摘要:

AbstractNitroguanidine (NG) and its degradation product nitrosoguanidine (NSG) were evaluated for their mutagenic potential by usingDrosophila melanogastersex‐linked recessive lethal (SLRL) assay. Following 72 h of feeding exposure, NG and NSG at concentrations of 4–8 μg ml−1and 15–20 mg ml−1, respectively, were not mutagenic in the test system. The frequencies of mutations for NG and the negative control were 0.188% and 0.096%, respectively. The frequencies of mutations for NSG and the negative control experiments were 0.049% and 0.05%, respectively. The positive control mutation frequencies were 15% and 17.8% for the two assays. The differences between the mutation frequencies of NG and NSG and their negative controls were not s

ISSN:0260-437X    

DOI:10.1002/jat.2550130404

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractOTTO Fuel II (OFII) is a propellent used by the United States Navy in its Mk 46 and Mk 48 torpedoes. Owing to the possibility of human exposure during fueling and defueling operations, studies were initiated to determine if OFII was a developmental toxin. Phase I of the investigation involved dosing four groups of time‐mated Fischer‐344 rats with OFII. The fuel was administered dermally at the rate of 0, 400, 2000 and 4000 mg kg−1day−1. A significant reduction in body weight was seen at necropsy in dams receiving 2000 and 4000 mg kg−1day−1of OFII. Fetuses from these dams also weighed significantly less than control fetuses.Phase II of the investigation involved dosing of artificially inseminated rabbits with OFII. The fuel was administered to the skin of the animal's back at the rate of 0, 100, 316 and 1000 mg kg−1day−1. Maternal toxicity was evidenced by a significant reduction in body weight of the dams in the 1000 mg kg−1day−1dose group on days 20 and 25 of gestation. There were no significant differences observed in maternal weight or fetal weight at necropsy. Morphological examination of both rat and rabbit fetuses failed to reveal significant evidence of

ISSN:0260-437X    

DOI:10.1002/jat.2550130405

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractA single oral dose of di‐n‐butyl phthalate (DBP) to male rats caused a sloughing of the germ cells at 6 h both with a decrease in the activity of succinate dehydrogenase (SDH) in the Sertoli cells and in the Sertoli‐germ connection and with an increase in the activity of lactate dehydrogenase (LDH) in the germ cells. Increases in transferrin (Tf) concentrations were observed in the Sertoli cells, Sertoli‐germ connection, epididymis‐ductus deferens and liver of rats. Decreases in Tf and ferritin (Ft) levels were observed in the seminal vesicle and seminiferous lumen, respectively. An increase in favin adenine dinucleotide (FAD) level was found in the interstit

ISSN:0260-437X    

DOI:10.1002/jat.2550130406

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractA white spirit/naphtha, three kerosines, two gas oils and a catalytically cracked light cycle oil (LCO) were applied topically to mice, three times a week for up to 6 weeks, and skin changes were examined histopathologically at intervals.The changes within 1 week of treatment appeared to depend on the effect that the physicochemical properties of each type of product had on their penetration through the skin surface or via hair follicles. With white spirit the most prominent change was widespread epidermal necrosis occurring after the second treatment, implying that the lowest boiling point materials penetrate mainly through the surface epidermis. The earliest effects with kerosines were within and around hair follicles with epidermal degeneration developing later, suggesting a predominance of follicular entry. Gas oils and LCO produced similar changes to kerosines within 1 week, gas oils producing a slower and less severe response and LCO a more severe response. In skin examined after 1–6 weeks of treatment with all middle distillates, repeated cycles of necrosis and healing responses were evident; this implied that once the epidermal barrier layer had been damaged, follicular entry became less important.The severity of the skin changes observed with these middle distillates was probably sufficient for skin tumours to arise by a non‐genotoxic mechanism if a similar treatment regime was used in a long‐term skin painting study. A method of avoiding excessive skin irritation is therefore essential in such a study in order to obtain a reliable prediction of the human hazard of such mate

ISSN:0260-437X    

DOI:10.1002/jat.2550130407

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractTri‐o‐cresyl phosphate (TOCP) is used commercially as a plasticizer and flame retardant. The disposition, metabolism, elimination and transplacental uptake of [phenyl‐U‐14C]TOCP and/or its metabolites, in pregnant and non‐pregnant mice, were examined. Pregnant (18th‐day gestation) and non‐pregnant, ICR mice were given an i.v. dose of [14C]TOCP (557 μCi kg−1; Specified activity 4.83 μCi μmol−1). At various time intervals (1, 24, 48 and 72 h) the animals were processed for whole‐body autoradiography (WBA). Over 72 h the nonpregnant mice excreted 55% of the14C in the urine and 9% in the feces, while excretion in the urine and feces by the pregnant mice was 50% and 9% of the total dose, respectively. The WBA and its computerassisted image analysis indicated extensive distribution of the14C label originally dosed as [14C]TOCP in pregnant mice and their fetuses. The retention of radioactivity in organs such as lung, spleen, gall‐bladder and liver of mother and its fetuses suggest that these are the target sites of TOCP toxicity. The distribution in non‐pregnant and pregnant mice and in the fetal tissues followed a similar pattern in uptake and retention until 72 h. Brain and spinal cord had the least amount of [14C]TOCP. This finding may support reports that explain the insensitivity of the mice towards organophosphate‐induced delayed n

ISSN:0260-437X    

DOI:10.1002/jat.2550130408

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractRat lung fibroblasts were cultured for 24 and 48 h with UICC standard reference asbestos samples of amosite, crocidolite or Canadian chrysotile at various concentrations, and thiobarbituric acid‐reactive substances (TBARS) in the media and the cells were measured. Tests by the trypan blue dye‐exclusion method showed that cell viability was 80 ± 5% (mean ± SD) and 71 ± 6% when cultured for 48 h in the presence of 500 μg ml−1of amosite and crocidolite, respectively, but was not affected by chrysotile. In cultures for 24 and 48 h, both chrysotile and crocidolite at>250 μg ml−1significantly increased TBARS in the medium, whereas amosite did so at>500 μg ml−1.TBARS in the cells was not increased significantly by chrysotile at any concentration in the cultures for 24 and 48 h, but crocidolite at>250 μg ml−1significantly increased TBARS in the cells when cultured for 24 or 48 h. Although amosite at all concentrations tested did not increase significantly TBARS in the cells of the 24‐h culture, it did increase TBARS significantly in the cells when cultured for 48 h at a concentration of 500 μg ml−1amosite.The increases of TBARS in media of the cultures with asbestos were accompanied by increases of lactate dehydrogenase (LDH) activity in the media, indicating the leakage of the enzyme from the cell into the media. The activity of LDH and the amount of TBARS showed a good correlation with each other, with a significant correlation coefficient value of 0.655.Thus, the amount of TBARS produced during the culture seemed to change, depending on both the asbestos concentration and the inherent properties. The findings suggest that when certain types of asbestos are cultured with rat lung fibroblasts the cell membranes are peroxidized to cause disintegration of the membrane structure, followed by leakage of cellu

ISSN:0260-437X    

DOI:10.1002/jat.2550130409

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe experiments reported herein were designed to identify the best assay of diacetylmonoxime (DAM) in biological fluids, with particular emphasis on detection limits. Initially, four variations of the assay of urea with excess DAM were compared. The best method, published in 1977, was one that includes thiosemicarbazide, 4‐aminoantipyrine and ceric ammonium sulphate in the acid reagent; it is fast, gives a reasonably stable chromophore and displays good linearity. However, the reaction was two or more times less sensitive when applied to the assay of DAM, with urea in excess, by interchanging the amounts of urea and DAM. Further, the calibration graphs did not pass through the origin, and one of the methods gave a mixture of two chromophores. None approached the sensitivity of a DAM‐urea reaction specifically designed to assay biacetyl (formed from DAM by acid hydrolysis) and published in 1968. This method, using antipyrine and arsenicosulphuric acid, is also fast, with good linearity and a stable chromophore, but is sensitive to interference by plasma and urine. An alternative photometric assay that does not involve urea was equally sensitive. It had the advantage of less interference by plasma and urine but was more time‐consuming. Both of these photometric methods had a limit of detection of ca. 0.2 μg DAM, similar to that of a high‐performance liquid chromatography (HPLC) assay. Sample clean‐up is necessary before application of the

ISSN:0260-437X    

DOI:10.1002/jat.2550130410

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe mutagenic potential of zinc pyrithione (Znpt) was evaluatedin vitroin theSalmonella/mammalian microsome plate incorporation mutagenicity (Ames) assay and the CHO/HGPRT gene mutation assay. The clastogenic potential of Znpt was evaluatedin vivousing the mouse micronucleus test. Znpt was negative in the Ames test in five tester strains in the presence and absence of rat liver microsomal enzymes when assayed at concentrations ranging between 10 and 333 μg per plate and between 0.03 and 33 μg per plate, respectively. Znpt also produced negative results in the CHO/HGPRT assay. No significant increases in mutant frequencies were seen in the presence and absence of rat liver microsomal enzymes. In each case, the highest concentrations reduced cellular viability by 83% and 85%, respectively. Znpt also did not induce increased frequencies of micronuclei in mouse bone marrow cells when tested at the maximally tolerated dose (MTD) (44 mg kg−1). These data support the conclusion that Znpt lacks genotoxic activity under the conditions of these te

ISSN:0260-437X    

DOI:10.1002/jat.2550130411

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

Abstract2,2,4‐Trimethylpentane (TMP), a nephrotoxic component of unleaded gasoline in male but not female rats, undergoes oxidative metabolism to yield 2,2,4‐ and 2,4,4‐trimethylpentanol, pentanoic acid and 5‐hydroxypentanoic acid. We have examined the effect of three of these pentanoic acid metabolites on the renal transport of the organic anionp‐aminohippurate (PAH) and the organic cation tetraethylammonium (TEA) in renal cortical slices from male Fischer 344 rats. 2,4,4‐Trimethylpentanoic acid, the major urinary metabolite in rats, produced a selective decrease in the accumulation of PAH without affecting TEA accumulation. Kinetic analysis showed that 2,4,4‐trimethylpenanoic acid was a competitive inhibitor of the organic anion transport system, with aKiof 4 mM. 2,4,4‐Trimethyl‐5‐hydroxypentanoic acid also showed selective inhibition of PAH transport, while 2,2,4‐trimethylpentanoic acid was less selective and reduced both PAH and TEA transport. Additional studies with radiolabeled 2,4,4‐trimethylpentanoic acid showed that there was a time‐and concentration‐dependent accumulation of radioactivity into slices of renal cortex. However, experiments conducted at 4°C and studies with metabolic inhibitors, or with an inhibitor of organic anion transport, indicated that little of the accumulated material was entering the cell. We conclude from these studies that the pentanoic acid metabolites formed from 2,2,4‐trimethylpentane are not actively transported by the renal organic anion transport system. In summary,in vitrothe pentanoic acid metabolites appear to bind to renal cortical tissue and there

ISSN:0260-437X    

DOI:10.1002/jat.2550130412

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe effects of benzene hexachloride (BHC), an organochlorine pesticide, on cell growth and phosphatase activities were studied in the growing and developing stages of cells of the cellular slime mouldDictyostelium discoideumexposed to BHC (containing α‐, β‐, δ‐ and γ‐isomers) at concentrations of ≥ 60 μg ml−1. A significant increase in acid and alkaline phosphatase activities was recorded in both growing and differentiatingDictyosteliumcells treated with different doses (≥ 60 μg/ml) of BHC. The cytotoxicity of BHC has been correlated with the stimulation of acid and alkaline phosphatase activiti

ISSN:0260-437X    

DOI:10.1002/jat.2550130413

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY