effects. There were no treatment-related reproductive effects noted in any of the parameters measured in this study. Offspring survival was equivalent among treated and control groups from both generations, and there were no remarkable post-mortem findings. There was, however, a significant increase in dead F2 pups in the 8000 ppm group on postnatal day 4. The F1 litters at 3000 and 8000 ppm had lowered body weights from postnatal days 14-21 and 14-28, respectively. The F2 generation of pups at 3000 and 8000 ppm also exhibited lowered body weights from postnatal days 14-28 and 7-28, respectively. Body weight gains in both the F1 and F2 litters were also reduced for the corresponding time intervals. Thus, exposure to MTBE vapor produced no reproductive toxicity to two generations of Sprague-Dawley rats even in the presence of parental toxicity at 3000 and 8000 ppm. Postnatal toxicity was observed in the offspring of both generations, but only in the presence of maternal toxicity. The no-observed-effect level (NOEL) for both parental and postnatal toxicity is 400 ppm, and the NOEL for reproductive toxicity is at least 8000 ppm.

Administration, Inhalation↗
PubMed1997

Developmental toxicity evaluation of methyl tertiary-butyl ether (MTBE) by inhalation in mice and rabbits.

Pregnant CD-1 mice (30 per group) and female New Zealand White rabbits (15 per group) were exposed by inhalation to 0, 1000, 4000 and 8000 ppm methyl tertiary-butyl ether (MTBE) vapor for 6 h a day during gestational days (GD) 6-15 and 6-18, respectively. Maternal body weights, clinical observations and food consumption were recorded throughout gestation for both species. At scheduled euthanization (GD 18 for mice and GD 29 for rabbits), fetuses were weighed, sexed and examined for external, visceral (including craniofacial) and skeletal alterations. For both species, the pregnancy rate was high and equivalent across all groups; no pregnant animals died or aborted. There were no does that delivered early, but there were three mouse dams in the control group and two dams in the 4000 ppm group that delivered early and were removed from the study. In mice, maternal body weights, body weight gain, corrected maternal gestational weight change and food consumption were significantly reduced in mice at 8000 ppm. Hypoactivity and ataxia were observed in dams exposed to 4000 and 8000 ppm. Gestational parameters affected at 8000 ppm included post-implantation loss (due to increased late resorptions and dead fetuses) and altered sex ratio (decreased males); fetal body weights per litter were reduced at 4000 and 8000 ppm. There was a significantly increased incidence of cleft palate at 8000 ppm; this resulted in increased incidences of pooled external and visceral malformations and of total malformations at this exposure concentration. There were also treatment-related increases in the incidence of individual skeletal variations at 4000 and 8000 ppm. In rabbits, maternal weight gain and food consumption were significantly reduced at 4000 and 8000 ppm. Relative liver weights were also reduced at 8000 ppm. All gestational parameters were equivalent across all groups, including pre- and post-implantation loss, fetal sex ratios, litter size and fetal weights/litter. There was no evidence of treatment-related teratogenicity observed at any dose tested in rabbits. The no-observed-effect levels (NOELs) for maternal and developmental toxicity were both 1000 ppm in mice and 1000 ppm and at least 8000 ppm, respectively, in rabbits.

Abnormalities, Multiple↗
PubMed1997

Isopropanol vapor inhalation oncogenicity study in Fischer 344 rats and CD-1 mice.

The potential oncogenic effects of isopropanol, a widely used solvent, were investigated. Four groups of animals, each consisting of 75 CD-1 mice/sex and 75 Fischer 344 rats/sex, were exposed to isopropanol vapor (CAS No. 67-63-0) at target concentrations of 0 (filtered air control), 500, 2500, or 5000 ppm. Animals assigned to the core group (55 mice/sex/group and 65 rats/sex/group) were exposed for 6 hr/day, 5 consecutive days/week for at least 78 weeks for the mice or 104 weeks for the rats. Ten mice/sex/group and 10 rats/sex/group were assigned to an interim euthanasia group and were terminated during Weeks 54 and 73, respectively. In addition, 10 mice/sex/group were assigned to a recovery group and did not receive any further exposure following Week 53 but were retained until the core group of animals was euthanized. Transient signs of narcosis were observed for both mice and rats during exposure to 2500 and 5000 ppm and following exposure for mice from the 5000-ppm group. Increased mortality (100% versus 82% for controls) and a decreased mean survival time (577 days versus 631 days for controls) were noted for male rats from the 5000-ppm group. Increases in body weight and/or body weight gain were typically observed for both sexes of mice and rats from the 2500- and 5000-ppm groups throughout the study. Urinalysis and urine chemistry changes indicative of impaired kidney function (i.e., decreased osmolality and increased total protein, volume, and glucose) were noted for male rats from the 2500-ppm group as well as for male and female rats from the 5000-ppm group. At the interim euthanasia, a concentration-related increase in testes weight (absolute and relative as a percentage of body and brain weight) was observed for male rats. Concentration-related increases in absolute and relative liver weight (as a percentage of body weight) were observed for male and female mice. In addition, increased absolute and/or relative (as a percentage of body and brain weight) liver and kidney weights were observed for male and/or female rats from the 2500- and 5000-ppm groups. At necropsy, an increased incidence of seminal vesicle enlargement was observed grossly for male mice from the 2500- and 5000-ppm groups. Microscopically, some of the nonneoplastic lesions noted for mice included an increased incidence of ectasia of the seminal vesicles for male mice from the 2500- and 5000-ppm groups, minimal renal tubular proteinosis for male and female mice from all isopropanol groups, and renal tubular dilation for female mice from the 5000-ppm group. A number of nonneoplastic lesions were observed for male and female rats from the 2500- and 5000-ppm groups, with the most significant lesions being observed in the kidney and associated with chronic renal disease. The lesions noted with increased severity and/or frequency included mineralization, tubular dilation, glomerulosclerosis, interstitial nephritis, interstitial fibrosis, hydronephrosis, and transitional cell hyperplasia. The only tumor type increased in incidence during the study was interstitial cell adenomas of the testes in male rats. However, the increase in these adenomas was not believed to be exposure-related due to an unusually low incidence observed for the control group. There were no increased frequencies of neoplastic lesions noted for male or female mice or for female rats from any isopropanol exposure group. Chronic renal disease was attributed to be the main cause of death for male and female rats from the 5000-ppm group and was also considered to account for much of the mortality observed for male rats from the 2500-ppm group. In conclusion, the no-observed-effect level (NOEL) for toxic effects for both rats and mice was 500 ppm. The NOEL for oncogenicity effects for both mice and rats was determined to be greater than 5000 ppm.

1-Propanol↗
PubMed1997

Characteristics of renal Na(+)-D-glucose cotransport in the skate (Raja erinacea) and shark (Squalus acanthias).

We have investigated the properties of the skate (Raja erinacea) and shark (Squalus acanthias) kidney Na(+)-D-glucose cotransporters (SGLT) in uptake studies of radiolabeled substrates into isolated renal brush-border membrane vesicles (BBMV). Scatchard plot analysis of the substrate dependence revealed that the Na(+)-D-glucose cotransporter population is homogenous within each species. Skate BBMV showed a relatively high affinity for D-glucose [Michaelis constant (K(m)) = 0.12 mM] with an apparent coupling ratio of approximately 2 Na+ to 1 D-glucose, whereas the shark transporter was much lower in affinity (K(m) = 1.90 mM) and had a lower coupling ratio, more like 1 Na+ to 1 D-glucose. These characteristics resemble the properties of SGLT1 and SGLT2, which are known to coexist in the mammalian kidney. Inhibitor studies using sugar analogs and glucosides suggested structural differences of the D-glucose binding site among these transporters, whereas the hydrophobic transporter domains in the vicinity of the D-glucose binding site appeared to be similar. In the high-affinity skate system, D-glucose was recognized by hydrogen bonds to the hydroxy groups at C-2, C-3, and C-4 and by hydrophobic interaction with the C-6 methylene group. In contrast, the low-affinity shark system seemed to lack the hydrophobic recognition motif for the C-6 methylene group of D-glucose.

Animals↗
PubMed1996

Subchronic toxicity of 4-vinylcyclohexene in rats and mice by inhalation exposure.

This study was conducted to evaluate the subchronic toxicity of 4-vinylcyclohexene (VCH). Male and female Sprague-Dawley rats and B6C3F1 mice were exposed by inhalation to VCH 6 hr/day, 5 days/week for 13 weeks. Rats were exposed to 0, 250, 1000, or 1500 ppm, and mice were exposed to 0, 50, 250, or 1000 ppm. In addition, another group of rats and mice was exposed to 1000 ppm butadiene so that a comparison could be made between the two compounds. Exposure to 1000 ppm VCH resulted in deaths of all male mice and 5/10 female mice on Test Days 11 or 12. Three additional female mice exposed to 1000 ppm VCH died prior to study completion. The most notable compound-related clinical sign was lethargy observed in the 1500 ppm VCH-exposed rats and 1000 ppm VCH-exposed mice. Male rats exposed to 1500 ppm VCH had significantly lower body weights compared to controls, and male and female rats in the 1500 ppm group had significantly lower body weight gains. None of the VCH-exposed animals or butadiene-exposed rats showed any compound-related hematological effects. However, mice exposed to 1000 ppm butadiene exhibited mild macrocytic anemia. Clinical chemistry evaluation and urinalysis showed no compound-related effects in rats exposed to either VCH or butadiene. Male and female rats exposed to 1000 or 1500 ppm VCH or 1000 ppm butadiene had increased absolute and/or relative liver weights, and male rats in these same exposure groups had increased relative kidney weights. Microscopically, increased accumulation of hyaline droplets was observed in the kidneys of male rats from all VCH exposure groups. Although compound-related, the droplets were not accompanied by cytotoxicity. In mice, the most notable adverse histopathological effect was ovarian atrophy in females exposed to 1000 ppm VCH or 1000 ppm butadiene. The atrophy was slightly more severe in the VCH-exposed females than in the butadiene-exposed females. There were no other compound-related pathological effects in male or female mice exposed to VCH. Additionally, butadiene-exposed male mice had decreased testicular weights, accompanied by slight testicular degeneration and atrophy. For VCH exposure, the no-observed-adverse-effect-level is 1000 ppm for rats based on lethargy and lowered body weights and 250 ppm for mice based on mortality and ovarian atrophy.

Administration, Inhalation↗
PubMed1996

Variable responses of species and strains to white mineral oils and paraffin waxes.

Recent dietary studies on mineral hydrocarbon (MHC) white oils and waxes have shown inflammatory effects in Fischer 344 (F-344) rats, but not in other rat strains or dogs. Histopathologic effects seen in F-344 rats include mesenteric lymph node histiocytosis, liver granulomas, and inflammation of the mitral valve (only seen with paraffin waxes). Human ingestion of MHC can result in noninflammatory lipogranulomas (oil droplets) in tissues which are regarded as clinically unimportant. It is speculated that inherent interspecies differences in pharmacokinetics and/or immune function may contribute to the differential response to MHC seen in F-344 rats. The F-344 rat retains greater amounts of MHC in target tissues compared to other rat strains and dogs and appears to be more sensitive immunologically to MHC than other species, including humans. This strain may be predisposed to these effects as indicated by a high background incidence of inflammatory granulomatous lesions in control female F-344 rats. Because of its apparently unique sensitivity, relevance of effects seen in F-344 rat to human health is questionable and requires further investigation.

Animals↗
PubMed1996

Isopropanol: summary of TSCA test rule studies and relevance to hazard identification.

The toxicity of isopropanol (IPA) has been extensively studied as a result of a Test Rule under Section 4 of the Toxic Substances Control Act. In general, the data showed that IPA has a low order of acute and chronic toxicity; does not produce adverse effects on reproduction; is neither a teratogen, a selective developmental toxicant, nor a developmental neurotoxicant; and is not genotoxic or an animal carcinogen. IPA is, however, a potential hazard for transient central nervous system depression at high exposure levels. In addition, IPA produced effects to several rodent toxicity endpoints at high dose levels (i.e., motor activity, male mating index, and exacerbated renal disease) which are of unclear relevance to human health. The data generated by these studies confirmed that IPA acts as a typical short-chain alcohol in mammalian biological systems. It produces a significant narcotic effect upon exposure at high levels for extended periods of time, with no irreversible effects even after repeated exposure, which is consistent with other short-chain alcohols. The metabolism of IPA appears equivalent across species with rapid conversion to acetone and carbon dioxide. Overall, these studies demonstrate IPA exposure is a low potential hazard to human health. This information will allow for an improved assessment of the human health risks from IPA exposure.

1-Propanol↗