摘要:

AbstractThe basis that led to the adoption of the exponent (0.75) as a scaling factor for the relationship between body weight and energy metabolism is presented. In the risk assessment formulation, it may be appropriate to use the 0.75 power of body weight as a scaling factor for carcinogenicity data obtained from animal studies.

ISSN:0260-437X    

DOI:10.1002/jat.2550120503

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractForty‐eight dogs were separated into four groups of six males and six females. Acrolein (0.1% aqueous) was administered in gelatin capsules to three of these groups at dosing levels of 0.1, 0.5 and 1.5 mg kg−1day−1based on results of a range‐finding study. After 4 weeks, the high dose was increased to 2 mg kg−1day−1. The fourth group received deionized water in the same number of gelatin capsules as the high‐dose group. Dosing was 7 days per week for 53 weeks. Blood and biochemical measurements were made pretest and at 3‐month intervals thereafter. At termination, all dogs were subjected to full necropsy and histological exmamination.The major test effect noted was frequent vomiting after dosing. This was observed to be dose‐dependent and the frequency decreased with time, indicating an adaptive effect. One mid‐dose female died during the test and was diagnosed as having died of severe bronchial pneumonia, probably a result of vomitus aspiration. Serum albumin, calcium and total protein values were depressed in high‐dose animals throughout the study. Some variability in red blood cell parameters and coagulation times were noted but the significance of these ef

ISSN:0260-437X    

DOI:10.1002/jat.2550120504

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractA wide variety of chemicals may induce allergic contact dermatitis (contact sensitivity). Some chemical allergens may, in addition, cause respiratory sensitization.Topical exposure of mice to contact and respiratory chemical sensitizers results in the initiation of divergent immune responses characteristic of preferential activation of different functional subpopulations of T helper (TH) cells. In the present study we have sought to make use of these differences, particularly differences in the ability of contact and respiratory allergens to provoke IgE responses, and to question whether opportunities exist for the identification of chemicals with the potential for respiratory sensitization. We have examined alterations in the serum concentration of IgE following topical exposure of mice to seven chemical allergens; trimellitic anhydride (TMA), phthalic anhydride, diphenylmethane‐4,4′‐diisocyanate (MDI), dicyclohexylmethane‐4,4′‐diisocyanate (HMDI), isophorone diisocyanate (IPDI), oxazolone and 2,4‐dinitrochlorobenzene (DNCB). Three of these—TMA, phthalic anhydride and MDI—are known human respiratory sensitizers. The other four—HMDI, IPDI, oxazolone and DNCB—appear not to cause respiratory allergy, or at least have a very limited potential to do so. At the concentrations tested, exposure to all chemicals caused a lymphocyte proliferative response in lymph nodes draining the site of application. However, exposure only to TMA, phthalic anhydride and MDI resulted in a substantial increase in the concentration of serum IgE. Treatment with HMDI and IPDI failed to induce any change in serum IgE concentration. DNCB and oxazolone caused only small and transient elevations of IgE that were considerably less marked than those observed with respiratory sensitizers.These data suggest that it may be possible not only to identify chemical allergens as a function of immune responses induced in mice but also to determine the form that allergic reactions may take. It is proposed that analysis of induced alterations in the serum concentration of IgE may provide a method for the identification of those chemicals that have a significant potential to cause resp

ISSN:0260-437X    

DOI:10.1002/jat.2550120505

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

Abstract2‐Methyl‐5,6‐cyclopentapyrimidine (MCPP, CAS No. 36274–29–0) is a white dusty solid with a powerful lingering odor and is formed as a by‐product in the polymer synthesis of an experimental polymer. The acute toxicity following both oral and inhalation exposures and the effects of repeated inhalation exposures in rats were determined. Mutagenic activity was assessed usingSalmonellaas the indicator organism. The chemical is moderately toxic, with the lethal dose following a single oral administration being 90 mg kg−1. Doses ≧ 130 mg kg−1produced strong convulsions. Excessive salivation, hyperactivity and twitching were seen at 90 mg kg−1and only mild initial weight loss was seen in surviving rats (≦ 60 mg kg). Liver injury was produced at doses as low as 17 (but not at 12) mg kg−1. The material was highly toxic by inhalation, with the approximate lethal concentration in rats following single 4‐h exposures being 9 ppm. Convulsive‐like movements were seen at ≦ 9 ppm (not at 2 ppm). Histological findings suggest that MCPP causes dilation of blood vessels with hyperemia of various organs apparent in rats exposed to 1 ppm and sacrificed 1 or 2 days post‐exposure. No evidence of liver or central nervous system damage was seen. Repeated (nine daily 4‐h exposures) inhalation of 2 ppm MCPP failed to produce any signs of a toxic response. No mutagenic activity was seen. The material needs to be c

ISSN:0260-437X    

DOI:10.1002/jat.2550120506

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe toxicity of eleven calcium antagonists from different chemical families was determined in rat hepatocyte primary cultures. The calcium antagonist potency of the same compounds was also determined in isolated rabbit aortic rings contracted with high K+. The hepatocytotoxicity of the calcium antagonists was not directly linked to blockade of voltage‐operated calcium channels, since there was no correlation between the rank order of hepatotoxicity and that for calcium antagonist potency. The toxicity and calcium antagonist potency of each calcium antagonist examined were used to calculate anin vitrotherapeutic index value for each compound. It was observed that therapeutic indices fell into three distinct groups and we therefore propose that thein vitrotherapeutic index can be used to subclassify the calcium antagonist group of drugs. The proposed classification corresponds very closely with one already suggested by Spedding on pharmacological grounds. In conclusion, the in vitro therapeutic index may provide a useful tool in the characterization and subclassification of novel calcium antagonist compound

ISSN:0260-437X    

DOI:10.1002/jat.2550120507

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractGallium arsenide (GaAs) inhibited, dose dependently, δ‐aminolevulinic acid dehydratase (ALAD) activity in blood (as observed on days 1, 7 and 15), liver and brain (on day 15) after a single oral treatment. Levels of blood zinc protoporphyrin (ZPP) and urinary Δ‐aminolevulinic acid (ALA) excretion were elevated on day 7 and day 15 following exposure to 2000 mg kg−1GaAs. A dose‐dependent increase in blood As contents was observed while blood Ga was detectable only at hig

ISSN:0260-437X    

DOI:10.1002/jat.2550120508

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractMotor and sensory conduction velocities (MCV and SCV), amplitude of the sensory action potential (ASAP) of the tail nerve and parameters of brainstem auditory evoked potentials (BAEP) were studied in male Sprague‐Dawley rats after prolonged inhalation exposure to a commercial isomer mixture of diethylbenzene (DEB mixture) containing 6% 1, 2‐DEB. The MCV, SCV and ASAP were studied in one control group (10 rats) and three groups of 12 rats exposed to 500, 700 or 900 ppm DEB mixture for 6 h daily, 5 days per week, for 18 weeks. Rats used for recording BAEP (one control group and two other groups of 15 rats) were exposed to 600 and 800 ppm DEB mixture. The exposure time was the same.Rats exposed to DEB mixture exhibited a time‐ and concentration‐dependent decrease in MCV, SCV and ASAP and a time‐ and concentration‐dependent increase of both the peak latencies of all BAEP components and the interpeak (I–V

ISSN:0260-437X    

DOI:10.1002/jat.2550120509

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractMale Sprague‐Dawley rats were treated either with 1,2‐diethylbenzene (1,2‐DEB) or its putative active metabolite, 1,2‐diacetylbenzene (1,2‐DAB). Experimental rats and appropriate controls were examined electrophysiologically for brainstem auditory evoked potentials (BAEP). Oral administration of 1,2‐DEB (75 or 100 mg kg−1once a day, 4 days a week, for 8 weeks) and intraperitoneal injection of 1,2‐DAB (10 or 15 mg kg−1once a day, 4 days a week, for 8 weeks) produced time‐ and dose‐dependent increases in the peak latencies of all BAEP components as well as in interpeak (I–V) differences, and a decrease in the amplitudes of all the components. The absolute and interpeak latencies recovered partially during an 8‐week (1,2‐DEB) or a 10‐week (1,2‐DAB) recovery period, whereas there were long‐las

ISSN:0260-437X    

DOI:10.1002/jat.2550120510

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractInvestigations to determine the inhibitory activity on the Ca2+‐transport‐ATPase of human erythrocyte membranes were performed with various compounds of toxicological significance, mostly chlorinated and mainly used as biocides, such as phenol, 4‐chlorophenol. 2,4‐dichlorophenol, 2,6‐dichlorophenol, 3,4‐dichlorophcnol, 2,3,4‐trichlorophenol, 2,3,4,5‐tetrachlorophenol, pentachlorophenol (PCP), captan, folpet, captafol, (+)‐camphene, toxaphene, dichlorodiphenyltrichloroethane (UDT), lindane, endrin, dieldrin, α‐endosulfan, β‐endosulfan, paraquat, diallate, 2,4‐dichlorophenoxyaceticacid (2,4‐D) and 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T).Some of the compounds investigated display an inhibitory effect on the Ca2+‐transport‐ATPase at very low concentrations. Thein vitroresults obtained in this enzyme assay can be correlated directly with the results of otherin vitroassays and with the results ofin vivoinvestigations in different species in whkh an inhibitory effect on various biological functions is observed. Therefore, an inhibitory effect on the Ca2+‐transport‐ATPase indicates a toxic effect of these compounds to cell functions.Since the inhibitory effect of these compounds can be measured rapidly and the enzyme is easy to handle, it might be a useful tool to screen the toxic effects of various compounds on cell function. The aim of the authors was to investigate the usefulness of this screening test system for the characterization of the

ISSN:0260-437X    

DOI:10.1002/jat.2550120511

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY

摘要:

AbstractThe alterations of haematological parameters in albino rats were studied after oral administration of an aqueous extract of silken styles of corn (Zea maizeLinn.) at 50, 100 and 150 mg kg−1daily for 21 days. The following haematological values were significantly reduced on the 7th and 21st day following extract administration: haemoglobin (Hb), red blood corpuscles (RBC), clotting time (CT), mean corpuscular volume (MCV), haematocrit (Ht), serum glucose, blood urea nitrogen (BUN), cholesterol, aspartate transaminase (AST), alanine transaminase (ALT), calcium, total protein, total albumin and total acid phosphatase; and white blood corpuscles (WBC), mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), alkaline phosphatase and creatinine increased. The remaining parameters were not significantly affected, except body weight parameters at the two highest doses.The results emphasize that the biochemical changes caused through aqueous extract of silken styles of corn (Zea maizeLinn.) are not significantly toxic at low and medium doses (50 and 100 mg kg

ISSN:0260-437X    

DOI:10.1002/jat.2550120512

出版商:John Wiley&Sons, Ltd.    

年代:1992

数据来源: WILEY