摘要:

It is well established that certain metals are toxic to embryonic and fetal tissues and can induce teratogenicity in mammals. The main objective of this paper has been to summarize the toxic effects that excesses of certain metals may cause on mammalian development. The reviewed elements have been divided into four groups: (a) metals of greatest toxicological significance (arsenic, cadmium, lead, mercury, and uranium) that are widespread in the human environment, (b) essential trace metals (chromium, cobalt, manganese, selenium, and zinc), (c) other metals with evident biological interest (nickel and vanadium), and (d) metals of pharmacological interest (aluminum, gallium, and lithium). A summary of the therapeutic use of chelaling agents in the prevention of metal‐induced developmental toxicity has also been included. meso‐2,3‐Dimercaptosuccinic acid (DMSA) and sodium 2,3‐dimercaptopropane‐1‐sulfonate (DMPS) have been reported to be effective in alleviating arsenic‐ and mercury‐induced teratogenesis, whereas sodium 4,5‐dihydroxybenzene‐1,3‐disulfonate (Tiron) would protect against vanadium‐ and uranium‐induced developmental toxicity.

ISSN:0098-4108    

DOI:10.1080/15287399409531868

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

The objective of this study was to examine the immunotoxicological effects of the methyl‐carbamate pesticide carbaryl via the oral, dermal, or inhalation routes. Male CD rats were exposed to carbaryl 5 d/wk for a 2‐wk period. During nose‐only inhalation exposures, rats received either 36, 137, or 335 mg/m3carbaryl in acetone for 6 h. Air only and acetone/air controls were run concurrently. Orally exposed animals received either 1 ml corn oil or 10, 25, or 50 mg/kg carbaryl, while dermally exposed animals received either 2 ml acetone or 100, 500, or 1000 mg/kg carbaryl on their dorsal flank for 6 h. Four days prior to sacrifice, animals from all exposure groups were injected iv with 2 × 108sheep red blood cells (SRBC). The primary immunoglobulin M (IgM) humoral immune response to SRBC was then assessed by measuring SRBC‐specific antibody‐forming cells (AFC) and levels of serum anti‐SR.BC IgM antibody, respectively, using the hemolytic plaque assay and an enzyme‐linked immunosorbent assay. Individual body weights, spleen, thymus, and liver weights, spleen cell number, and red and white blood cell (RBC, WBC) counts were obtained for each animal. Following nose‐only inhalation exposures, dose‐dependent decreases in thymus weights, spleen cell number, AFC/spleen, AFC/106splenocytes, and serum levels of SRBC‐specific IgM antibody were observed. Significant decreases of 33, 57, and 22% in spleen cell number, AFC/spleen, and thymus weight, respectively, were found at the 335 mg/m3exposure level. Animals exposed orally to 25 mg/kg carbaryl had a 34% decrease in WBC counts. A 34% decrease in WBC and a 13% increase in RBC counts were observed at the 50 mg/kg oral dose. Significant decreases in liver weights ranging from 11 to 13% were found at all oral exposure levels. Dermal exposure to carbaryl revealed no significant toxicological effects. Results indicate that humoral immune suppression was observed following inhalation, but not following oral or dermal exposures to carbaryl. Immunotoxicological studies evaluating pesticides need to consider relevant exposure routes and dosages for appropriate risk assessment procedures and exposure limits to be established.

ISSN:0098-4108    

DOI:10.1080/15287399409531869

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Human milk samples from 28 mothers at Oslo City Hospital, Norway, were collected in 1991 and analyzed for individual polychlorinated biphenyl (PCB) congeners, IUPAC numbers 28, 74, 99, 101, 105, 114, 118, 128, 138, 141, 153, 156, 157, 170, 180, 194, and 206, plus selected non‐ortho‐substituted compounds, IUPAC numbers 77, 126, and 169. Sum DDJs (sum of concentrations of DDT and related compounds), hexachlorobenzene (HCB), oxychlordane, transnonachlor, and sum hexachlorocyclohexanes (HCHs) (sum of concentrations of α‐HCH, β‐HCH, and y‐HCH) were also determined. The mean levels of sum DDTs, HCB, oxychlordane, transnonachlor, and sum HCHs were 338, 41, 9, 19, and 36 nglg, respectively, in human milk fat. p,p'‐DDE and β‐HCH accounted for 81 and 93% of sum DDTs and sum HCHs, respectively. The mean level of sum PCBs (sum of mean concentrations of 20 individual congeners) was 372 nglg milk fat. A very good correlation was found between sum PCBs and PCB‐153 (r = .97). Sum PCBs determined on a capillary column was found to account for 62–79% of total PCBs calculated by using the packed column method used in previous human milk surveys in Norway. Comparison with previous results revealed that the mean sum PCB, HCB and sum DDT levels were decreased by 70, 65, and 75%, respectively during the past 9 yr. The contribution of individual PCDDIPCDF (earlier Norwegian study) and non‐ and mono‐ortho‐substituted PCB congeners to the total calculated toxic equivalent values was assessed, and the PCBs were found to constitute a major part of the TCDD equivalents in human milk, with PCB‐126 as the main contributor.

ISSN:0098-4108    

DOI:10.1080/15287399409531870

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

Male Wistar rats were injected ip with 0 or 20 mg/kg 3,3′,4,4′,5,5′‐hexabromobiphenyl and blood samples were collected 1, 3, 6, 7, and 8 d later. At 8 d after the injection, serum retinol was increased 30% and serum thyroxine was decreased 26% relative to control values. These effects were apparently unrelated to transthyretin in that the biphenyl did not alter the proportion of thyroxine binding in vitro to the prealbumin fraction of serum proteins. Separate groups of control and HBBP‐injected rats did not receive food on d 7 (i.e., 24‐h fast) and d 8 after injection (i.e., 48‐h fast), fasting decreased the serum retinol and thyroxine concentrations as well as the proportion of thyroxine binding in vitro to the prealbumin fraction of serum. The decreases in retinol and thyroxine concentrations associated with fasting are therefore ascribed to a decrease in the concentration of transthyretin in circulation.

ISSN:0098-4108    

DOI:10.1080/15287399409531871

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

In the present study we determined the effect of repeated administration of manganese chloride on the binding parameters of [3H]quinuctidinyl benzilate (3H‐QNB) in striatum, frontal cortex, and hippocampus of mice. Daily intraperitoneal injections of manganese chloride (5 mg Mn/kg) 5 d/wk during 9 wk did not alter the receptor density (Bmax) and the dissociation constant (Kd) of3H‐QNB in the different brain regions studied. These results suggest that chronic treatment with manganese does not affect the binding characteristics of3H‐QNB to the cholinergic muscarinic receptors in mouse brain.

ISSN:0098-4108    

DOI:10.1080/15287399409531872

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

A recent report has indicated that cadmium‐induced testicular damage in CF‐1 mice can be prevented by pretreatment with calmodulin inhibitors such as chhrpromazine (CPZ), trifluoperazine, or N‐(6‐aminohexyl)‐5‐chloro‐1‐naphthalene sulfonamide (W‐7). However, the basis of this tolerance to cadmium is unclear and has not been demonstrated in any species other than mice. Thus, we examined the effects of the calmodulin inhibitor CPZ on cadmium toxicity in male Wistar (WF/NCr) rats. A single sc injection of 25 μmol CdCI2/kg proved nonlethal over 24 h but caused the typical spectrum of testicular lesions and increases in hemoglobin content (as assessed by hemoglobin absorbance in testicular supernatant). Pretreatment with 40 μmo/ CPZ/kg had no effect on cadmium‐induced testicular lesions but did reduce testicular hemoglobin content, while 120 μmot CPZ/kg moderately reduced the severity of testicular lesions and hemoglobin contenls. CPZ pretreatment in some cases increased cadmium content in liver and reduced testicular content but had no effect on renal levels. Cadmium treatment markedly increased hepatic and renal metal‐lothionein (Ml), a metal‐binding protein often associated with tolerance to cadmium. CPZ alone likewise increased hepatic Ml and Ml mRNA, but did not modify renal Ml, renal Ml mRNA, or testicular Ml mRNA. In contrast to liver and kidney, testicular cadmium‐binding protein (TCBP) decreased in rats exposed only to cadmium or to CPZ, while CPZ pretreatment had no further effect on cadmium‐induced reductions in TCBP levels. These results indicate that, like mice, CPZ in rats can reduce the testicular toxicity of cadmium as indicated by CPZ‐'mduced reductions in testicular vascular lesions and hemoglobin contents. However, in rats CPZ has a less dramatic effect on such cadmium‐induced lesions than in mice. The CPZ‐induced stimulation of hepatic Ml gene expression or modification of toxicokinetics may both play roles in this acquired tolerance to cadmium.

ISSN:0098-4108    

DOI:10.1080/15287399409531873

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

We investigated the metabolism of 3‐nitrofluoranthene by filamentous fungus, Cunning‐hamella elegans ATCC 36112. Cunninghamella elegans metabolized about 72% of the 3‐nitro[3,4‐14C]fluoranthene added during 144 h of incubation to 2 major metabolites. These metabolites were separated by reversed‐phase high‐performance liquid chromatography and identified as 3‐nitrofluoranthene‐8‐sulfate and 3‐nitrofluoranthene‐9‐sulfate by ‘H nuclear magnetic resonance, UV‐visible, and mass spectral techniques. These results, in conjunction with previous studies on the fungal metabolism of fluoranthene, indicate that the nitro substituent at the C‐3 position of fluoranthene sterically hinders epoxidation and shifts metabolism to the C‐8 and C‐9 positions. Since the phenolic microsomal metabolites of 3‐nitrofluoranthene are mutagenic, the formation of sulfate conjugates of 8‐ and 9‐hydroxy‐3‐nitrofluoranthene by C. elegans suggests that the fungal metabolic pathways may be beneficial for detoxification of this ubiquitous pollutant.

ISSN:0098-4108    

DOI:10.1080/15287399409531874

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

摘要:

This report updates the risk assessment by Crump and Allen (1984) for benzene‐induced leukemia that was used by OSHA (1987) to support its reduction of the permissible exposure limit (PEL) to 1 ppm and that also was the basis for EPA's (1985) interim “unit risk” for benzene. The present study derives new risk estimates using data from follow‐up through 1987 (whereas the earlier assessment only had follow‐up available through 1978), and using new exposure estimates for this cohort developed by Paustenbach et al. (1992) that account for a number of factors that were unknown or not fully evaluated in earlier exposure assessments. There was a significant excess of acute myelocytic or acute monocytic leukemia (AMML, the only forms of acute nonlymphatic leukemia observed) in this cohort, and this end point also exhibited a strong dose‐response trend. AMML was the only hematopoietic or lymphatic cancer that was clearly linked to benzene exposure. However, quantitative estimates of risk based on modeling either AMML or all leukemia differed by only 20%. Differences between the two Pliofilm plant locations in the occurrence of AMML were not statistically significant (.12 ≤ p ≤ .21) after differences in levels of benzene exposure were taken into account. The Paustenbach et al. exposures predicted a quadratic dose response, based on a measure of exposure that weighted intensity of exposure more heavily than duration of exposure. The best‐fitting quadratic models predicted an additional lifetime risk of a benzene‐related death from 45 yr of exposure to 1 ppm of between 0.020 and 0.036 per thousand. Statistical confidence intervals (90%) on these estimates were barely wide enough to include risk estimates based on linear dose response models. These linear models predicted risks of between 1.6 and 3.1 per thousand.

ISSN:0098-4108    

DOI:10.1080/15287399409531875

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor

ISSN:0098-4108    

DOI:10.1080/15287399409531867

出版商:Taylor & Francis Group    

年代:1994

数据来源: Taylor