摘要:

AbstractIn 77 males exposed occupationally to vinyl chloride (VC), the plasma clearance (Cl) of99Tc–N(2,4‐dimethylacetanilido)iminodiacetate (‘HEPIDA’ complex) was determined. The results were juxtaposed with a scaled assessment of liver parenchyma performance based upon clinical examination and a series of biochemical tests. Detection of the diagnosable damage of liver parenchyma by means of the reduced clearance was sensitive (90%) at the reasonable specificity of 74%. Probability of exclusion of liver damage in patients with the clearance above 240 ml min−11.73 m−2amounted to 92%.There was a significant correlation between degree of exposure to VC and the frequency of low clearance values.It appears that the periodic determination of the99Tc–HEPIDA clearance in workers exposed to VC allows the assessment of incipient liver damage and signals the need for prophyla

ISSN:0260-437X    

DOI:10.1002/jat.2550090402

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractQuantification of nickel in animal soft tissue is of toxicological interest. A digestion method applying the use of microwave ovens for irradiating samples in Teflon digesters was developed. An acid mixture containing nitric acid (16 M, 1.0 ml g−1tissue), hydrochloric acid (6 M, 0.5 ml g−1tissue) and H2O2(30%, 1.0 ml g−1tissue) and irradiation at 600 W for 5 min were required for complete dissolution of tissue matrices and nickel compounds. Analyses of Ni in National Bureau of Standards Reference Material 1566 oyster tissue gave 0.87 ± 0.24 μg g−1(mean ± SD,n= 5), which was in agreement with the NBS certified value of 1.03 ± 0.19 μg g−1. Recoveries of 1–300 μg Ni added as nickel sulfate (highly soluble), nickel subsulfide (moderately soluble in biological fluids and acid) or nickel oxide (green high‐temperature oxide, low solubility in biological fluids and acid) to lung, liver, lymph node and kidney were quantitative, except in the case of nickel sulfate added to kidney, where recovery was less than quantitative for 1–10 μg Ni. The method appears effective for digestion of a variety of tissues

ISSN:0260-437X    

DOI:10.1002/jat.2550090403

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe role of aromaticity in the nephrotoxic potential ofN‐arylsuccinimides was studied in male Fischer 344 rats. Rats were administered a single intraperitoneal (i.p.) injection of anN‐arylsuccinimide derivative (0.4 or 1.0 mmol/kg) or sesame oil (2.5 ml/kg), and the renal function monitored at 24 and 48 h. The parent compound in this series,N‐phenylsuccinimide (NPS), had previously been shown to induce only minimal renal effects, having no effect on urine volume, blood urea nitrogen concentration, kidney weight,p‐aminohippurate accumulation or renal morphology. Only an increase in tetraethylammonium uptake has been observed following NPS administration to rats. These effects were not enhanced by reducing aromaticity (N‐cyclohexylsuccinimide (NCS)). Compounds with increased aromaticityN‐(1‐naphthyl)succinimide (NNS),N‐(1‐anthracenyl)succinimide (1‐NAS) andN‐(9‐anthracenyl)succinimide (9‐NAS) — also only weakly affected renal function. However, NNS (1.0 mmol/kg) and, to a lesser degree, 9‐NAS (1.0 mmol/kg) proved to be hepatotoxins. Liver damage was most pronounced near central vein regions of the lobule and least evident around periportal sites. Damaged liver tissue exhibited unusually large deposits of connective tissue and hypertrophied hepatocytes with numerous vacuoles in their cytoplasm. Therefore, derivatives of NPS with increased or decreased aromaticity relative to the parent compound do not exhibit the ability to induce moderate or marked nephrotoxicity. However, increasing aromaticity did produce the derivatives NNS and 9‐NAS, which are hepatotoxins. These compounds represent the first members in this series of compounds

ISSN:0260-437X    

DOI:10.1002/jat.2550090404

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractThe nephrotoxicity ofcis‐platinum (CDDP) in the rat can be controlled throughout a series of weekly administrations of CDDP (each of 5 mg kg−1, i.v.) for at least three weeks by a combination of protective measures involving pretreatment with dithiocarbamates and diuretics and the administration of appropriate dithiocarbamates given 1h after the CDDP. The use of dithiocarbamates with polar substitutents is effective in removing both renal and hepatic deposits of platinum from rats subsequent to its administration and in this respect these compounds are significantly superior to meso‐2,3‐dimercaptosuccinic acid (DMSA) in the rate at which platinum is removed and in the amounts removed. The most effective of the dithiocarbamates remove ca. 70% of the platinum from the kidneys and the liver; the least effective remove ca. 50% of the platinum from these organs when given at a level of 1.57 mmol kg−1i.p. for 6 days subsequent to the administration of CDDP. Acetazolamide was shown to be much less effective in preventing renal damage than the dithiocarbamates and was not effective in reducing renal or hepatic levels of platinum. Pretreatment with sodium diethyldithiocarbamate 12h prior to the administration of the CDDP was more effective in preventing renal damage than the administration of this compound 30 min before thecis‐platinum. Several dithiocarbamates are found to be superior to sodium diethyldithiocarbamate in reducing renal platinum burdens of rats given CDDP at the level of 6 mg kg−1, and dose—response curves for the removal of renal and hepatic platinum were determined for sodiumN‐methyl‐D‐glucamine dithiocarbamate (NaG). The use of dithiocarbamates, other than sodium diethyldithiocarbamate, to control the nephrotoxicity of CDDP may possess some adv

ISSN:0260-437X    

DOI:10.1002/jat.2550090405

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

Abstract3‐Hydroxypropylmercapturic acid [3‐OHPrMCA,S‐(3‐hydroxypropyl)‐N‐acetyl‐‐l‐‐cysteine] was quantitatively measured by high‐performance liquid chromatography (HPLC) in the urine of rats given allylamine‐HCl (5, 25, 50, 100 and 150 mg kg−1), acrolein (13 mg kg−1), allylalcohol (64 mg kg−1), allylchloride (76 mg kg−1), allylbromide (120 mg kg−1), allylcyanide (115 mg) and cyclophosphamide (160 mg kg−1) by gavage in water. 3‐OHPrMCA was measured by HPLC in 24‐h urine collections; the lower detection limit was 1.25 μg or 5.6 nmol ml−1. Various doses of allylamine resulted in 3‐OHPrMCA excretion at a fairly constant percentage of the dose, ca. 44–48% at 0–24 h and 3% at 24–48 h, indicating rapid metabolism through glutathione conjugation in the first 24h. Similarly, 3‐OHPrMCA was recovered in the urine of rats given acrolein (78.5%), allylalcohol (28.3%), allylchloride (21.5%), allylbromide (3.0%), allylcyanide (3.7%) and cyclophosphamide (2.6%). These data indicate that 3‐OHPrMCA can be used as a marker of exposure to allylic and other comp

ISSN:0260-437X    

DOI:10.1002/jat.2550090406

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractTo study the dermal penetration of benzo[a]pyrene (BAP) in relation to other polycyclic aromatic hydrocarbons (PAHs), a complex mixture of PAHs was applied to the backs of CD‐1 mice, and the dermal residence times of BAP and eleven other PAHs were determined using gas chromatography. The dermal penetration of BAP was found to be representative of the other PAHs studied, with a dermal half‐life of 6.7 h. Half‐lives of the other eleven PAHs ranged from 5.0 to 8.8 h. The dermal half‐life of BAP applied in a volatile organic solvent, rather than a PAH mixture, was 3.0 h. The effects of five complex organic mixtures, with boiling points ranging from 300–700°F to>850°F, on the dermal residence time of BAP was studied by adding radiolabeled BAP to the mixtures, and applying them to the backs of mice. All of the mixtures studied increased the dermal residence time of BAP by amounts ranging from 1.8‐fol

ISSN:0260-437X    

DOI:10.1002/jat.2550090407

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractForty‐seven mineral oils were tested for their ability to induce sebaceous gland suppression in female C3H/HeN or CF1 mice. Six groups of five mice were treated with zero, one, two, three, four or six epidermal applications of one or more of three volumes (0.2, 0.1 or 0.05 ml) of the test substance. The sebaceous gland suppression indices were calculated from the total numbers of sebaceous glands and hair follicles in nine sections of treated skin from each mouse. Suppression curves were drawn by plotting the mean suppression indices against the number of applications of each oil sample.The suppression curves were compared with the cutaneous carcinogenic potentials of these mineral oils, assessed by long‐term skin bioassays. All the carcinogenic oil samples induced suppression of sebaceous glands. The non‐carcinogenic samples had no significant suppressant activity. There was a correlation between cutaneous carcinogenic activity and suppressant potential for all tested samples. Results of the suppression tests considered, together with the kinematic viscosities of the test substances, enabled accurate prediction of their cutaneous carcinogenic pote

ISSN:0260-437X    

DOI:10.1002/jat.2550090408

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractFollowing i.p. administration of various doses of 2‐methyl‐4‐chlorophenoxyacetic acid (MCPA), ca. 50% is excreted during a 5‐h diuresis experiment. After i.p. administration of MCPA, virtually no distribution occurs (Vrel= 18% of the body weight). Renal excretion of MCPA can be accelerated by inhibition of its renal tubular reabsorption. The distinct inhibition of renal excretion of MCPA by simultaneous administration of probenecid orp‐aminohippurate (PAH) indicates the active tubular transport of MCPA; this transport process can be stimulated by treatment of rats with triiodothyronine. Active tubular transport of MCPA was confirmed by measurement of MCPA accumulation in renal cortical slices, both under aerobic and anaerobic conditions. Accumulation of MCPA under anaerobic conditions indicates an additional passive uptake and binding of MCPA in kidney tissue in accordance with the high degree of binding to plasma albu

ISSN:0260-437X    

DOI:10.1002/jat.2550090409

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractIn routine inhalation toxicity studies laboratory animals are exposed under dynamic exposure conditions to different steady‐state concentrations of a test compound. The relevant exposure concentration is the analytically determined time‐weighted average concentration in the vicinity of the breathing zone of the animals. If the intended use of a bronchospasmolytic aerosol is taken into account, a non‐steady‐state exposure regimen might be more appropriate. Using this approach local effects of high aerosol concentrations on the respiratory tract were investigated in dogs by daily head/nose‐only exposure for 1 h for 4 weeks. Four groups of four dogs were exposed to 20, 40 and 80 bursts of a bronchodilator formulation using a modified metered dose inhaler. The analytically determined mean concentration of the active ingredient (prostaglandin) in the breathing zone was 43.1, 92.2 and 193.9 μg

ISSN:0260-437X    

DOI:10.1002/jat.2550090410

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY

摘要:

AbstractUnrefined lubricating oils contain relatively high levels of polycyclic aromatic hydrocarbons (PAH) and have been shown to induce tumors in mouse skin. Exxon has developed a new method of refining these materials, a severe hydrotreatment process that is optimized for PAH removal. The specific objectives of the current study were to assess PAH reduction and then to evaluate directly the dermal carcinogenic potential of the materials that spanned the range of products produced by this method.The test samples included unrefined light and heavy vacuum distillates from a naphthenic crude oil, as well as the corresponding severely hydrotreated products. Two sets of samples were prepared to assess the effects of various operating parameters in the reactor. Additionally, positive (benzo[a]pyree), negative (white mineral oil) and vehicle (toluene) control groups were included to assess the sensitivity and specificity of the bioassay. Each sample was applied in twice‐weekly aliquots to the backs of 40 male C3H mice.In the analytical studies, significant reductions in the levels of several specific PAH were demonstrated. In the dermal carcinogenesis studies, the unrefined oils and the positive control induced tumors and also significantly reduced survival. None of the mice treated with severely hydrotreated oils or with the negative or vehicle controls developed skin tumors, and survival of these mice was not significantly different from the control. Thus, the data demonstrated that this new, severe hydrotreatment process was an effective means of converting carcinogenic feedstocks to non‐carcinogenic produ

ISSN:0260-437X    

DOI:10.1002/jat.2550090411

出版商:John Wiley&Sons, Ltd.    

年代:1989

数据来源: WILEY