摘要:

AbstractStudies were conducted to examine acute hepatic and renal toxicity of dichlorobenzene (DCB) structural isomers. Male Fischer 344 (F344) rats were injected with 2, 3 or 4 mmol kg−1of 1,2‐DCB, 1,3‐DCB or 1,4‐DCB (o−, m−, p−). Pair‐fed control (PFC) animals were injected (i.p.) with corn oil (1 ml kg−1). Hepatic and renal toxicity was quantitated 24 h after injection of DCB or vehicle. Plasma transaminase (ALT/GPT) activity was increased (P<0.05) by 1,2‐DCB as a function of dose administered. Centrilobular necrosis was observed in rats treated with 1,2‐DCB while morphology was relatively normal in rats treated withm‐ orp‐DCB. Administration of (2 or 4 mmol kg−1) 1,3‐DCB or 1,4‐DCB did not alter kidney weight or blood urea nitrogen (BUN) levels. Renal cortical slice accumulation ofp‐aminohippurate (PAH) was decreased (P<0.05) by (2 and 4 mmol kg−1) 1,3‐DCB and (3 and 4 mmol kg−1) 1,2‐DCB while accumulation of the cation tetraethylammonium (TEA) was decreased by 4 mmol kg−11,4‐DCB. (TEA). The results of these studies demonstrated thatorthosubstitution enhanced hepatic and renal toxicity. The results also would suggest that the liver was mo

ISSN:0260-437X    

DOI:10.1002/jat.2550130103

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractBrain mitochondrial cytochrome oxidase and respiratory activities were compared afterin vivoandin vitroexposure to cyanide. For thein vivostudies, mice were exposed to a non‐lethal (4 mg kg−1) or lethal (20 mg kg−1) dose of KCN. From these mice, purified brain mitochondria were prepared and cytochrome oxidase and respiratory activities measured. Results of these experiments revealed greater inhibition of cytochrome oxidase activity following a lethal (20 mg kg−1) than a non‐lethal (4 mg kg−1) KCN dose (57 and 45% inhibition, respectively). Respiration states 3 and 4 of brain mitochondria prepared from mice that received 4 mg kg−1KCN were inhibted by 15 and 20%, respectively. In mice that received a lethal 20 mg kg−1KCN dose, respiration states 3 and 4 were each inhibited by ca. 30% (P50% inhibition of mitochondrial cytochrome oxidase activity, these findings suggest that a large proportion of cytochrome oxidase activity may be functional reserve and that cyanide poisoning likely involves other mechanisms in addition to

ISSN:0260-437X    

DOI:10.1002/jat.2550130104

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractSubcutaneous administration of the LD50dose of methyl isocyanate (MIC) to rats induced severe hyperglycaemia, lactic acidosis and uraemia in rats. Neither methylamine (MA) nor N,N′‐dimethylurea (DMU), the hydrolysis products of MIC, administered in equimolar doses had any influence on these parameters except for a marginal transient increase in plasma urea by DMU. Methyl isocyanate administration led to haemoconcentration, resulting in an increase in the plasma concentration of total proteins and a decrease in both the plasma concentration of albumin and the plasma cholinesterase activity. The hydrolysis products of MIC had no influence on any of these parameters. Thus, it seems reasonable to suggest that the systemic effects of MIC are caused by MICper se, in spite of its high hydrolytic instabil

ISSN:0260-437X    

DOI:10.1002/jat.2550130105

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractMale Sprague Dawley rats with cannulated bile duct (BDC rats) received 100 or 200 mg kg−1labelled hexachloro‐1,3‐butadiene ([14C]HCBD) by gavage 1 h (BDC1, rats) or 24 h (BDC24rats) after surgical cannula implantation. Twenty‐four hours after treatment with HCBD, rats were examined histochemically and biochemically for kidney damage. Urine, faeces, liver and kidney radioactivities were also measured in 24‐h samples. Results were compared with those obtained from non‐cannulated (NC) rats. Bile‐duct cannulation did not completely protect against HCBD‐induced kidney damage. The 24‐h [14C] urinary excretion and tissue content was 30–50% lower in BDC rats compared to NC rats and correlated well with the toxicity findings.BDC1rats appeared to be much more resistant to HCBD treatment than BDC24rats. Since faecal [14C] radioactivity extractible by diethyl ether at neutral pH in BDC1, rats was twice that measured in BDC24rats, the greater resistance was attributed to a higher deficiency in the gastrointestinal absorption of unchanged HCBD.The present results reveal that the biliary metabolites of HCBD are not solely responsible for kidney toxicity as previously assumed. They suggest a sinusoidal efflux of the HCBD conjug

ISSN:0260-437X    

DOI:10.1002/jat.2550130106

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractTritium‐labelled benzo[a]pyrene ([3H]BaP) was applied to mouse skin in acetone or mineral oils of differing viscosity. Epidermal DNA and protein were extracted after 24 or 48 h and the degree of adduct formation determined by the radioactivity present.When [3H]BaP was applied in acetone, the degree of DNA and protein binding was around 15–20 times greater than that observed when a low‐viscosity oil was used as a vehicle. When applied in oils of differing viscosity, however, only a twofold difference was seen across the whole viscosity range (13.5 cStSt = stokes, a unit of kinematic viscosity (10−4m2s−1)at 40°C to 1665 cSt at 60°C). From measurements made of urine and fecal radioactivity and from small‐scale investigations using other routes of administration, it was clear that the grooming activity of the animals had a marked effect on skin absorption and macromolecular binding. It is possible that greater grooming activity with low‐viscosity oils may explain why oil viscosity did not have a greater effect on binding levels, but further studies are needed to investigate this.These findings may have important implications in the interpretation of long‐term skin painting studies and may assist in the interpretation of analytical data and short‐ter

ISSN:0260-437X    

DOI:10.1002/jat.2550130107

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe effect of different doses of methyl isocyanate (MIC), carbaryl and thiram on liver microsomal mixed‐function oxygenases (MFO) was studied in adult Swiss Portan mice by intraperitoneal (i.p.) injection for different durations. TheLD50dose of all three toxicants after 0.75 h of administration could increase cytochrome P‐450 and cytochromeb5contents (82–143%), and the 1/4LD50of these compounds could elicit the same effect after 168 h (168–393%). The 1/4LD50dose of thiram decreased the cytochrome P‐450 content below the control level (69.62%) in 0.75 h and the same dose of MIC could decrease the cytochrome P‐450 level by 40% compared to the control after 3 days of consecutive injection. The activities of drug‐metabolizing enzymes (aminopyrine demethylase—NADH and NADPH‐linked—and aniline hydroxylase) were found to increase with all three compounds in general. Marked changes in the activity of the marker enzyme glucose‐6‐phosphatase were also seen after i.p. injection if MIC, carbaryl and thiram. These findings suggested that these compounds were hepatotoxic, which could be due to the

ISSN:0260-437X    

DOI:10.1002/jat.2550130108

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractThiobencarb (S‐(4‐chlorobenzyl)‐N,N‐diethyl thiol carbamate), a dithiocarbamate herbicide, was found to cause neuronal dysfunction in adult and neonate albino rats. In general, organocarbamates exert their action by inhibiting acetylcholinesterase (AChE) activity. Thiobencarb inhibited both acetylcholinesterase and adenosine triphosphatase (ATPase) activities in rat brain. Withdrawal of thiobencarb treatment resulted in the recovery of AChE activity to a normal level, whereas there was no recovery of Na+–K+‐ATPase activity in either neonate or adult rat brains. The results suggest that neuronal dysfunction caused by thiobencarb is mainly due to the inhibition of ATPase activity rather than to the inhibition of AC

ISSN:0260-437X    

DOI:10.1002/jat.2550130109

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractClearance methods were used to clarify the renal handling of calcium (Ca) and phosphorus (P) in a population with renal dysfunction induced by exposure to environmental cadmium (Cd). Seventy‐six Cd‐exposed subjects (32 men and 44 women) and 36 non‐exposed subjects (18 men and 18 womén) took part in this study.Fractional excretion of P was higher in the Cd‐exposed subjects than in the non‐exposed subjects, while that of Ca was equal to that of the non‐exposed subjects. The urinary excretion rates of Ca and P tended to be lower in the Cd‐exposed subjects than in the non‐exposed subjects. The urinary excretion rate of Ca was closely related to creatinine clearance, while that of P was related to creatinine clearance and the percentage tubular reabsorption of phosphorus. It is thought that in Cd‐induced renal dysfunction the urinary excretion of Ca depends on glomerular function, and no increased excretion of urinary Ca was observed by these clearance methods.It is also clarified that the parallelism in the urinary excretion of Ca and Na persists in Cd‐exposed subjects wi

ISSN:0260-437X    

DOI:10.1002/jat.2550130110

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

Abstract7.5% Hypertonic saline–6% Dextran‐70 (HSD) is currently being evaluated in our laboratory as a resuscitation solution for the treatment of hypovolemia at a dose of 4 ml kg−1body weight. A few reports of dextran toxicity, particularly of the kidney, have been cited in the literature, so the present study evaluated the acute and subacute toxicity of HSD administered i.v. to beagle dogs. In the acute toxicity studies animals were infused with a single dose of HSD, or its components of hypertonic saline (HS) or Dextran‐70 (D‐70), at the maximum tolerated dose (MTD: 20 ml kg−1). Controls received Ringers lactate (RL). In the HSD‐infused dogs, transient but significant increases in serum alanine (ala) aminotransferase (AT), aspartate (asp) AT and alkaline phosphatase (AP) were observed for the first 72 h. In most cases this increase was also observed in the HS group. In the subacute studies, dogs were infused daily with the MTD of the above test solutions. Serum ala AT activity was 2–3‐fold higher in the HSD than the RL group for the first 3 days. Again, a similar effect was observed in the HS group. Slight, transient increases in asp AT and AP activity were also observed in the HSD group. Higher lactate dehydrogenase (LDH) activity was only observed at Day 14 in dogs infused with the MTD of HSD or HS. In both studies, no adverse effects on blood urea nitrogen (BUN) or serum creatinine were observed and other transient changes in serum parameters were attributable to hemodilution induced by HSD. No gross or microscopic lesions were observed in any major organ. Considering that the proposed therapeutic dose of HSD is only 4 ml kg−1, it appears that its use should be associated with minimal or

ISSN:0260-437X    

DOI:10.1002/jat.2550130111

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY

摘要:

AbstractLubricant base oils are petroleum products that are predominantly derived from the vacuum distillation of crude oil. Various types of refinement can be employed during the manufacturing process, and evidence suggests that certain of the associated process streams produce skin cancer. Polycyclic aromatic compounds (PACs), some of which are considered as the causative agents, are removed, concentrated or chemically converted during the refinement process. In order to understand the effects of various types of refinement processes on carcinogenic potential, 94 oils were evaluated in the mouse epidermal cancer bioassay. This Exxon database is unique, because of the wide range of crude oils and processing histories represented. Seven processing history classifications are described, and conclusions concerning the impacts of each refinement process on dermal carcinogenicity are discussed.This research also included an evaluation of selected biological and chemical test methods for predicting carcinogenic potential. These included a modified version of the Ames test for mutagenicity, as well as analytical characterizations of the polycyclic aromatic structures in the oils. For classification purposes, a sample was considered to be carcinogenic if it resulted in the production of two or more tumor‐bearing animals (in test groups of either 40 or 50 animals). The modified Ames test was considered to be positive if the mutagenicity index was ≥ 2.0, and PAC analyses were similarly designated as positive or negative according to proposed guidelines. All of the alternative test methods showed similar agreement with dermal carcinogenicity bioassay data; concordance values were ≥ 80%. However, each test was incorrect in ca. 10%–20% of the cases evaluated. Thus, while these methods may have great value as screening tests, the results should not be used in preference to dermal carcinogenicity data for hazard identification or labeling p

ISSN:0260-437X    

DOI:10.1002/jat.2550130112

出版商:John Wiley&Sons, Ltd.    

年代:1993

数据来源: WILEY