PubMed Health⌕ Search

Biomedical subjects

T R Tyler

Publications and source records attributed to T R Tyler.

At least 37 records · Page 2Linked to original sources
PubMed1995

A two-generation reproduction study in rats receiving drinking water containing vinyl acetate.

Vinyl acetate (VA) is a commonly used chemical in polymerization and copolymerization processes and as a chemical intermediate. As part of a collaborative effort between VA producers of the United States and British Petroleum, the present study was carried out to provide a base set of data for risk assessment. Groups of male and female Crl:CD(SD)BR rats were given 0, 200, 1000, or 5000 ppm VA via the drinking water over two generations. In addition, a cross-mating trial of control and 5000-ppm male and female rats was conducted in the F1 generation to investigate the slightly decreased litter production in the high-dose group. No treatment-related mortality was observed in any of the groups. Water consumption was significantly reduced in the 5000-ppm groups in both generations and in the 1000-ppm F1 female rats. The body weights of the F0 and F1 male rats and the F1 female rats in the 5000-ppm group tended to be slightly lower than those of the control group. Body weight gain was significantly decreased during lactation in the F0 females at 5000 ppm and in the F1 females at 1000 and 5000 ppm. Pup weights in the F1 generation, but not in the F2 generation, were significantly lower than those of the control on lactation Day 21. The number of litters produced in the F1 generation in the 5000-ppm group was slightly lower than that of the control group and was attributed to lower fertility. Fewer pups were produced when control females were mated with the 5000-ppm males; however, the decrease was due to poor mating performance rather than decreased fertility. No decrease was apparent when the 5000-ppm females were mated with the control group males. Under the conditions of this study, the no-observed adverse effort level was considered to be 1000 ppm.

Administration, Oral↗
PubMed1994

Developmental toxicity evaluation of isopropanol by gavage in rats and rabbits.

Timed-pregnant CD (Sprague-Dawley) rats, 25/group, were dosed orally with aqueous isopropanol (IPA; CAS No. 67-63-0) solutions at 0, 400, 800, or 1200 mg/kg/day, once daily on Gestational Days (GD) 6 through 15 at a dosing volume of 5 ml/kg. Artificially inseminated New Zealand white rabbits, 15/group, were dosed orally with IPA at 0, 120, 240, or 480 mg/kg/day once daily on GD 6 through 18 at 2 ml/kg. Maternal body weights, clinical observations, and food consumption were recorded throughout gestation for both species. At scheduled euthanization for both species (GD 20, rats; GD 30, 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 dams or does aborted, delivered early, or were removed from study. In rats, two dams (8%) died at 1200 mg/kg/day and one dam (4%) died at 800 mg/kg/day. Maternal body weights and weight gain were equivalent across all groups, except for statistically significantly reduced gestational weight gain (GD 0-20; 89.9% of control value), associated with statistically significantly reduced gravid uterine weight at 1200 mg/kg/day (89.2% of control value). There were no treatment-related clinical signs or effects on maternal food consumption. All gestational parameters evaluated were equivalent across groups, including pre- and postimplantation loss, fetal sex ratios, and litter size. Twenty-two to 25 litters were examined per group. Fetal body weights per litter were statistically significantly reduced at the two highest doses (97.3 (n.s.), 94.7, and 94.3% of controls at 800 mg/kg/day and 92.1, 91.9, and 95.4% of controls at 1200 mg/kg/day for all fetuses and males and females separately). No evidence of increased teratogenicity was observed at any dose tested in rats. In rabbits, four does (26.7%) died at 480 mg/kg/day. Maternal body weights were statistically significantly reduced during treatment (GD 6-18) at 480 mg/kg/day (45.4% of control value) with a nonsignificant reduction in gestational weight change (GD 0-30; 77.3% of control value) at this dose. Profound clinical signs of toxicity and statistically significantly reduced maternal food consumption were observed at 480 mg/kg/day. All gestational parameters were equivalent across all doses administered. Thirteen to 15 litters were evaluated per group except for the 480 mg/kg/day group with 11 litters (due to maternal deaths). There were no treatment-related effects on pre- or postimplantation loss, fetal sex ratio, litter size, or fetal body weight/litter. Moreover, no evidence was found of increased teratogenicity at any dose tested in rabbits. Therefore, IPA was not teratogenic to CD rats or to NZW rabbits. The NOAELS for both maternal and developmental toxicity were 400 mg/kg/day in rats, and were 240 and 480 mg/kg/day, respectively, in rabbits.

1-Propanol↗
PubMed1994

Chronic toxicity and oncogenicity study with vinyl acetate in the rat: in utero exposure in drinking water.

The purpose of this study was to evaluate vinyl acetate for potential chronic toxicity and oncogenicity when given to rats in drinking water from the time of gestation. Target concentrations were 0, 200, 1000, and 5000 ppm (v/v). Drinking water solutions were prepared daily and analyzed at approximately 4-week intervals. F0 rats were given solutions of vinyl acetate for 10 weeks and then mated. Offspring (F1 rats) were culled to equal group sizes of 60 main study rats and 30 rats for satellite groups. F1 rats were treated for up to 104 weeks with interim kills of satellite groups at 52 and 78 weeks. Body weights and clinical signs of toxicity were monitored in F0 and F1 rats. Food and water consumption were measured in F1 rats. At Weeks 52 and 78 of the test, clinical pathology and urine analysis examinations were conducted on 10 rats per group from satellite animals. A complete gross and histopathological examination of F1 rats was conducted at the interim kills and on main study rats at Week 104. Average vinyl acetate consumption over the course of the study in male rats of the 200, 1000, and 5000 ppm groups was 10, 47, and 202 mg/kg/day, respectively. Female rats consumed an average of 16, 76, and 302 mg/kg/day, respectively. Compound-related effects observed during the study included a concentration-related decrease in water consumption among rats of the 1000 and 5000 ppm groups and a decrease in food consumption among rats of the 5000 ppm groups. Concurrent body weight decrement was observed only in the 5000 ppm groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1994

Chronic toxicity and oncogenicity inhalation study with vinyl acetate in the rat and mouse.

Vinyl acetate was evaluated for chronic toxicity and oncogenicity in male and female rats and mice in a 104-week study. Target concentrations were 0, 50, 200, and 600 ppm. The study included interim terminations at approximately 53 and 83 weeks and a group whose exposure was terminated at 70 weeks and allowed a 15-week recovery period. Over the course of the exposures, body weight gain was consistently depressed in all 600 ppm groups and in the 200 ppm mice. Except for female rats of the 600 ppm exposure group, recovery animals showed significant improvements in weight gain relative to controls. There were no changes in hematological parameters of either species that could be unequivocally related to treatment. The only effect noted on clinical chemical parameters during the study were decreases in blood glucose in the 600 ppm females. There were no adverse effects on survival in either species. Increases in lung weight were noted in rats and mice primarily in the 600 ppm groups. These changes were associated with bronchial exfoliation, macrophage accumulation, and fibrous plaques and buds extending into the airway lumen, and bronchial/bronchiolar epithelial disorganization. The most significant histopathological changes were noted in the nasal cavity. In the olfactory epithelium of both rats and mice, the main nonneoplastic changes included epithelial atrophy, regenerative effects (squamous metaplasia and respiratory metaplasia of olfactory epithelium), basal cell hyperplasia, and epithelial nest-like infolds. No nonneoplastic changes were observed in the respiratory epithelium of rats, while squamous metaplasia at the naso/maxilloturbinate region was prevalent in mice. Nonneoplastic changes were similar in the recovery groups. Oncogenic responses to vinyl acetate exposure were mainly confined to the nasal cavity in rats and included endo- and exophytic papillomas, squamous cell carcinoma, carcinoma in situ in olfactory regions, and endophytic papilloma in respiratory regions. Squamous cell carcinomas were also found either in areas normally covered by cuboidal epithelium or areas of unknown origin. One squamous cell carcinoma was found in the larynx of a rat of the 600 ppm groups. One squamous cell carcinoma was found in the lung of a mouse of the 600 ppm group.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Inhalation↗
PubMed1994

Disposition and pharmacokinetics of isopropanol in F-344 rats and B6C3F1 mice.

The absorption, metabolism, disposition, and excretion of isopropanol (IPA) were studied in male and female rats and mice. Animals were exposed by i.v. (300 mg/kg) and inhalation (500 and 5000 ppm for 6 hr) routes; additionally, IPA was given by gavage to rats only in single and multiple 300 and 3000 mg/kg doses. In the rat approximately 81-89% of the administered dose was exhaled (as acetone, CO2, and unmetabolized IPA); approximately 76% of the dose in mice was exhaled after i.v. bolus but 92% was exhaled following inhalation. Approximately 3-8% of the administered dose was excreted in urine as IPA, acetone, and a metabolite tentatively identified as isopropyl glucuronic acid. Small amounts of radiolabel were found in feces and in the carcass. There were no major differences in the rates or routes of excretion observed either between sexes or between routes of administration. Additionally, repeated exposure had no effect on excretion. However, both the route of administration and the exposure or dose level influenced the form in which material was exhaled. Following exposure to 5000 ppm, a greater percentage of unmetabolized IPA was recovered in the expired air than following exposure to 500 ppm, implying saturation of metabolism.

1-Propanol↗
PubMed1994

Isopropanol 13-week vapor inhalation study in rats and mice with neurotoxicity evaluation in rats.

This study was conducted to evaluate the possible subchronic toxicity as well as neurobehavioral effects of isopropanol, a widely used industrial and commercial solvent. Five groups, each containing 10 Fischer 344 rats/sex and 10 CD-1 mice/sex, were exposed for 6 hr/day, 5 days/week, for 13 weeks to isopropanol vapor at concentrations of 0 (control), 100, 500, 1500, or 5000 ppm. An additional 15 rats/sex were assigned to the 0, 500, 1500, and 5000 ppm groups for assessment of neurobehavioral function. No exposure-related mortalities occurred during the study. The narcotic effects of isopropanol were noted only during exposures at 1500 and 5000 ppm. These signs, noted during exposures, were typically absent following exposures. The only clinical signs observed following exposures included swollen periocular tissue, perinasal encrustation, and ataxia for rats of the 5000 ppm group. Neurobehavioral evaluations indicated no changes in any of the parameters of the functional observational battery; however, increased motor activity for female rats in the 5000 ppm group was noted at Weeks 9 and 13. Decreases in body weight and body weight gain were observed for rats of the 5000 ppm group at the end of the first week of exposure. During the remaining weeks, increases in body weight and/or body weight gain were observed for rats of the 1500 and 5000 ppm groups. No exposure-related effects on body weight were noted for male mice; however, increased body weight and body weight gain were observed for female mice of the 5000 ppm group.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Propanol↗
PubMed1993

In vitro and in vivo assays of isopropanol for mutagenicity.

To assess the mutagenic potential of isopropanol, an in vitro Chinese hamster ovary (CHO) cell/HGPRT gene mutation assay and a bone marrow micronucleus study in mice were conducted. In the CHO/HGPRT assay, concentration levels ranged from 0.5 to 5.0 mg/ml. No elevated mutant frequencies attributable to treatment were observed in the test under either activated or non-activated conditions. In the micronucleus assay, mice were injected intraperitoneally (IP) with either 350, 1,173, or 2,500 mg/kg of isopropanol at constant volumes of 10 ml/kg. No increased incidence of micronuclei was observed in bone marrow polychromatic erythrocytes (PCEs) harvested at 24, 48, or 72 hr post-dosing. In both assays, negative and positive control mutant frequencies were within historical control ranges. These results, in conjunction with previously published data, clearly demonstrate that isopropanol is not a mutagen.

1-Propanol↗
PubMed1992

The developmental toxicity of 2-ethylhexanol applied dermally to pregnant Fischer 344 rats.

Undiluted 2-ethylhexanol (2-EH) was administered by occluded dermal application for 6 hr per day on Gestation Days 6 through 15 to pregnant Fischer 344 rats, in range-finding (R) and main (M) studies. The dermal route is considered to be the most relevant for human exposure. Treatment levels were (R) 0.0, 0.5, 1.0, 2.0, and 3.0 ml/kg/day (equivalent to 0, 420, 840, 1680, and 2520 mg/kg/day) and (M) 0.0, 0.3, 1.0, and 3.0 ml/kg/day (equivalent to 0, 252, 840, and 2520 mg/kg/day). Controls (0.0 ml/kg/day, sham controls) received deionized water at 3.0 ml/kg/day. Dermal-positive control groups received undiluted 2-methoxyethanol (2-ME) at (R) 0.5 and 1.5 ml/kg/day and (M) 1.0 ml/kg/day as a reference compound in a similar regimen. An oral reference compound, valproic acid, was administered by gavage in the range-finding study on Gestation Days 6 through 15 at 400 mg/kg/day. The range-finding study employed an untreated (naive) control group. Numbers of plug-positive females per group were (R) 8 and (M) 25. Maternal weight gain was reduced for 2-EH at 1680 (R) and 2520 (R and M studies) mg/kg/day. Exfoliation and encrustation were seen at the application site in both studies at 840, 1680, and 2520 mg/kg. Maternal liver, kidney, thymus, spleen, adrenal, and uterine weights, and gestational and fetal parameters were unaffected by treatment with 2-EH. There were no treatment-related increases in the incidence of individual or pooled external, visceral, and skeletal malformations or variations following the application of 2-EH. The NOAELs for the maternal toxicity of 2-EH were 252 mg/kg/day based on skin irritation and 840 mg/kg/day based on systemic toxicity. The developmental toxicity NOAEL was at least 2520 mg/kg/day, with no teratogenicity. Administration of 2-ME at 840 mg/kg/day resulted in reduced maternal weight gain and food consumption, increased postimplantation loss, reduced numbers of live fetuses per litter, and reduced fetal body weights per litter. The incidence of fetal malformations and variations was increased. Oral administration of VPA produced maternal toxicity, developmental toxicity, and teratogenicity. The Fischer 344 rat is thus susceptible to known rodent teratogens by both the dermal and oral routes. It is concluded that 2-EH is not developmentally toxic by the dermal route in the Fischer 344 rat at and below treatment levels which produce maternal toxicity.

Administration, Cutaneous↗
PubMed1992

Two-week aerosol inhalation study in rats of ethylene oxide/propylene oxide copolymers.

Previous studies have shown that aerosols of an ethylene oxide/propylene oxide copolymer (UCON 50-HB-5100) produced an inflammatory response in lungs of rats in short-term repeated exposures at relatively low concentrations. This study was carried out on related polyalkylene glycols (EO/PO copolymers) to determine if similar effects would occur upon short-term repeated exposure. Rats were treated by whole body liquid droplet aerosol exposures of six hours per day, five days per week for two consecutive weeks to each of five EO/PO copolymers. The exposure level for the positive control (UCON 50-HB-5100) was 55 mg/m3, while the remaining 4 test copolymers were evaluated at 100 mg/m3. Each exposure group consisted of ten male albino rats. After three exposures, nine of ten rats exposed to UCON 50-HB-5100, and six of ten rats exposed to UCON 50-HB-2000 had died. At necropsy, congestion, consolidation and red discoloration of the lungs were noted. A moderate to severe alveolitis, characterized by intraalveolar edema, hemorrhage and fibrin deposition, was observed after five days of exposure. At necropsy, these rats exhibited elevated lung weights and similar macroscopic and microscopic lesions. Rats exposed to the other test materials (UCON 75-H-1400, Pluronic L17R1, Pluronic L31, and Pluronic L64) survived with essentially no signs of toxicity through the ten exposure days. Body weights, organ weights, hematological evaluation, pharmacotoxic signs, and macroscopic and microscopic evaluation after necropsy were similar between groups and when compared to the negative control group. Only a slight alveolitis was noted after two weeks of exposure which subsided by two-weeks post exposure.

Administration, Inhalation↗
PubMed1991

Aging and attitude change.

Social psychologists have proposed a variety of different models to account for people's relative openness to attitude change through the life cycle. Two of the most important models are the impressionable years model, which suggests an especially great openness to change among the young, and the lifelong openness model, which suggests that age is unrelated to openness to attitude change. Two studies were conducted to examine the openness of people of varying ages to attitude change. In both studies, the influence of personal experiences with government agencies on attitudes toward government was examined. The attitudes of older people changed as much or more in response to their personal experiences as did those of younger people. These results support the lifelong openness model of attitude change.

Adolescent↗
PubMed1989

Two-week aerosol inhalation study on polyethylene glycol (PEG) 3350 in F-344 rats.

PEGs in the 3000 to 4000 MW range are used in many pharmaceutical and cosmetic applications; they produce little ocular or dermal irritation and have extremely low acute and subchronic toxicity by oral and dermal routes of administration. However, little information exists on the potential of aerosols of these materials to produce adverse health effects. F-344 rats were exposed to aerosols of PEG 3350 (20% w:w in water) at 0, 109, 567, or 1008 (highest attainable) mg/m3 for 6 hr/d, 5 d/wk for 2 wk. No exposure-related toxicity was found with regard to clinical signs, ophthalmology, serum chemistry, urinalysis, or gross pathology. Exposure-related effects included: a 50% increase in the neutrophil count (males only) at 1008 mg/m3; decreased body weight gain (16%) for both the 567 and 1008 mg/m3 groups (males only); absolute lung weights of both sexes were increased 10 and 18% for the 567 and 1008 mg/m3 groups, respectively. A slight increase in the number of macrophages in the alveoli was the only change observed histologically in all PEG 3350-exposed groups. Therefore, inhalation of aerosols of PEG 3350 at concentrations up to 1008 mg/m3 produced relatively little toxicity in rats, the lung was the target organ, and the no-observable-effect-level was between 109 to 567 mg/m3.

Aerosols↗
PubMed1988

Pulmonary fibrosis produced in F-344 rats by subchronic inhalation of aerosols of a 4000 molecular weight ethylene oxide/propylene oxide polymer.

Inhalation of aerosols of the ethylene oxide/propylene oxide polymer (U-5100) evaluated in this study has previously been shown in acute and 2-week studies to produce toxicologic effects on the lungs, with increased lung weights and microscopic findings of congestion and hemorrhage of pulmonary alveolar capillaries and necrosis of alveolar epithelial cells (D. R. Klonne, D.J. Nachreiner, D. E. Dodd, P. E. Losco, and T.R. Tyler, 1987, Fundam. Appl. Toxicol. 9, 773-784). In the present studies, F-344 rats were exposed 6 hr/day, 5 day/week for 2 weeks to aerosols at mean concentrations of 0, 0.9, or 5.0 mg/m3 or for 13 weeks to mean concentrations of 0, 0.3, 1.1, or 5.2 mg/m3. Following the 2-week study, minimal multifocal hemorrhage and eosinophilic proteinaceous debris in alveoli were observed in the 0.9 mg/m3 group; similar lesions plus alveolar cell necrosis were found in the 5 mg/m3 group. In the 13-week study, the 5.2 mg/m3 group had a slight decrease in body weight gain, while increases in absolute and/or relative lung weights occurred for both the 1.1 and 5.2 mg/m3 groups at the end of the exposure regimen and at the end of a 5-week recovery period. Histologic lesions of the lungs occurred in all U-5100-exposed groups and consisted of hemorrhage, alveolar histocytosis, interstitial pneumonia, and multifocal fibrosis. The incidence and severity of the pulmonary lesions were concentration related.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1988

Developmental toxicity evaluation of inhaled 2-ethoxyethanol acetate in Fischer 344 rats and New Zealand white rabbits.

Pregnant Fischer 344 rats and New Zealand white rabbits were exposed to 2-ethoxyethanol acetate (EEA; CAS No. 111-15-9) vapor by inhalation on Gestational Days 6 through 15 (rats) or 6 through 18 (rabbits) at concentrations of 0, 50, 100, 200, or 300 ppm, 6 hr/day. The animals were terminated on Gestational Day 21 (rats) or 29 (rabbits) and fetuses were examined for external, visceral, and skeletal malformations and variations. In rabbits, exposure to 100-300 ppm resulted in maternal toxicity: decreased weight gain at 100-300 ppm, clinical signs at 200-300 ppm, alterations in hematology at 100-300 ppm, reduced gravid uterine weight at termination at 200-300 ppm, and elevated absolute liver weight at 300 ppm. Developmental toxicity was observed at 100-300 ppm: an increased incidence of totally resorbed litters at 200-300 ppm, an increase in nonviable fetuses at 300 ppm, and a decrease in viable implants (live fetuses) per litter at 200-300 ppm. The incidence of fetal malformations (external, visceral, and skeletal) was increased at 200-300 ppm. The incidence of total malformations was 100% at 300 ppm and significantly increased at 200 ppm. Reduced fetal ossification was observed at 100-300 ppm. In rats, exposure to 100-300 ppm also resulted in maternal toxicity: reduced weight gain and reduced food consumption at 200-300 ppm and elevated relative liver weight and alterations in hematology at 100-300 ppm. Absolute maternal liver weight was increased at all EEA exposure concentrations; relative liver weight was increased at 100-300 ppm. Developmental toxicity was observed at 100-300 ppm: increased nonviable implantations/litter (300 ppm), reduced fetal body weight/litter (200-300 ppm), and increased incidence of external (300 ppm), visceral, and skeletal (100-300 ppm) variations indicative of toxicity. The incidence of visceral, skeletal, and total malformations was increased at 200-300 ppm. In conclusion, in both species, inhalation exposure to EEA during organogenesis produced maternal toxicity at 100-300 ppm and developmental toxicity at 100-300 ppm, including teratogenicity at 200-300 ppm. At 50 ppm in both species, there was no evidence of maternal or developmental toxicity, including teratogenicity.

Administration, Inhalation↗
PubMed1987

Developmental toxicity evaluation of inhaled methyl isobutyl ketone in Fischer 344 rats and CD-1 mice.

Pregnant Fischer 344 rats and CD-1 mice were exposed to methyl isobutyl ketone vapor (CAS No. 108-10-1) by inhalation on Gestational Days 6 through 15 at concentrations of 0, 300, 1000, or 3000 ppm (mean analytical values of 0, 305, 1012, and 2997 ppm, respectively). The animals were sacrificed on Gestational Day 21 (rats) or 18 (mice), and live fetuses were examined for external, visceral, and skeletal alterations. In rats, exposure to 3000 ppm resulted in maternal toxicity expressed as clinical signs, decreased body weight and body weight gain, increased relative kidney weight, and decreased food consumption, and in fetotoxicity expressed as reduced fetal body weight per litter and reductions in skeletal ossification. In mice, exposure to 3000 ppm resulted in maternal toxicity expressed as exposure-related increases in deaths (12.0%, 3/25 dams), clinical signs, and increased absolute and relative liver weight, and in fetotoxicity expressed as increased incidence of dead fetuses, reduced fetal body weight per litter, and reductions in skeletal ossification. No treatment-related increases in embryotoxicity or fetal malformations were seen in either species at any exposure concentration tested. There was no evidence of treatment-related maternal, embryo, or fetal toxicity (including malformations) at 1000 or 300 ppm in either species.

Administration, Inhalation↗
PubMed1987

Acute and 2-week inhalation toxicity studies on aerosols of selected ethylene oxide/propylene oxide polymers in rats.

The ethylene oxide/propylene oxide (EO/PO) polymers evaluated in this study have previously been shown to have a low order of toxicity and/or irritancy by ocular, dermal, or oral routes of administration. These studies evaluated the acute inhalation toxicity of respirable aerosols of three EO/PO compounds (U-660, U-2000, and U-5100) that differ in chain length, molecular weight, and viscosity. The respective 4-hr LC50 values (95% confidence limits) for U-660, U-2000, and U-5100 in Wistar albino rats were 4670 (4090-5320), 330 (227-480), and 106 (45-245) mg/m3. Occasionally, slight increases in respiration rate and slight hyperactivity were observed during the postexposure period. All deaths were delayed for 2-5 days postexposure. Body weight gains were transiently depressed in rats exposed to U-2000 and U-5100. Discolored lungs and livers occurred in animals which died during the 14-day postexposure period. Subsequently, a repeated-exposure study was conducted on U-5100 in F-344 rats exposed for 6 hr/day, 5 days/week, for 9 exposures at mean concentrations of 0, 5, 26, and 50 mg/m3. Portions of the control and 50 mg/m3 groups were maintained for an additional 2-week recovery period. Exposure-related effects included transient urogenital wetness in 50 mg/m3 group females; decreased body weight gain (7-29%) in all U-5100 groups except the 5 mg/m3 group females; increases in absolute (17-52%) and relative lung weights in all U-5100 groups; macroscopic red foci in the lungs; and microscopic findings of congestion and hemorrhage of pulmonary alveolar capillaries and necrosis of alveolar epithelial cells. Lung weights remained elevated after the 2-week recovery period, but the severity of the microscopic lesions was noticeably less, indicating partial reversibility of the lesions. In conclusion, EO/PO polymers have a higher order of toxicity by inhalation in comparison to other routes of administration, vary considerably in their acute lethal toxicity as a function of chain length/molecular weight, and induce pulmonary hemorrhage, and possibly edema, following repeated aerosol exposures at concentrations as low as 5 mg/m3.

Aerosols↗
PubMed1987

Hyalin droplet nephrosis in male Fischer-344 rats following inhalation of diisobutyl ketone.

Four groups, each consisting of 10 male and 10 female Fischer-344 rats, were exposed 6 h/day, 5 days/week, for 9 days to diisobutyl ketone (DIBK) vapor at concentrations of 905, 300, 98, or 0 (control) ppm. An additional 10 rats/sex were assigned to the 905 and 0 ppm groups and allowed two weeks recovery prior to sacrifice. Rats exposed to 905 ppm had mild ocular irritation (lacrimation) and evidence of kidney toxicity, manifested as: 1) an increase in absolute and relative (as a percentage of body weight) kidney weights, 2) an increase in urine volume (and water intake) with a concomitant decrease in urine osmolality (males only), and 3) an increase in severity of hyalin droplet nephrosis in the proximal tubules (males only). Absolute and relative liver weights were also increased in both male and female rats of the 905 and 300 ppm groups. These effects either disappeared or lessened in severity following the 2-week recovery period. Male rats exposed to 300 ppm had similar renal alterations to the males of the 905 ppm group, although the alterations were fewer in number and smaller in magnitude. Kidney weights and renal histology of the males of the 98 ppm group were similar to the control male rats, although an increase in urine volume with a decrease in urine osmolality was observed. The kidney findings in this study were not surprising because of the chemical relationship of DIBK with other aliphatic ketones (e.g., methyl isobutyl ketone, methyl isoamyl ketone) which, after repeated inhalation exposure, cause hyalin droplet nephropathy in male rats. The significance of this male rat nephrosis with regard to human exposure is unknown.

Administration, Inhalation↗
PubMed1986

The sensitizing potential of primary amyl acetate in the guinea pig.

Primary amyl acetate is a liquid mixture of the isomeric forms of pentyl acetate, which is used as a volatile organic solvent. Because of the possibility for skin contact, primary amyl acetate was investigated for its potential to cause allergic contact dermatitis. Using a guinea pig maximization procedure, primary amyl acetate was found to be a possible marginal skin sensitizer.

Animals↗