摘要:

AbstractBenzocaine (BNZ) and lidocaine (LC) are commonly used topical (spray) anesthetics approved for use in humans. Benzocaine has structural similarities to methemoglobin (MHb)‐forming drugs that are current candidates for cyanide prophylaxis, while LC has been reported to increase MHb in man. In this study, we compared MHb and sulfhemoglobin (SHb) production in three groups of Macaques (Chinese rhesus and Indian rhesus (Macaca mulatta) and pig‐tailed macaques (Macaca nemestrina)) after exposure to BNZ and LC. Formation of SHb, unlike MHb, is not thought to be reversible and therefore is considered to be of greater toxic significance. Both MHb and SHb levels were measured periodically on a CO‐Oximeter. All rhesus macaques (n= 8) were administered an intratracheal/intranasal) dose of 56 mg (low dose) or 280 mg (high dose) of BNZ or 40 mg of LC in a randomized cross‐over design (all animals received all three treatments). Pig‐tailed macaques (n= 6) were given an intranasal dose of 56 mg of BNZ and 40 mg of LC. As no differences in the peak MHb or time to peak (mean ± SD) were observed among the three macaque subspecies, the data were pooled. Lidocaine did not cause MHb or SHb formation above baseline in any monkey. In contrast, all monkeys (n= 14) had a significant elevation in peak MHb formation after 56 mg of BNZ, which ranged from 4.0% to 19.4% with an average of 8.6 ± 4.0% (mean ± SD), with peak MHb levels reached at 30 min. The monkeys given the high dose of BNZ (n= 8) demonstrated higher peak MHb levels (P<0.05) than the lower dose of BNZ: 14.7 ± 6.5% (mean ± SD) as the time to peak increased to 45 min. Slight increases in SHb levels (0.02–0.04 mm 1−1rise) measured (P<0.05) after low and high BNZ doses were 54% and 75% higher than baseline SHb levels after LC. This study indicates that benzocaine applied topically in non‐human primates can readily increase MHb concentrations within 30 min to clinically relevant levels required for cyanide prophylaxis, but LC does not. The variability in the peak Hb levels after BNZ is likely to be due to the variability in absorption and/or metabolism of the drug. In addition, the slight increase in SHb seen in BNZ groups should prompt investigators to also evaluate this toxic Hb component when evaluati

ISSN:0260-437X    

DOI:10.1002/jat.2550150304

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractFour process streams derived from the EDSEDS is a designaiton for a direct coal liquefation process and was descriptive of an early stage in process development.direct coal liquefaction process were evaluated in twoin vitroassays to screen for carcinogenic potential: theSalmonella/mammalian microsome mutagenicity assay and the Syrian hamster embryo morphologic transformation assay. Three high boiling liquids (two recycle solvents, nominal boiling range 200–425°C; and a fuel oil blend, nominal boiling range 200–538°C) were active in both assays. A hydrotreated naphtha sample (<200°C) was not active in either. TheSalmonelladata agreed qualitatively with results of dermal carcinogenesis studies; however, quantitative differences as measured by the estimation of mutagenic potency were apparent. The lack of quantitative agreement may have been related to the fact that the dermal carcinogenic activity of coal‐derived synthetic fuels is predominantly associated with neutral polycyclic aromatic hydrocarbons, whereas activity in theSalmonellaassay is strongly influenced by the presence of aromatic amines and nitroaromatic compounds.Two modifications of theSalmonellaassay—detergent disperson and hamster S9 activation—were examined. These techniques improved assay performance for some but not all of the coal liquids. The differences in response may have been related to compositional differences in the var

ISSN:0260-437X    

DOI:10.1002/jat.2550150305

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThis study represents the first systematic attempt to rank methemoglobin‐forming agents. It is a quantitative potency ranking study utilizing linear regression analysis of dose‐response data for comparative purposes. Six agents that are direct‐acting and eight that require bioactivation were tested for their ability to induce methemoglobin formation in Dorset sheep erythrocytes under definedin vitroconditions. The agents were then ranked according to three complementary methods based on the slope of the linear regression, the calculated dose expected to induce a given amount of methemoglobin formation and the calculated percentage methemoglobin response induced by 1 mmol 1−1of the agent. The direct‐acting agents, ranked from most to least potent inducers of methemoglobin formation, are:p‐dinitrobenzene>o‐dinitrobenzene>copper = nitrite>chlorite>chlorate. The ranking from most to least potent inducers of the bioactivated agents are: α‐naphthol>p‐nitroaniline>m‐nitroaniline,o‐nitroaniline>p‐nitrotoluene = aniline>m‐nitrotoluene =o‐nitrotoluene. The ranking procedures are discussed and issues of interindividual variation and agent‐specif

ISSN:0260-437X    

DOI:10.1002/jat.2550150306

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractIn the main study, tritium‐labelled benzo[a]pyrene ([3H]BaP) was added to oils of a wide range of viscosity (from 13.5 to ca. 8000 cSt at 40°C) and these were applied once to mouse skin under conditions where grooming was either allowed or prevented. The binding of [3H]BaP to epidermal protein and DNA was assessed. In addition, some studies were conducted to investigate the effect of prior oil exposure on binding levels and to compare binding levels following single and multiple application.It was found in the main study that the binding of [3H]BaP to both DNA and protein was increased as the viscosity of the oil vehicle decreased. Whereas only a twofold difference in DNA binding was found between the lowest and highest viscosity oil vehicle if grooming was allowed, a 14‐fold difference was seen if grooming was prevented. This was due to much higher binding levels with low viscosity oils when grooming was prevented. Protein binding showed similar results, although the difference between the grooming and non‐grooming situations was slightly less. Whether grooming was prevented or not, both DNA and protein binding of [3H]BaP were found to be inversely proportional to the logarithm of viscosity of the oil vehicle, but when grooming was prevented, the slope for DNA binding was 10 times steeper than when it was permitted.Exposure of the skin to either high or low viscosity oils prior to the application of [3H]BaP in the same oil inhibited the binding to DNA but not to protein. In experiments where multiple applications of [3]BaP in oil were given, the difference in DNA binding between low and high viscosity oils was similar to that after a single application. This implied that the relative bioavailability of polycyclic aromatic hydrocarbons from oils of differing viscosity, as assessed following single application, is reasonably predictive of that following multiple applications.In considering the relevance of the findings of the main study to long‐term animal studies and to human hazard, it is suggested that the situation where grooming was permitted is likely to be most relevant to animal studies, whereas that where grooming is prevented is more likely to represent human exposure. Hence, borderline positive findings in long‐term mouse skin painting studies with low‐viscosity oils should be regarded more seriously than similar findings with viscous oils. The findings should also be of assistance in making predictions of carcinogenicity from ana

ISSN:0260-437X    

DOI:10.1002/jat.2550150307

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractFrog Embryo Teratogenesis Assay—Xenopus(FETAX) testing of a series of diverse hazardous waste‐site soil samples was performed to evaluate the efficacy of FETAX as a rapid developmental toxicity screening tool for environmental hazard assessment. Soil samples were collected from six different hazardous waste sites, three from eastern and three from western Washington State. The type of waste site samples studied, based on the contaminants identified, included: heavy metals (2), polymnuclear aromatic hydrocarbons, petroleum products (2) and organochlorine pesticides. Three to five samples from each site representing baseline and increasing levels of contamination were collected. Aqueous extracts of the soil samples were prepared and used for FETAX studies. Samples collected from the polynuclear aromatic hydrocarbon‐ and petroleum product‐contaminated sites induced greater levels of embryolethal effects, although embryonic malformation was also observed. The metal‐contaminated sites induced greater levels of embryonic malformation, but induced less embryolethality than the other samples evaluated. The organochlorine pesticide‐contaminated site samples caused significant levels of embryonic deformities but failed to induce embryolethal effects. Results from these studies suggested that FETAX was sensitive enough to detect low levels of developmental toxicants but robust enough to be suitable for aqueous soil extract testing. FETAX may be used as a component of a battery of tests designed to assess potential ecolog

ISSN:0260-437X    

DOI:10.1002/jat.2550150308

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractUrinary 1‐OH‐pyrene, a metabolite of pyrene, is a sensitive biological marker for dermal absorption of pyrene in man. In order to determine whether this metabolite is a reliable biomarker of cutaneous absorption of other polycyclic aromatic hydrocarbons (PAHs), the blood‐perfused pig ear model was used to compare the dermal absorption flux of pyrene with nine other PAHs after coal tar application. Cumulative absorption of PAHs into the perfusion blood, 200 min after application of an overdose of coal tar, ranged between 830 pmol cm−2for phenanthrene to less than 4 pmol cm−2for benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene, dibenzo[ah]anthracene and indeno[123‐cd]pyrene. The results of this study show that when pyrene is used as a marker compound for PAH absorption through pig skin, the cumulative absorption of PAHs with a lower molecular weight will be underestimated: fluorene, tenfold; phenanthrene, 12‐fold; anthracene and fluoranthene, ca. twofold. The percutaneous absorption of PAHs with a higher molecular weight than pyrene will be overestimated: e.g. benzo[a]pyrene, sevenfold; indeno [123‐cd]pyrene, ca. 100‐fold. It is likely that this conclusion is also valid for dermal PAH

ISSN:0260-437X    

DOI:10.1002/jat.2550150309

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractMonoisoamyl (Mi‐ADMS) and mono‐n‐hexyl (Mn‐HDMS) monoesters of meso‐2,3‐dimercaptosuccinic acid (DMSA) were given orally or parenterally for the mobilization of inorganic mercury in suckling and older rats. Chelators were administered at a dose of 2 × 0.5 mmol kg−1on two consecutive days 2 weeks after a single203Hg injection. Six days later, whole‐body, kidney, liver and brain radioactivities were determined in gamma scintillation counters.Both Mi‐ADMS and Mn‐HDMS were found to be superior to DMSA in mobilizing mercury from body and organs. The results were similar after oral or parenteral treatment. The efficiency of both monoesters was even higher in younger than in older rats. This is the first report on the mobilization of mercury from the body of sucklings under conditions of

ISSN:0260-437X    

DOI:10.1002/jat.2550150310

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe objective of this experimental work was to identify and compare the histopathological changes induced in the respiratory tract of Swiss mice exposed to repeated inhalation (4, 9 or 14 days) at typical concentrations of RD50, 0.3 × RD50and 3 × RD50of airborne chemicals. These substances were selected from ten chemical families: aldehydes, organic acids, alcohols, ketones, ethers, aromatic hydrocarbons, halogenated aromatic hydrocarbons, inorganic bases, amines and isocyanates.These experiments showed that the lesion intensity observed in the nasal passages varied with exposure duration and type of airborne chemical, but did not depend on the concentration of the substance. Results did not allow us to establish a relationship between the histopathological changes and the type of chemical family. No injuries were observed in trachea and lung

ISSN:0260-437X    

DOI:10.1002/jat.2550150311

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe influence ofs‐triazine compounds (atrazine, prometryne and deethylatrazine) on testosterone conversion and 5α‐dihydrotestosterone–receptor complex formation was studiedin vitroandin vivoin the rat prostate. A markedin vitroinfluence of atrazine and prometryne (from 0.465 to 1.392 μmol) and their mixtures (in total concentration, 0.928 μmol) on 5α‐dihydrotestosterone formation was detected. 5α‐Dihydrotestosterone‐specific receptor complex formation was inhibitedin vitroby ca. 0.5 μmol of atrazine or deethylatrazine and onlyin vivoby 6 mg of atrazine 100 g−1body wt. daily during 7 days in the prostate cytosol. The inhibition of the enzymic activities responsible for testosterone conversion and steroid hormone–receptor complex formation was non‐competitive and reversible, ands‐triazine compo

ISSN:0260-437X    

DOI:10.1002/jat.2550150312

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY

摘要:

AbstractThe fungicide substance QAS [N,N,N',N'‐tetramethyl‐N,‐N'‐di(8,15‐dichloropentadeca‐5,10‐dien)ethylenediamine methylsulphate] has a biphasic effect on the spontaneous electrical and mechanical activity of smooth‐muscle samples of rat corpus and guinea‐pig taenia coli.During the first phase of QAS application membrane depolarization and increased spontaneous spike frequency were recorded. The tone of the preparations (resting tone) increased transiently. Calcium ion‐entry blockers did not affect the contractile effect of QAS, but K+‐channel blockers and some modulators of the second messenger system abolished or decreased it.During the second phase depolarization increased progressively, spike frequency decreased and the increase in resting tone recorded during the first phase was eliminated.The results reveal that the long‐lasting depolarizing effect of QAS (in concentrations used for plant protection) probably inactivates the entry of Ca2+into the smooth‐muscle cells and

ISSN:0260-437X    

DOI:10.1002/jat.2550150313

出版商:John Wiley&Sons, Ltd.    

年代:1995

数据来源: WILEY