摘要:

An experimental protocol was designed to assess humoral immune responses in animals antigenically challenged without the aid of adjuvants. The antigen selected was keyhole limpet hemocyanin (KLH). An enzyme‐linked immunosorbent assay (ELISA) was utilized as the technique to measure serum antibody levels. The procedure was tested for sensitivity by use of a known immunosuppressant (cyclophosphamide), two metals (lead and selenium), and three chlorinated hydrocarbons (polychlorinated biphenyls, pentachlorophenol, and toxaphene). KLH without adjuvant provoked an adequate humoral immune response when assessed by the ELISA. The antibody response was greater on d 15 than on d 8 following primary KLH challenge, while secondary challenge resulted in an additional 10‐fold increase in antibody levels. Cyclophosphamide suppressed the later primary response (d 15) and the secondary response more so than the early primary response (d 8). Of the S chemicals tested, 4 resulted in significantly impaired antibody levels to KLH at some time during the response. The magnitude of the immune response elicited to KLH is compared to that reported for bovine serum albumin and ovalbumin administered with Freund's adjuvant.

ISSN:0098-4108    

DOI:10.1080/15287398309530416

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Adult male rats were fed diets containing 0, 5, 15, and 30 ppm chlordecone for 90 d and then either bred to untreated females or sacrificed for terminal studies. Chlordecone residues in liver, fat, and serum were determined in the treated males. Reproductive performance was unaffected, and no histologic changes in the male sex organs could be attributed to chlordecone treatment Reversible decreases in the motility and viability of epldidymal spermatozoa and decreased sperm reserves in the cauda epididymidis were observed in rats fed 15 or 30 ppm. No effect on sperm morphology or on sperm concentration in epididymal fluid was detected. Chlordecone accumulation in tissues was linearly related to dietary levels, with the highest chlordecone concentration occurring in the liver.

ISSN:0098-4108    

DOI:10.1080/15287398309530417

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Preimplantation mouse embryos were exposed to ricin, a plant toxin, in vitro and in vivo. The effect was evaluated by morphological observations of the exposed embryos as well as by means of protein synthesis. Ricin was highly toxic to the preimplantation mouse embryo in vitro, the effect being greater on the 2‐cell than on the 4–8‐cell stage. Intraperitoneal injection of ricin induced a small number of fetuses with exencephaly.

ISSN:0098-4108    

DOI:10.1080/15287398309530418

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The differential disposition of hexachlorocyclopentadiene (HCCP) following oral administration, as contrasted to inhalation or intravenous administration, may account for its lower toxicity by this route. Following an intravenous dose [14C]HCCP to rats at 0.59 mg/kg, 39.0% of the radioactivity remained in the tissues at 72 h; after inhalation of vapors of [14C]HCCP (1.3–1.8 mg/kg), this amount was 71.5%. After oral doses of 4.1 or 61 mg/kg, however, the amount was only 2.4%. No detectable amount of intact HCCP was present in the lungs or kidneys of rats exposed to the chemical by inhalation, and only about 1% was converted to CO2, regardless of the route of administration. The chemical reactivity of HCCP with biological materials was evident in in vitro experiments, in which HCCP became bound to components of whole blood, plasma, liver homogenates, fecal homogenates, and intestinal contents. Thus, the lower toxicity of oral doses of HCCP may be related to its reaction with intestinal contents and its lack of absorption into tissues, in substantial amounts, as the intact, reactive form.

ISSN:0098-4108    

DOI:10.1080/15287398309530419

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Dimethyl sulfoxide (DMSO) suppresses conversion of the prodrug sulindac to its bioactive sulfide metabolite (SD) by competitively inhibiting sulfoxide reductase. During continuous iv infusions of sulindac (1 mg/kg‐h), plasma concentrations of SD at steady‐state equilibrium were 80% lower when DMSO was infused concomitantiy at 0.34 ml/kg‐h, whereas sulindac plasma concentrations were not significantly affected by DMSO. Dermal application and intragastric administration of DMSO also inhibited SD accumulation in plasma. DMSO was only a weak inhibitor of SD oxidation in vitro and did not affect the rate of SD elimination in vivo. In contrast, dimethyl sulfide, a metabolite of DMSO, was a potent inhibitor of SD oxidase in vitro. These data suggest that DMSO can inhibit bioactivation and, hence, the antiinflammatory effects of sulindac.

ISSN:0098-4108    

DOI:10.1080/15287398309530420

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Male and female Sprague‐Dawley rats were treated once with either crude or purified hexachlorobenzene (HCB) or crude or purified hexabromobenzene (HBB) at 150 mg/kg, intraperitoneally. Examination of hepatic microsomes 4 d later revealed an increase in cytochrome P‐450 levels in both HCB‐ and HBB‐pretreated animals. HBB produced a slight but statistically significant hypsochromic shift. Both HCB and HBB produced an increase in benzphetamine N‐dealkylation: HCB produced a greater effect than HBB, and male rat microsomes produced more HCHO than female rat microsomes from the N‐demethylation of benzphetamine. HCB and HBB both enhanced ethoxycoumarin and ethoxyresorufin O‐dealkylation. Liver‐to‐body weight ratios were not significantly affected by pretreatment with either halogenated compound. There appeared to be no difference between the crude and purified halogenated compounds. Electrophoresis of microsomes from male rats pretreated with purified HBB indicated the presence of a band at 53,000 daltons, which was also seen in microsomes from rats pretreated with 3‐methylchotanthrene. This band was absent in microsomes from rats pretreated with phenobarbital. Evidence from other laboratories has demonstrated the mixed type of P‐450(s) induction after HCB administration, as does this report using enzymic and electrophoretic data.

ISSN:0098-4108    

DOI:10.1080/15287398309530421

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Phenylethanol was given at different levels (432, 43, or 4.3 mg/kg) by gavage to pregnant Long‐Evans rats during the “critical period” of organogenesis. Examination of offspring revealed adverse reproductive and teratogenic effects in a dose‐related manner. Intrauterine growth retardation occurred at levels of 432 and 4.3 mg/kg. Embryolethality was 18% at 43 mg/kg and 10% at 4.3 mg/kg. Malformations occurred in the following sequence: 100% at 432 mg/kg; 93% at 43 mg/kg, and 50% at 4.3 mg/kg. Noteworthy dose‐related teratogenic effects of phenylethanol in offspring manifested themselves in increased incidences of malformed eyes, neural‐tube defects, hydronephrosis, and limb defects.

ISSN:0098-4108    

DOI:10.1080/15287398309530422

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The acute intraperitoneal LD50 values of various hydroxychlorodiphenyl ethers (HO‐ClxDPEs; x = 5–7) in mice have been determined. The acute toxicities observed were on the order of, or slightly less than, that observed previously for 2‐hydroxy‐2’,4,4'‐trichlorodiphenyl ether (2‐HO‐CI3‐DPE; irgasan DP‐300; Triclosan), a commonly used bactéricide. However, the acute toxicities determined for these compounds were substantially less than have been observed for HO‐CI,‐DPEs and pentachlorophenol. The HO‐CIxDPEs had a marked hypothermic effect, similar to that produced by 2‐HO‐Cl3‐DPE. Symptomatology following exposure to the HO‐CIx DPEs (x = 5–7) suggested a nonspecific depressant effect on the central nervous system.

ISSN:0098-4108    

DOI:10.1080/15287398309530423

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Five different dose levels of 2‐acetylaminofluorene (2‐AAF) were fed to weanling mice of 4 different genotypes from three unrelated F1hybrids for 13 wk to determine differences in susceptibility to induction of bladder hyperplasia. Differences in the prevalence of hyperplasia per se and in the average grade of hyperplasia were interpreted as indicating greater susceptibility. On this basis, males of all genotypes were more susceptible than females. Among the genotypes, (AEXYS)F1mice (AY) were most susceptible, followed closely by yellowAvy/A(BALB/cXVY)F1mice (CV). Agouti Ali(BALB/cXVY)F1mice were less susceptible than their yellow siblings and similar to the (C57BL/6XC3H)F1mice. Neither body weight gain nor any of the biochemical parameters measured appeared to be affected at any dose level of 2‐AAF. However, quantitative differences in several biochemical characteristics were detected among the genotypes. Serum ?‐glutamyl transpeptidase activity was higher in the A Y mice than in the other hybrids. Among the CV mice, the yellow animals had lower glutathione S‐transferase (GST) activity than their agouti siblings. Hepatic GST activity was lower in CV mice than in either of the other hybrids. Hepatic cytochrome P‐450 and bsactivities were similar in all hybrids.

ISSN:0098-4108    

DOI:10.1080/15287398309530424

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The disposition and metabolism of14C‐labeled 4‐chloro‐2‐nitroaniline (CNA) was studied in male F344 rats following oral or intravenous (iv) administration. The gastrointestinal absorption of CNA was found to be near complete and was not affected by the dose in the range studied (0.788–78.8 μmol/kg). Following either oral or iv administration, CNA was rapidly distributed throughout the tissues and showed no marked affinity for any particular tissue. [14C]CNA was rapidly cleared by metabolism and excretion in urine and to a lesser extent in feces. The whole‐body half‐life of CNA in the rat was approximately 1 h, and clearance of radioactivity from the body was near complete in 3 d. The known carcinogen and potential metabolite of CNA, 4‐chloro‐o‐phenylenediamine, was not detected in rat tissues or excretia following administration of CNA. Approximately 70% of the dose was detected in urine as a sulfate conjugate of a single metabolite of CNA. The remainder of the dose was excreted in the form of seven additional metabolites and a trace of the parent compound. CNA‐derived radioactivity had little potential for bioaccumulation, and there was no evidence for saturation of any mechanism involved in the absorption, distribution, metabolism, or excretion of CNA in the dose range studied.

ISSN:0098-4108    

DOI:10.1080/15287398309530425

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor