摘要:

The filter model was used to estimate thresholds for the induction of cancer from many dose‐response sets for inhalation and ingestion exposure to vinyl chloride for rat and inhalation exposure for mouse. Estimates for a variety of end‐point combinations were log‐normally distributed over about 2 decades from about 1 to 100 ppm for inhalation exposure to rat and 0.1 to 30 ppm for mouse. When the data is transformed to “dose” (milligrams per kilogram body weight per day), the estimates for inhalation and ingestion exposure and also for rat and mouse are similar. Estimates for different experiments carried out for different durations of time (single exposure to 1 yr) are comparable. Since the threshold is an intrinsic property of the biological system, the estimate, even from a protocol for short exposure and less than lifetime observation, can be used directly in a risk assessment as the maximum safe dose.

ISSN:0098-4108    

DOI:10.1080/15287398609530798

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

An inverse correlation between the concentration of DDE in human breast milk samples and the duration of breast feeding prompted the present study of the effects of DDE administration on the lactational performance of primiparous rats. Daily doses of 10 mg p,p'‐DDE/kg body weight were given to virgin female Sprague‐Dawley rats 5 d/wk for 5 wk prior to mating and continued throughout the gestation and lactation periods. Lactation capacity was determined by monitoring neonatal growth and by measuring milk production, milk composition (total protein, total lipid, and lactose), and mammary‐gland weight and nucleic acid content on d9 and 20 postpartum. Cross toxicity was assessed by monitoring clinical signs and body weight of the dams, and by measuring organ weights of the dams on lactation d 9 and 20. Histopathological evaluation of the mammary glands and selected organs in the dams and pups was also performed. The dose level of DDE employed was apparently not toxic to the dams and did not have a pronounced effect on neonatal mortality. No significant differences between DDE‐treated and control groups were observed for any of the lactation parameters, even though the concentration of DDE in the milk of treated rats was approximately two orders of magnitude greater than the upper range of the DDE levels measured in human milk samples. These findings indicate that DDE does not adversely affect lactation or neonatal growth in Sprague‐Dawley rats at the dose level used in this study.

ISSN:0098-4108    

DOI:10.1080/15287398609530799

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The disposition of [14C]‐2‐bromo‐4,6‐dinitroaniline (BDNA) was studied in male F344 rats following oral or intravenous (iv) administration. The gastrointestinal absorption of BDNA was nearly complete and was not affected by dose in the range (10–100 μmol/kg body weight) studied. Following either oral or iv administration, BDNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue. Clearance of [14C]BDNA‐derived radioactivity from various tissues was rapid and was best described by two‐component decay curves. The whole‐body half‐life of BDNA was approximately 7 h. Within 72 h, clearance of [14C]BDNA‐derived radioactivity from the body was 98% complete. [14C]BDNA was rapidly cleared by metabolism to 13 metabolites, which were excreted in urine (62%) and feces (33%). Most (66%,) of the urinary radioactivity was excreted in the form of sulfate conjugates of two metabolites of BDNA; excretion of unmetabolized BDNA was minimal (less than 2%J. Biliary excretion of [14C]BDNA was significant; however, some of this BDNA‐derived radioactivity underwent enterohepatic circulation and was subsequently excreted in urine. Results of this study indicate that, if metabolism is a detoxification process, the rapid metabolism and excretion of this compound should minimize the likelihood of chronic toxicity from repeated exposure to BDNA beyond that predicted by data from acute or short‐term exposures.

ISSN:0098-4108    

DOI:10.1080/15287398609530800

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The effects of orally administered benzyl chloride (BCI) on fetal development were evaluated in the rat. Doses of BCI at 0, 50, or 100 mg/kg in corn oil were given daily on 6–15 of gestation. No toxic symptoms were observed following exposure of pregnant rats to BCI. Fetotoxicity in the form of reduced fetal length was observed when dams were treated with BCI at 100 mg/kg. Benzyl chloride did not statistically increase the number of skeletal and visceral variations.

ISSN:0098-4108    

DOI:10.1080/15287398609530801

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

The inhalation of cotton dust by cotton‐mill workers causes byssinosis, a disease characterized by chest tightness and other symptoms indicative of bronchoconstric‐tion. In the present study the dog isolated trachealis smooth muscle preparation was employed to examine the ability of a crude, water extract of cotton bracts (CBE) to (1) cause contractile responses mediated by receptors, (2) modify responses of the tissue to a number of excitatory and inhibitory agents, and (3) alter responsiveness of the preparations to electrical field stimulation mediated by intrinsic cholinergic, excitatory nerves and adrenergic, inhibitory nerves. CBE evoked contraction of the tissues by an action that did not involve muscarinic, histamine, or 5‐hydroxytrypta‐mine receptors. The maximum tissue responses to exogenous histamine, 5‐hydroxy‐tryptamine, and isoproterenol were enhanced significantly in the presence of CBE, while those to KCI and methacholine were unaffected. The sensitivities (EC50 values) of the tissues to these agents were not, however, altered by CBE. Contractions induced by cholinergic nerve stimulation were increased in the presence of CBE, via a mechanism that appears, at present, to result from a prejunctional facilitation of acetycholine release. Relaxations to adrenergic nerve stimulation were not affected by CBE. Results suggest that, in addition to its direct, contractile activity, CBE can alter indirectly the responsiveness of the tissue to a number of endogenous mediator substances. Intrinsic, cholinergic excitatory nerves may be a target for the acute action of CBE as well.

ISSN:0098-4108    

DOI:10.1080/15287398609530802

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

In a group of control subjects, the mean serum angiotensin‐converting enzyme (ACE) level was 38.1 ± 10.6 nmol/min • ml (n = 30), and in a group of silicosis patients the mean serum ACE level was 45.2 ± 76.0 (n = 26). Thirteen of these patients were classified as having nodular silicosis, and their mean serum ACE level was 44.2; 10 of these patients were classified as having progressive massive fibrosis, and their mean serum ACE level was 39.4. Three of these patients had confirmed silicotuberculosis, and their serum ACE levels were 63, 67, and 77 (mean = 69) these serum ACE levels are somewhat higher than those having been reported for patients with acute sarcoid‐osis. Thus, when serum ACE levels are being used to assist in distinguishing between silicosis and sarcoidosis, the possibility of silicotuberculosis must be also considered when high serum ACE levels are encountered.

ISSN:0098-4108    

DOI:10.1080/15287398609530803

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Monoalkyl dithiocarbamates are capable of mobilizing cadmium from aged intracellular deposits in which the cadmium is largely present in metallothionein. The sodium salts of monomethyl, ethyl, n‐propyl, and n‐butyl dithiocarbamates have been prepared, characterized, and examined for their relative ability to mobilize cadmium from such aged deposits in the kidneys, liver, spleen, testes, brain, and pancreas as well as from the whole body, using sodium diethyl dithiocarbamate as the positive control. Alterations in the structure of the dithiocarbamates can be correlated with alterations in organ cadmium levels. The acute toxicity of these compounds is sufficiently greater than disubstituted dithiocarbamates that their use would appear to possess few advantages, although they do seem to be more effective in reducing testicular cadmium levels.

ISSN:0098-4108    

DOI:10.1080/15287398609530804

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Sunflowers were grown on soil amended with 224 metric tons/ha of municipal sewage sludge from Syracuse, N.Y. The yield of sunflower seeds was reduced by 47.2% by the sludge addition. The harvested seeds contained 1.71 ppm dry weight of cadmium. Deoiled seed meal was incorporated as 25 and 50% of semipurified diet and fed to male and female Japanese quail. The concentrations of cadmium were higher in kidney, liver, muscle, and eggs of birds fed the sludge‐grown seed meal as compared to control quail. Tissue concentrations of cadmium increased with increasing dietary levels of sludge‐grown seed meal. No significant differences (p> 0.05) were observed between dietary treatments in the activity of hepatic microsomal p‐nitroanisole O‐demethylase or aminopyrineN‐demethylase in the male birds. Additionally, no mu‐tagenic activity, either direct or with metabolic activation, was found in quail eggs. No observable changes in tissue ultrastructure were observed under electron microscopy in any of the treatment groups. There were no significant (p> 0.05) differences among the dietary treatment groups in feed intake, growth rate, egg production, or egg hatchability.

ISSN:0098-4108    

DOI:10.1080/15287398609530805

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

Paniculate Ni5As2has been shown to be highly cytotoxic and carcinogenic. By measuring the solubility of Ni5As2particles in a variety of aqueous solutions, we have determined that particulate Ni5As2that might be produced during oil‐shale retorting could be mobilized to the environment and made available to the cells of living organisms, including humans. Ni5As2was five times more soluble in ground water taken from aquifers surrounding a major oil‐shale source in Colorado, U.S.A., than in distilled water. It was also two times more soluble in oil‐shale product water from an above‐ground retort than in distilled water. Thus, it is possible that Ni5As2could be solubilized and mobilized to the environment by the flooding of abandoned in situ retorts with ground water or by the disposal of oil‐shale product water by spraying it on spent shale beds. Particulate Ni5As2was found to be 12 times more soluble in culture growth medium than in distilled water, and much more soluble in solutions of amino acids, inorganic salts, organic constituents of culture medium, and 75% calf serum. These observations suggest Ni5As2particles in airborne dust would be dissolved when they came in contact with the biological fluids of the lung and gastrointestinal tract. The availability to cells of the soluble products of NisAs2was demonstrated by measuring its effects on cell proliferation. As little as 1 ppm soluble NisAs2retarded Chinese hamster (CHO) cell proliferation in culture, and 4 ppm resulted in cell death. Flow cytometry measurements indicated there was a preferential cytotoxic effect on S‐phase cells. Despite this, many cells survived to form colonies, causing concern that Ni5As2might cause genetic damage that could be passed on to future cell generations. This did not appear to be the case, however, for no mutations could be detected at the hypoxanthine‐guanine phosphoribosyl transferase (HCPRT) locus in cells that survived the cytotoxic effects. This suggests that Ni5As2carcinogenesis might be caused by epigenetic rather than mutagenic mechanisms.

ISSN:0098-4108    

DOI:10.1080/15287398609530806

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor

摘要:

DNA replication in Chinese hamster lung fibroblasts, line V79, was depressed in a dose‐dependent manner over an ozone concentration range of 1–10 ppm. When the cells were exposed for 1 h at concentrations up to 6 ppm, the rate of DNA replication, as measured by [3H]thymidine incorporation, declined further during a 3‐h period immediately following exposure. At higher ozone concentrations, at which more than 99.9% of the cells were killed, no further decline in DNA replication was seen beyond that immediately following exposure. Cultures exposed for 1 h to 10 mM ethyl meth‐anesulfonate or to 10J/m2of ultraviolet (UV) light showed a similar progressive decline in the rate of DNA replication. The inhibition of DNA replication by ozone resembled that seen after exposure of cells to chemical mutagens or radiation and did not resemble the inhibition produced by metabolic poisons. The results may indicate that ozone or its reaction products interact directly with DNA in a way that inhibits replication.

ISSN:0098-4108    

DOI:10.1080/15287398609530807

出版商:Taylor & Francis Group    

年代:1986

数据来源: Taylor