摘要:

For 59 chemical compounds, we have found homogeneous data on transformation in vitro, mutagenicity in the Ames test, and carcinogenicity. We have compared the potency in inducing transformation in vitro in hamster fibroblast cells with the carcinogenic potency and found a modest correlation coefficient between the two parameters (T=0.37). For these same 59 compounds it was also possible to compare mutagenic potency in the Ames test with carcinogenic potency. The correlation level was very similar (r = 0.34). The predictivity of transformation in vitro increased significantly when only compounds for which some kind of dose‐response relationship was available were utilized (x = 0.65). This result stresses the importance of the quantitative aspect of the response in predictivity studies. The present study is compared with previous studies on the quantitative predictivity of different short‐term tests. Our work is not definitive, but gives an idea of the possible type of approach to the problem of comparing quantitative predictivities.

ISSN:0098-4108    

DOI:10.1080/15287398309530444

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The objectives of this study were to determine the dermal absorption, systemic elimination, and dermal wash efficiency for polychlorinated blphenyls (PCBs).14C‐Labeled 42% PCB and14C‐labeled 54% PCB were topically and parenterally administered to rhesus monkeys and guinea pigs. Dermal absorption, determined by14C urinary excretion, was extensive. In guinea pigs, 33% of the applied14C‐labeled 42% PCB dose and 56% of the14C‐labeled 54% PCB dose were absorbed. In rhesus monkeys, 15–34% of the labeled 42% PCB was dermally absorbed, depending on the magnitude of the applied dose.

ISSN:0098-4108    

DOI:10.1080/15287398309530445

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Distribution of14C‐labeled 2,4’,5‐trichlorobiphenyl 2,2’,4,4’,5,5'‐hexachlorobiphenyl, and 2,2’,3,3'4,4’,5,6'‐octachlorobiphenyl was studied in the hematopoietic tissues of squirrel monkey and mice (C67 BI) using whole‐body autoradiography. An accumulation of radioactivity was seen in the bone marrow of monkey 24 h and 48 h after iv injection of hexachlorobiphenyl and trichlorobiphenyl, respectively. High concentration of radioactivity was also observed in the bone marrow of normal mice injected iv with octachlorobiphenyl. A combination of whole‐body autoradiography and spleen‐colony assay in supralethally irradiated mice implanted with syngeneic bone‐marrow cells indicated the major part of radioactivity to be localized outside the bone‐marrow hemic compartment, probably in the fat. No effect of hexachlorobiphenyl but a significant inhibition with octachlorobiphenyl (10−5M) and especially trichlorobiphenyl (10−5M) was seen on the formation of granulocytic colonies from mouse progenitor cellsin vitro.

ISSN:0098-4108    

DOI:10.1080/15287398309530446

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Forty‐two male rats were injected with a single intraperitoneal dose of TCDD in acetone and corn oil and sacrificed after 2, 4, 8, 16, 24, and 32 weeks, to study the long‐term effects of a single injection. The liver lesions become progressively worse up to the 16th week and appear thereafter to slowly regress.

ISSN:0098-4108    

DOI:10.1080/15287398309530447

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The toxicity of 2,3,7,8‐tetrachlorodibenzofuran (TCDF) was studied in male Hartley guinea pigs after single or multiple oral treatment. In each animal studied, adipose tissue, liver, and skin were the major depots of TCDF and accounted for 50–74% of the total dose. The whole‐body half‐life of TCDF in guinea pigs was estimated to be approximately 40 d. This slow clearance of TCDF by guinea pigs may explain the high toxicity of TCDF for this species even when very low repeated doses were administered. Intervals of 1, 2, or 4 wk between doses had little effect on TCDF iethality, but did have an effect on the pattern of toxicity. Treatment of mature animals with high single doses of TCDF (10 or 15 μg/kg body weight) resulted in the immediate loss of weight and the eventual death of all treated animals within 2–4 wk after the loss of approximately 35% of their initial body weight. Treatment of immature animals with low multiple doses totaling cumulative doses of between 4 and 12 μg/kg resulted in the death of 75% of these animals, with the deaths occurring between 7 and 19 d after the initial appearance of quantitative toxic symptoms (loss of weight); however, weight loss was less dramatic following repeated low doses than after acute high doses. Concentration of TCDF in adipose tissue was generally proportional to dose of TCDF. With increasing time after dosage, there was a shift in distribution from adipose tissue to liver.

ISSN:0098-4108    

DOI:10.1080/15287398309530448

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Hexabromonaphthalene (HBN) has been identified as a toxic contaminant of Fire‐master BP‐6, a mixture of polybrominated biphenyls (PBBs) that is used commercially as a fire retardant and that was responsible for a major public health emergency in Michigan in 1974. Previously reported to be a single compound, the hexabrominated naphthalene derived from direct bromination of naphthalene was here shown by high‐field nuclear magnetic resonance (NMR) to be a mixture of two closely related isomers, 1,2,3,4,6,7‐HBN and 2,3,4,5,6,7‐HBN, in a ratio of 60:40. The absorption, distribution, metabolism, and excretion of the HBN mixture was studied in the male Fischer‐344 rat. [14C] HBN was incompletely absorbed after oral doses of 0.4 and 4.0 μmol/kg body weight After iv treatment, fecal excretion accounted for 24% of the total dose by the end of d 1, 44% by d 3, and 62% by d 35. Urinary excretion was negligible. The excreted radioactivity was in the form of metabolite(s). Biliary excretion studies confirmed the nature of the excreted dose. The tissue distribution pattern showed accumulation and redistribution during early time points (0.5–3 h). By the end of the first day, 30.7% and 12.3% of the total dose remained in the liver and fat, respectively. All other tissues accounted for less than 5% of the total dose by d 1. The major tissue depots remained liver and adipose tissue, which contained 26% and 4.6% of the total dose, respectively, by d 35. This residual radioactivity was found to be unmetabolized HBN. Thus, over 60% of the dose of HBN is readily metabolized and excreted and was tentatively identified with the toxic isomer 1,2,3,4,6,7‐HBN. The remainder, probably 2,3,4,5,6,7‐HBN, was relatively nontoxic and extremely persistent, with the liver being the primary site of long‐term accumulation.

ISSN:0098-4108    

DOI:10.1080/15287398309530449

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Ten pyrethroids affected binding of [3H]perhydrohistrionicotoxin ([3H]H12‐HTX) to the channel sites of the nicotinic acetylcholine (ACh) receptor/channel of the electric organ of the electric ray,Torpedo ocellata, and inhibited45Ca2+flux through the receptor's ionic channel. Most pyrethroids stimulated binding of [3H]H12‐HTX to the channel sites in 30 s, in absence of carbamylcholine, with little or no effect on binding of [3H]ACh to the receptor sites, which suggests that the pyrethroids are binding to a third kind of site. However, in presence of carbamylcholine, all pyrethroids inhibited binding of [3H]H12‐HTX, with esters of cyclopentenolone more potent, and generally more rapid in doing so, than esters of α‐cyano‐3‐phenoxybenzyl alcohol. Changes in the acidic moiety of the pyrethroid had little effect. Kadethrin, whose alcohol moiety is 5‐benzyl‐3‐furylmethyl, was the most potent pyrethroid in stimulating [3H]H12‐HTX binding (in absence of carbamylcholine) in 30 s (18‐fold) and in inhibiting it in 120 min. The pyrethroids were more potent in their modulation of [3H]H12‐HTX binding at lower temperatures. Inhibition of receptor binding and receptor‐regulated ion transport by concentrations of pyrethroids similar to those at which they affect nerve conduction suggests that the nicotinic ACh receptor may be an additional target for the toxic action of pyrethroids.

ISSN:0098-4108    

DOI:10.1080/15287398309530450

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The effect of atropine, 2‐pyridine aldoxime methiodide (2‐PAM), and several O,O,O‐tri‐alkylphosphorothioates on poisoning of rats by a series of O,O‐dimethyl and O,O‐diethyl S‐alkyl phosphorothioates was investigated. Atropine and 2‐PAM successfully protected rats treated with O,O‐diethyl S‐n‐propyl and S‐i‐propyl phosphorothioates, while the O,O,O‐trialkyl phosphorothioates were effective in protecting rats treated with O,O‐dimethyl S‐methyl and S‐ethyl phosphorothioates. O,O‐Dimethyl and O,O‐diethyl S‐i‐propyl phosphorothioates also were examined forin vitroandin vivoinhibition of rat plasma, red blood cell, and brain cholinesterase. Overall, the results indicated that two different mechanisms, cholinergic and noncholinergic, are involved in intoxication by the O,O,S‐trialkyl phosphorothioates.

ISSN:0098-4108    

DOI:10.1080/15287398309530451

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

The storage and metabolism of lindane (γ‐HCH) was studied in the female rat after the administration of a hepatotoxic dose of chlorobenzene. Impaired lindane metabolism was observed following a challenge dose of 1.12 g chlorobenzene/kg. The data indicated that a hepatotoxic dose of chlorobenzene (CB) selectively impaired certain pathways, such as dehydrochlorination and the direct hydroxylation of lindane, to a greater extent than others, such as the dehydrogenation and dechlorination of lindane. Pretreatment with a subtoxic level of chlorobenzene produced: (1) significant increases in the dehydrogenation of lindane, (2) significant increase in the excretion of conjugated metabolites, (3) significant increases in the excretion of metabolites derived from the dehydrogenation of lindane through hexachlorocylohexene, γ‐HCCH, (4) significant improvement in the excretion of metabolites derived from CB‐impaired dehydrochlorination of lindane as well as from the CB‐impaired hydroxylation of lindane, and (S) significant reduction in the level of unaltered lindane stored in the adipose tissue. Repeated pretreatment with a subtoxic level of chlorobenzene offered significant protection against the reduction in lindane metabolism produced by the single hepatotoxic dose of chlorobenzene. Pretreatment with γ‐HCH alone was not as effective against the hepatotoxic effect of CB on lindane metabolism.

ISSN:0098-4108    

DOI:10.1080/15287398309530452

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor

摘要:

Oxychlordane reached lethal levels in birds given dietary dosages of HCS‐3260 (70.75% cis‐chlordane and 23.51% trans‐chlordane) at 6 levels from 50 to 500 ppm. Oxychlordane ranged from 9.4 to 22. 1 ppm in brains of cowbirds (Molothrus ater), grackles (Quiscalus quiscula), and red‐winged blackbirds (Agelaius phoeniceus) that died on dosage and from 1.3 to 4.8 ppm in sacrificed birds, providing a clear diagnostic separation. Among starlings (Sturnus vulgaris), however, oxychlordane ranged from 5.0 to 19.1 ppm in brains of birds that died, significantly lower than in the other species, and from 1.4 to 10.5 ppm in sacrificed birds, overlapping the levels in those that died. Lethal levels, therefore, begin near 5.0 ppm, as in a previous study in which oxychlordane itself was fed, but the data from starlings emphasizes the need for confirmatory necropsy findings in diagnosis of poisoning.

ISSN:0098-4108    

DOI:10.1080/15287398309530453

出版商:Taylor & Francis Group    

年代:1983

数据来源: Taylor