摘要:

AbstractAllergic asthma can result when reactive low‐molecular‐weight chemicals (LMWCs) haptenate carrier proteins to form immunogenic conjugates, which then induce specific allergic antibodies. As part of an overall assessment process for evaluating the allergenic potential of LMWCs, anin vitrotest for detecting the covalent derivatization of proteins by LMWCs was developed. In the assay, globulin‐free serum albumins were incubated with increasing concentrations of a given LMWC and the mixtures separated via reversed‐phase high‐performance liquid chromatography (HPLC). Derivatization was monitored by shifts in the retention time of native versus modified protein. Retention time shifts were seen for most haptens when incubated with human serum albumin at a 50:1 (hapten:protein) starting molar ratio. Some haptens changed the retention time of the protein at a 5:1 initial ratio. Almost all chemicals that non‐covalently bind to proteins did not change the protein retention time, even when incubated at 1500:1 molar ratios. The screen correctly identified 12/14 known human allergenic haptens and 23/24 non‐allergenic LMWCs. It cannot detect sensitizers which must be metabolized into reactive haptens. This screen can be incorporated into an overall risk assessment approach for evaluating chemicals as respirat

ISSN:0260-437X    

DOI:10.1002/jat.2550130503

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe SOS Chromotest was carried out on leachates of ten industrial wastes with the standard procedure and a miniaturized version with microplates. The two methods gave identical results in nine samples (eight negative and one positive). A simple additional manipulation is described for the identification of the false positive response that is frequently observed with complex mixtures. It involves challenging the SOS Chromotest bacteria with samples (having previously shown a positive genotoxic response) just before the enzymatic activities (i.e. β‐galactosidase and alkaline phosphatase) are estimated colorimetrically. This additional step eliminates discrepancies between the results for the standard and the miniaturized procedur

ISSN:0260-437X    

DOI:10.1002/jat.2550130504

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe effect of nine monoalkyl esters of meso‐2,3‐dimercaptosuccinic acid (DMSA) on203Hg retention after a single i.p. dose was evaluated in 6–7 week‐old female albino rats. The monoesters were the monomethyl (MMDMS), monoethyl (MEDMS), mono‐n‐propyl (Mn‐PDMS), monoisopropyl (Mi‐PDMS), mono‐n‐butyl (Mn‐BDMS), monoisobutyl (Mi‐BDMS), mono‐n‐amyl (Mn‐ADMS), monoisoamyl (Mi‐ADMS) and mono‐n‐hexyl (Mn‐HDMS). Dimercaptosuccinic acid or one of the monoesters were administered at a dose of 0.25 mmol kg−1body wt. twice, i.e. 30 min and 24 h after203Hg administration. The whole body (WB) radioactivity was determined on the 2nd, 4th and 6th days. The radioactivity in the carcass (C) whole body without the gastrointestinal tract), liver (L), both kidneys (K) and brain (B) was determined 6 days after203Hg administration. All treated animals had a significantly lower body burden of mercury than the controls. The reduction of203Hg retention in WB and other body compartments was higher in animals treated with monoesters than in rats treated with DMSA. The relative effectiveness of the monoesters was dependent on the nature of the alkyl groups, the efficiency being higher in higher analogues. Maximum activity was attained with the C5(Mn‐ADMS, Mi‐ADMS) and C6(Mn‐HDMS) esters. These chelators reduced WB, C, L, K and B mercury retention by 90, 89, 76, 93 and 80%, respectively. Iso derivatives were more efficient than the normal isomers (Mi‐PDMS>Mn‐PDMS; Mi‐BDMS>Mn‐BDMS; Mi‐ADMS>Mn‐ADMS). The effect of all monoesters w

ISSN:0260-437X    

DOI:10.1002/jat.2550130505

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe leakage of mitochondrial (m‐) and cytosolic (s‐) aspartate aminotransferases (glutamic‐oxaloacetic transaminase: GOT) from isolated hepatocytes exposed to halothane was investigated immunohistochemically. In control isolated hepatocytes, a large number of cells were immunopositive (m‐GOT, 85%;s‐GOT, 98.5%) at various intensities. Reaction products of m‐GOT‐immunohistochemistry (m‐GOT‐I) were seen exclusively in mitochondria, while those ofs‐GOT (s‐GOT‐I) were seen in the cytoplasm. When treated with low concentrations of halothane (up to 0.75%), the number of strongly m‐GOT‐I‐immunopositive cells was reduced to half, while that ofs‐GOT‐I showed no noticeable change. The number of m‐GOT‐I‐immunonegative cells showed a negligible increase, while that ofs‐GOT‐I increased gradually. At higher concentrations of halothane (1% or more), strongly immunopositive cells in both m‐ ands‐GOT‐I almost disappeared, while immunonegative cell numbers predominantly increased. This study showed that the isolated hepatocyte system was not homogeneous with regard to the quantity of GOT isozymes, and that halothane could induce the leakage of these isozymes from hepatocytes, along with inducing ultrastructural abnormalities, even at the lowest concentration used (0.5%). Furthermore, the data appear to indicate that the sensitivity of isolated hepatocytes to halothane is dependent on the nature of the hepatocyte itsel

ISSN:0260-437X    

DOI:10.1002/jat.2550130506

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractIncidence of numerous human poisonings by quinalphos (Ekalux®, Bayrusil®) in agricultural areas near Belgrade initiated this study on the ability of the compound to inhibit hen brain neuropathy target esterase, acetylcholinesterase and plasma butyrylcholinesterasein vivo. Hens were treated with a single oral dose ranging from 25 to 600 mg kg−1quinalphos (LD50= 72 mg kg−1) or 500 mg kg−1triorthocresyl phosphate (positive control), sacrificed 24–96 h later for enzyme assays and monitored for 25 days for evaluation of walking impairments. High inhibition (>80%) of both cholinesterases was obtained with 25 and 50 mg kg−1quinalphos. Doses of 200 and 600 mg kg−1of the agent inhibited up to 23 and 28% of hen brain neuropathy target esterase activity, respectively. Clinical signs of neuropathy were not seen. Quinalphos was slowly absorbed from the gastrointestinal tract, as indicated by the severity of the cholinergic symptoms and the inhibiton of neuropathy target esterase, which reached its maximum 72 and 96 h after poisoning. The results suggest that quinalphos, at doses tested, has no ability to cause delayed neuropathy in hens without showing signs of severe cholinergic

ISSN:0260-437X    

DOI:10.1002/jat.2550130507

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe induction of chromosomal aberrations and sister chromatid exchangein vivoin mouse spleen and bone marrow as well asin vitroin cultured mouse spleen cells by the insecticide ‘Cypermethrin’ (cistrans1:1) was investigated.The percentage of chromsomal aberrations in the spleen and in the bone marrow as almost the same and reached its maximum 6 h following i.p. injection. The aberrations induced were chromatid and chromosome gaps, fragments and tetraploidy. The insecticide caused a significant and dose‐dependent increase in the frequency of sister chromatid exchanges (SCEs) in mouse bone‐marrow cells: it reached 11.12 ± 0.05 per cell after treatment with Cypermethrin at 300 mg kg−1body wt. compared with 3.7 ± 0.14 per cell and 4.4 ± 0.26 per cell in the solvent and control, respectively.The percentage of viable cells in mouse spleen cell cultures reached 87.4% and 99.9% relative to the control after treatment of the cell cultures with 10−3and 10−7Cypermethrin, respectively. All the tested concentrations of Cypermethrin (0.25–400 μg ml−1) induced a high percentage of metaphases with chromosomal aberrations after 4 h of treatment. The mean frequency of SCEs per cell reached 15.1 ± 0.05 after treatment with Cypermethrin at 4.00 μg ml−1compared with 8.6 ± 0.23 and 5.9 ± 0.39 in the solvent and control, respectively.The results indicate that Cypermethrin is genotoxic in mouse spleen and bone marrow as well as in

ISSN:0260-437X    

DOI:10.1002/jat.2550130508

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractSeed extracts obtained fromLupinus albusandLupinus angustifoliusby treatment with 48% ethanol contained ca. 10% alkaloids (on a dry weight basis) and were non‐toxic. Their acute toxicity (LD50) in the mouse is>4000 mgkg−1body wt.After fractionation, the extract fromL. angustifoliusseeds afforded several fractions with differing toxicities (LD50750–4000 mg kg−1body wt.).None of the fractions testedin vitrowere toxic. The results obtained showed that, in spite of the alkaloids, other low‐molecular‐weight constituents present significantly modified the toxicity of the lup

ISSN:0260-437X    

DOI:10.1002/jat.2550130509

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractUsing the human hepatoma cell line, HepG2, and the BALB/c mouse fibroblast cell line, 3T3, as the bioindicators in the neutral red cytotoxicity assay, the effect of hydroxyl substitution on the toxicity of 1,4‐naphthoquinone was studied. The sequence of potency for the quinones was 5,8‐dihydroxy‐1,4‐naphthoquinone>5‐hydroxy‐1,4‐naphthoquinone>1,4‐naphthoquinone>2‐hydroxy‐1,4‐naphthoquinone. Pretreatment of the cells with dicoumarol, an inhibitor of DT‐diaphorase, enhanced the cytotoxicity of 1,4‐naphthoquinone but not of the hydroxylated naphthoquinones. Pretreatment of the BALB/c cells with buthionine sulfoximine, an inhibitor of glutathione synthesis, enhanced the sensitivity of the cells to all the hydroxylated naphthoquinones but not to 1,4‐naphthoquinone. A similar pretreatment of the HepG2 cells with buthionine sulfoximine enhanced the toxicity of the 2‐hydroxy‐ and 5,8‐dihydroxy‐1,4‐naphthoquinones but not of 5‐hydroxy‐1,4‐naphthoquinone or of 1,4‐naphthoquinone.Some differences were noted in the responses to the hydroxylated 1,4‐naphthoquinones between buthionine sulfoximine‐treated replicating cells and buthionine sulfoximine‐treated isolated rat hepatocytes, a non‐replicating cell in culture. The use of a replicating cell system in studying the mechanisms of the cytotoxicity of quinones may be an important adjunct to studies using the isolate

ISSN:0260-437X    

DOI:10.1002/jat.2550130510

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractSulfur mustard (HD) (bis(2‐chloroethyl)sulfide) is a strong alkylating agent with known mutagenic and suspected carcinogenic properties, but occupational health standards have not been established. The purpose of this study was to determine the dominant lethal effect in male and female rats dosed orally with HD, for which currently available data are ambiguous.Sprague‐Dawley rats of each sex, 6–7 weeks old, were orally administered 0, 0.08, 0.20 or 0.50 mg kg−1HD 5 days a week for 10 weeks, after which dominant lethal studies were conducted during the post‐exposure period. The studies were conducted in two phases: a female dominant lethal phase in which treated or untreated males were mated with treated females and their fetuses were evaluated 14 days after copulation; and a male dominant lethal phase in which treated males cohabited with untreated females for 5 days and fetuses were evaluated 14 days after the mid‐point of the week of cohabitation, for each of 10 weeks. In addition, motility, population size and morphology were measured in sperm obtained from the cauda epididymis.Parental growth rates were reduced in both sexes treated with the high level of HD. Female dominant lethal effects were not observed, although significant male dominant lethal effects were observed in HD‐exposed male rats mated to untreated females at 2 and 3 weeks' post‐exposure. These effects, which included increases of early fetal resorptions and preimplantation losses and decrease in total live embryo implants, were most consistently observed at a dose of 0.50 mg kg−1. A significant P(P<0.05) increase in the percentage of abnormal sperm was detected in males exposed to 0.50 mg kg−1HD. The timing of dominant lethal effects is consistent with an effect during the post‐meiotic stages of spermatogenesis, possibly involving the generally

ISSN:0260-437X    

DOI:10.1002/jat.2550130511

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe acute pulmonary function response to graded levels of a low toxicity dust was studied in guinea pigs. Four groups of five male guinea pigs each were exposed to mean concentrations of 0, 0.25, 1.01 and 5.39 mg Foundry Hill Clay I−1air with mass median aerodynamic diameters of 2.6, 4.6 and 6.7 μm, respectively. There was a 15‐min pre‐exposure period to clean air, a 1‐h exposure to the test atmosphere and then a 1‐h recovery period with exposure to clean air. Concentration‐related changes, compared to the pre‐exposure period, occurred with a rapid onset in a number of parameters. Generally, the severity of observed effects increased with exposure time and, therefore, with inhaled dose. Statistically significant changes (P<0.05) were observed in tidal volume, dynamic compliance, dynamic resistance, flow, pressure and minute volume during the last 15 min of exposure. The observed changes were consistent with acute bronchoconstriction. These effects reversed rapidly and there were no significant changes 1 h post‐exposure. These results suggest that adverse physiological responses of short duration can occur when animals are exposed via inhalation to low‐toxicity materials in the concentration r

ISSN:0260-437X    

DOI:10.1002/jat.2550130512

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY