benzofurans and Abnormalities--Drug-Induced

Topics: Abnormalities, Drug-Induced; Adipose Tissue; Animals; Benzofurans; Dioxins; Environmental Pollutants; Female; Finland; Humans; Infant; Lethal Dose 50; Pregnancy

The controversy about dioxin effects on human health received a great deal of attention recently when the State of Missouri was declared to have a dioxin crisis. However, dioxin and several related chemicals are widespread throughout the world. Cutaneous signs play an important part in evaluating toxicity of dioxin and similar chemicals. Chloracne is the most sensitive indicator of significant dioxin exposure. Porphyria cutanea tarda and hyperpigmentation are other known cutaneous effects, and malignant fibrous histiocytomas of the skin may possibly be associated, although data are inconclusive on this point. The AMC Council on Scientific Affairs recommended that all physicians become familiar with chloracne and other toxic effects of dioxin. Dermatologists, especially, should be aware of the problem and may discover early cases of previously unsuspected exposure to this group of chemicals.

Topics: Abnormalities, Drug-Induced; Animals; Benzofurans; Dibenzofurans, Polychlorinated; Dioxins; Dose-Response Relationship, Drug; Environmental Exposure; Environmental Pollutants; Histiocytoma, Benign Fibrous; Humans; Hydrocarbons, Chlorinated; Lethal Dose 50; Naphthalenes; Pigmentation Disorders; Polybrominated Biphenyls; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Polychloroterphenyl Compounds; Porphyrias; Skin Absorption; Skin Diseases; Skin Neoplasms

During January 10-11, 1978 in Lyon, France, a joint National Institute of Environmental Health Sciences/International Agency for Research on Cancer ad hoc Working Group considered and discussed the feasibility of coordinating epidemiological studies on the long-term hazards associated with the chlorinated dibenzo-p-dioxins and chlorinated dibenzofurans (PCDDs and and PCDFs). Nineteen invited scientists from eight countries presented introductory working papers summarizing the most up-to-date and relevant information available from their individual programs. This report represents the collective views and scientific opinions of the Working Group. The greater part of this document comprises epidemiological studies related to episodes of human exposures. The review begins with a brief section concerning possible routes of human exposure, an overview of the pertinent chemical characteristics, and the salient toxicological properties of the structurally similar PCDDs/PCDFs. The Working Group report ends with recommendations for future activities.

Topics: Abnormalities, Drug-Induced; Accidents, Occupational; Acne Vulgaris; Animals; Benzofurans; Chemical and Drug Induced Liver Injury; Chickens; Dioxins; Female; Guinea Pigs; Haplorhini; Humans; Male; Mice; Occupational Diseases; Polychlorinated Dibenzodioxins; Rats; Structure-Activity Relationship

Topics: Abnormalities, Drug-Induced; Animal Diseases; Animals; Benzofurans; Biphenyl Compounds; Cattle; Cattle Diseases; Chemical and Drug Induced Liver Injury; Chickens; Dermatitis, Occupational; Dioxins; Edema; Environmental Exposure; Herbicides; Humans; Hydrocarbons, Halogenated; Poultry Diseases

According to our earlier study, molar-incisor-hypomineralisation (MIH) was associated with the exposure of a child via mother's milk to polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) in a group of Finnish children born in 1987. Since the levels of PCDD/Fs and PCBs in mother's milk/placenta have remarkably decreased, it was important to find out if an association still exists.. The study group was composed of 167 mothers and their children. Placental samples from the mothers were collected in maternity hospitals in Helsinki and Oulu in 1995--1999 and concentrations of the 17 most toxic PCDD/PCDF and 36 PCB congeners were measured. After 7-10 years the children were examined for MIH and the mothers were interviewed on the duration of breast-feeding.. MIH was found in 24 children (14.4%). The duration of breast-feeding ranged from 0 to 30 months (mean=7.2+/-4.7). WHOPCDD/FTEQ ranged from 2.5 to 39.1 pg/g fat (mean=13.7+/-6.8) and WHOPCBTEQ from 0.7 to 9.8 pg/g fat (mean=2.7+/-1.4). The mean sum of PCDD/Fs was 196+/-105 pg/g fat and that of PCBs was 57.2+/-28.1ng/g fat. The total exposure to PCDD/Fs, which was calculated from the placental concentration (used as a proxy for the milk concentration) and duration of breastfeeding, was not associated with the occurrence or severity of MIH. Neither was the total exposure to PCBs associated with the occurrence or severity of MIH.. At prevailing levels, exposure of a child via placenta/mother's milk to PCDD/Fs and PCBs is not associated with MIH.

Topics: Abnormalities, Drug-Induced; Benzofurans; Breast Feeding; Child; Dental Enamel; Dental Enamel Hypoplasia; Dioxins; Female; Humans; Incisor; Milk, Human; Molar; Placenta; Polychlorinated Biphenyls; Polychlorinated Dibenzodioxins; Pregnancy; Prenatal Exposure Delayed Effects; Teratogens; Time Factors; Tooth Demineralization

Studies of embryo-fetal development in rats were conducted with two 5-lipoxygenase inhibitors. SB-202235 (1,000 mg/kg/day) or SB-210661 (50, 100, or 500 mg/kg/day) was administered orally by gavage to female rats on days 6-17 postcoitus (pc) or days 7-16 pc. SB-202235 (1,000 mg/kg/day) and SB-210661 (100 mg/kg/day) reduced maternal body weight gain for the treatment period by 16% and 21%, respectively, relative to controls. SB-202235 (1,000 mg/kg/day) or SB-210661 (50 or 100 mg/kg/day), did not affect numbers of resorptions, dead or live fetuses/litter, but 500 mg/kg/day of SB-210661 caused 100% embryo lethality. SB-202235 (1,000 mg/kg/day) and SB-210661 (50 and 100 mg/kg/day) reduced fetal body weight by 15-30% and produced extensive cardiovascular malformations, as well as diaphragmatic hernias. SB-210661 also caused thymic abnormalities and cryptorchidism. Cardiovascular defects included abnormalities in aorticopulmonary septation, the aortic arch, pulmonary trunk, and ventricular septal defects are discussed relative to comparable human syndromes of cardiovascular malformation.

Topics: Abnormalities, Drug-Induced; Animals; Aorta, Thoracic; Benzofurans; Cardiovascular System; Cryptorchidism; Embryo Implantation; Enzyme Inhibitors; Esophagus; Female; Fetal Weight; Fetus; Hernia, Diaphragmatic; Lipoxygenase Inhibitors; Male; Maternal-Fetal Exchange; Pregnancy; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Specific Pathogen-Free Organisms; Subclavian Artery; Teratogens; Thymus Gland; Urea; Uterus

Great blue heron hatchlings from colonies in the Strait of Georgia, British Columbia, Canada are being monitored for environmental contaminant exposure and effects by the Canadian Wildlife Service. The contaminants of concern are polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs), primarily derived from kraft pulp mill effluent. The levels of PCDDs and PCDFs in eggs from the most contaminated colonies peaked in 1988 and 1989 and dropped dramatically through 1990 to 1992. Brains of heron hatchlings (taken as eggs from the wild and hatched in the laboratory) were analyzed for gross morphological abnormalities. Brains from highly contaminated colonies (Crofton, British Columbia and University of British Columbia Endowment Lands) in 1988 exhibited a high frequency of intercerebral asymmetry. The frequency of this abnormality decreased in subsequent years as the levels of TCDD and TCDD-TEQs (toxic equivalence factors) decreased. The asymmetry was significantly correlated with the level of TCDD and TCDD-TEQs in eggs taken from the same nest. Yolk-free body weight negatively correlated and the brain somatic index positively correlated with the TCDD level in such pair-matched eggs. These results indicate that gross brain morphology, and specifically intercerebral asymmetry, may be useful as a biomarker for the developmental neurotoxic effects of PCDDs and related chemicals.

Topics: Abnormalities, Drug-Induced; Animals; Animals, Wild; Benzofurans; Birds; Body Weight; Brain; British Columbia; Dibenzofurans, Polychlorinated; Female; Hazardous Waste; Linear Models; Morphogenesis; Organ Size; Ovum; Polychlorinated Dibenzodioxins

The present project assessed the effect of environmental contamination with polychlorinated dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and biphenyls (PCBs) on hepatic microsomal ethoxyresorufin O-deethylase (EROD) activities and morphological parameters in matched double-crested cormorant (Phalacrocorax auritus) hatchlings from egg clutches chosen for chemical analysis. Double-crested cormorant eggs were collected from five colonies across Canada, with differing levels of contamination. Levels of contamination expressed in sum of 2,3,7,8-tetrachlorodibenzo-p-dioxin-toxic equivalents (TCDD-toxic equivalents or TEQ, ng/kg egg; mean +/- SEM) were: Saskatchewan, 250 +/- 50; Chain Islands, 672 +/- 73; Christy Islet, 276 +/- 14; Crofton, 131, n = 1; and Lake Ontario, 1606 +/- 118. In the hatchlings, hepatic EROD activities (pmol/min/mg protein; mean +/- SEM) were: Saskatchewan, 283 +/- 42; Chain Islands, 516 +/- 98; Christy Islet, 564 +/- 91; Crofton, 391 +/- 52; and Lake Ontario, 2250 +/- 156. Hepatic microsomal EROD activity (pmol/min/mg protein) regressed positively on TEQ (r2 = .69; p < .00005; n = 25). Yolk weight (g) regressed negatively on TEQ (r2 = .44; p = .00005). Wing length (mm) regressed negatively on PCB-169 (r2 = .28; p = .007). Monospecific antibodies raised against rat cytochrome P-450 1A1 recognized a protein in the hepatic microsomes of the double-crested cormorant, and also in those of the great blue heron (Ardea herodias), using immunoblotting. The intensity of the stained band increased with increased EROD activity, supporting the assumption that ethoxyresorufin is a suitable substrate for avian cytochrome P-450 1A1. These results validate the use of avian hepatic microsomal EROD activity as an index of cytochrome P-450 1A1 induction by environmental levels of polychlorinated aromatic hydrocarbons and as a useful screening tool to determine the extent of exposure to such chemicals. Furthermore, the induction of cytochrome P-450 1A1 observed in the cormorant indicates that the Ah receptor-mediated process, by which TCDD and related chemicals exert many of their toxicities, has been activated.

Topics: Abnormalities, Drug-Induced; Animals; Benzofurans; Birds; Body Weight; Canada; Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System; Dioxins; Eggs; Microsomes, Liver; Oxidoreductases; Polychlorinated Biphenyls

Topics: Abnormalities, Drug-Induced; Animals; Benzofurans; Body Weight; Bone Development; Embryonic and Fetal Development; Female; Male; Mice; Mice, Inbred ICR; Organ Size; Pregnancy

In the United States, there are about 250 former sites that treated wood with preservatives that are now in need of some degree of remediation. The soil at many of these sites is contaminated with creosote, polycyclic aromatic hydrocarbons (PAHs), polychlorinated dibenzo-p-dioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). This paper compares the results of the current USEPA point estimate (deterministic) approach for predicting the health risks associated with exposure to PCDDs/PCDFs in soil with the results of a probabilistic approach which uses a Monte Carlo analysis. At many of these wood treatment sites the hazard posed by the PAHs, and especially pentachlorophenol, can be much greater than that due to PCDD and PCDFs; however, because at this site the health risk associated with PAHs was deemed negligible by ATSDR, only PCDDs/PCDFs were evaluated. Octachlorodibenzo-p-dioxin (OCDD) and octachlorodibenzofuran (OCDF) congeners were evaluated independently from the other congeners due to their prevalence in the environment and the availability of congener-specific data. The results of the reevaluation of the rodent bioassay data for 2,3,7,8-TCDD were considered in the probability distribution for the cancer potency factor. The authors' analyses indicate that when assessing exposure to soil via inhalation, ingestion, and dermal contact, the current regulatory approach used to estimate the reasonable maximally exposed individual (RMEI) (USEPA, Risk Assessment Guidance for Superfund, Vol. 1, Part A, 1989) can predict risks which are 10- to 100-fold greater than the 95th percentile risk predicted by a Monte Carlo analysis.

Topics: Abnormalities, Drug-Induced; Algorithms; Animals; Benzofurans; Dibenzofurans, Polychlorinated; Dose-Response Relationship, Drug; Environmental Pollution; Female; Humans; Industry; Mice; Monte Carlo Method; Polychlorinated Dibenzodioxins; Pregnancy; Probability; Risk; Soil Pollutants; Structure-Activity Relationship; United States; United States Environmental Protection Agency; Wood

Inhibitors of the arachidonic acid cascade were given to pregnant rats during the critical period for morphogenesis of the external genitalia. Groups treated subcutaneously (s.c.) with 0.1 or 0.25 mg/kg/day of triamcinolone acetonide (TA) on gestational days (GD) 14-19 had male fetuses on GD 20 with moderate decreases in absolute anogenital distance (AGD), but gross and histological examinations revealed no alterations to the genital tubercle (i.e., no hypospadias). The s.c. coadministration of arachidonic acid at 100 mg/kg/day had minimal to no effect on AGD in the TA-exposed groups. No effect on AGD was observed in male fetuses from groups administered aspirin orally at 150 mg/kg/day, and only a 6% decrease was observed in the 300-mg/kg/day group. Neither TA nor aspirin adversely affected AGD of female fetuses. In another study, TA was administered on GD 11-19 at dose levels of 0.05 and 0.1 mg/kg/day, and dams were allowed to deliver. High-dose male offspring examined on postcoitum day (PCD) 23, had moderate decreases in AGD. In both studies with TA, there were also significant decreases in offspring weights. The contribution of the decreased weight to the decrease in absolute AGD was examined by a variety of methods (ratio of AGD to cube root of weight or biparietal distance, comparison to weight-matched controls, and covariance analysis). We conclude that TA caused a specific decrease in AGD on GD 20 that was largely reversed by PCD 23. When examined as adults (8 weeks old), the external genitalia of TA-exposed offspring were normal. Thus, the TA-induced decreases in AGD on GD 20 did not predict irreversible malformation. TA also caused other effects, which included a somewhat flattened genital tubercle and apparently thinned and glossy skin between the tubercle and the anus in both sexes on GD 20 and PCD 23, but not as adults. In addition, there were high pup mortality and high incidences of micrognathia and omphalocele (in the 0.25-mg/kg/day group only). Aspirin at 75 or 150 mg/kg/day and a specific lipoxygenase inhibitor (L-656,224) at 1,000 or 2,000 mg/kg/day were also administered from GD 14 to 19, and no offspring effects were observed. Thus, of the three agents that potentially inhibit the arachidonic acid cascade, only triamcinolone produced moderate effects on rat external genitalia that were largely reversible.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Abnormalities, Drug-Induced; Animals; Arachidonic Acid; Aspirin; Benzofurans; Female; Fetal Death; Genitalia, Male; Gestational Age; Hypospadias; Male; Pregnancy; Rats; Rats, Inbred Strains; Triamcinolone; Weaning

Brominated flame retardants involved in many industrial uses contain polybrominated dibenzo-p-dioxins (PBDDs) and dibenzofurans (PBDFs) as contaminants. The levels of these contaminants can be dramatically increased by combustion. These chemicals are closely related in structure to the polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs), of which 2,3,7,8-tetrachloridibenzo-p-dioxin (TCDD) is the most toxic isomer. TCDD and related PCDFs are potent mouse teratogens inducing cleft palate and hydronephrosis at doses below those at which overt maternal and embryo/fetal toxicity occurs. This study examines the teratogenic effects of 2,3,7,8-tetrabromodibenzo-p-dioxin (TBDD), 2,3,7,8-tetrabromodibenzofuran (TBDF), 1,2,3,7,8-pentabromodibenzofuran (1PeBDF), and 2,3,4,7,8-pentabromodibenzofuran (4PeBDF) in C57BL/6N mice treated on gestation day (gd) 10 and examined on gd 18. Pregnant dams were treated with 0-4000 micrograms of each congener per kilogram body weight in 10 ml corn oil/kg. Dose selection was based on the relative toxicity of the chlorinated isomers. Maternal toxicity and developmental toxicity were assessed, and the hard palate and kidney, the target organs for the teratogenic effects of TCDD and related compounds, were examined for structural abnormalities. While the maternal liver weight increased at all dose levels examined for all four compounds, there was no evidence of any maternal toxicity. Embryo/fetal mortality was increased only at greater than or equal to 500 microgram TBDF/kg, while fetal weight increased in a dose-related manner following exposure to TBDD and TBDF. All compounds produced hydronephrosis (HN) at doses below that at which cleft palate (CP) occurred. The incidence of HN was significantly increased above background levels at the following doses (micrograms/kg): TBDD, 3; TBDF, 25; 1PeBDF, 500; 4PeBDF, 400. The LOELs (micrograms/kg) for CP were: TBDD, 48; TBDF, 200; 1PeBDF, 4000; 4PeBDF, 2400. The cleft palate incidence for all four brominated compounds and TCDD could be fit to a common slope, compatible with the concept that these chemicals all exert their teratogenic effects through a common mechanism. The potency of these chemicals, relative to TCDD as 1 for the induction of cleft palate, is TBDD, 0.24; TBDF, 0.10; 1PeBDF, 0.004; and 4PeBDF, 0.005. Previous studies from our laboratory had determined that the chlorinated dibenzofuran isomers had relative potencies of 0.05 (TCDF), 0.03 (1PeCDF), and 0.09 (4PeC

Topics: Abnormalities, Drug-Induced; Analysis of Variance; Animals; Benzofurans; Cleft Palate; Dioxins; Dose-Response Relationship, Drug; Embryonic and Fetal Development; Female; Flame Retardants; Hydronephrosis; Mice; Mice, Inbred C57BL; Polychlorinated Dibenzodioxins; Pregnancy

6-Methyl-1,3,8-trichlorodibenzofuran (MCDF), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and TCDD plus MCDF were administered to C57BL/6 mice and their effects on several aryl hydrocarbon (Ah) receptor-mediated responses including hepatic microsomal aryl hydrocarbon hydroxylase (AHH) and ethoxyresorufin O-deethylase (EROD) induction, immunotoxicity and teratogenicity were determined. MCDF did not induce hepatic microsomal AHH and EROD at doses up to 500 mumol/kg, however, co-administration of MCDF (50 mumol/kg) with a dose of TCDD which elicited a submaximal induction response (i.e. ED80-100, 15 nmol/kg) resulted in some small but significant inhibition of the induction of hepatic microsomal AHH and EROD (14 and 17%, respectively) compared to that observed with TCDD alone. Co-administration of TCDD and other doses of MCDF (10, 100, 200 or 500 mumol/kg) did not effect the induction response. These results were in contrast to the effectiveness of MCDF as an antagonist of the induction of AHH and EROD by TCDD in the rat (up to 50% inhibition of monooxygenase induction). Administration of MCDF (4, 20 and 40 mumol/kg) to C57BL/6 mice caused some inhibition of the splenic plaque-forming cell response to sheep erythrocytes only at the highest dose (26% decrease); the interaction of MCDF (4, 20 and 40 mumol/kg) and an immunotoxic dose of TCDD (3.7 nmol/kg) resulted in significant protection from the immunotoxic effects of TCDD at the 2 higher dose levels of MCDF. Similarly, MCDF (400 mumol/kg) did not cause cleft palate in mice but at this dose level MCDF afforded some protection from TCDD (20 micrograms/kg)-mediated cleft palate in mice. However, studies utilizing [3H]TCDD suggested that the protective effects may be due to modulation of TCDD reaching the palate in the co-treated animals (MCDF plus TCDD). Although both MCDF and Aroclor 1254 were both weak Ah receptor agonists in C57BL/6 mice, the former compound was much less effective as a TCDD antagonist. The observed species-specific effects for these 2 TCDD antagonists may be related species-dependent differences in receptor structure and receptor-ligand (i.e. agonist or antagonist) interactions.

Topics: Abnormalities, Drug-Induced; Animals; Antibody Formation; Aroclors; Aryl Hydrocarbon Hydroxylases; Benzofurans; Chlorodiphenyl (54% Chlorine); Cytochrome P-450 CYP1A1; Cytochrome P-450 Enzyme System; Dioxins; Enzyme Induction; Male; Mice; Mice, Inbred C57BL; Oxidoreductases; Polychlorinated Dibenzodioxins; Species Specificity

Polychlorinated dibenzofurans (PCDFs) are widespread environmental contaminants which have been detected in human tissues and implicated in several poisoning incidents. Their toxic effects are similar to those observed with other related halogenated aromatic hydrocarbons such as TCDD. The teratogenic effects of three PCDFs, 1,2,3,7,8-pentachlorodibenzofuran (1-PeCDF), 2,3,4,7,8-pentachlorodibenzofuran (4-PeCDF), and 1,2,3,4,7,8-hexachlorodibenzofuran (HCDF), were assessed in C57BL/6N mice. Pregnant mice were exposed on Gestation Days 10-13 to 10 ml corn oil/kg containing PCDFs. The dams were killed on Gestation Day 18 and maternal and fetal toxicity were assessed. All three compounds were highly teratogenic, with very steep and parallel dose-response curves for the two diagnostic indicators of dioxin-like teratogenicity, hydronephrosis, and cleft palate. 4-PeCDF was the most teratogenic with an ED50 of 36 micrograms/kg for cleft palate and 7 micrograms/kg for hydronephrosis. 4-PeCDF was approximately 4 times as potent as 1-PeCDF and 10 times as potent as HCDF. The teratogenic responses occurred at a dose below that where any obvious maternal or fetal toxicity was detected. Thus, these three compounds cause teratogenic responses similar to those seen with TCDD but are only 1/10 to 1/100 as potent.

Topics: Abnormalities, Drug-Induced; Animals; Benzofurans; Body Weight; Cleft Palate; Dibenzofurans, Polychlorinated; Dose-Response Relationship, Drug; Female; Hydronephrosis; Mice; Mice, Inbred C57BL; Polychlorinated Dibenzodioxins; Pregnancy

A series of recombinant inbred strains called BXD [produced from a cross between C57BL/6J (B6) and DBA/2J (D2)] were given single i.p. doses of 0.6 mg/kg 2,3,7, 8-tetrachlorodibenzofuran (TCDBF) on day 12 of gestation. The uteri were examined in late gestation with respect to resorptions and fetal death, and fetal malformations. The strains of the B6-type with respect to Ah-locus (Nos. 5, 6, 8, 11, 12, 14, 16 and 29) that are Ah-responsive, exhibited cleft palates in 80-100% of all fetuses, while hydronephrosis occurred at a rate of 20-70%. These two types of malformation are well recognized from earlier experiments with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and its structural analogues, including TCDBF. In the strains of D2-type with respect to Ah-locus (Nos. 2, 15, 19, 21, 22, 24, and 31), which are Ah-nonresponsive, no cleft palates occurred. One strain (No. 2) had a few (17%) fetuses with hydronephrosis. The frequency of fetal deaths and resorptions were relatively low, but slightly higher among B6-strains than D2-strains. The results indicate an association between the genes producing malformations by TCDBF and the Ah-locus.

Topics: Abnormalities, Drug-Induced; Animals; Benzofurans; Chromosome Mapping; Cleft Palate; Female; Fetal Resorption; Hydronephrosis; Male; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Inbred Strains; Polychlorinated Dibenzodioxins; Pregnancy

2,3,7,8-Tetrachlorodibenzofuran (TCDBF) was administered in single doses (0.1-0.8 mg/kg body weight) intraperitoneally to pregnant C57BL mice on d 10, 11, 12, or 13 of gestation. A dose-dependent increase was observed in the frequency of fetal resorptions and fetal death, especially in the earlier stages (d 10-11). Cleft palate and hydronephrosis as well appeared in a dose-dependent manner, with a peak in sensitivity after administration on d 11-12. TCDBF given at a dose level of 0.1 mg/kg body weight on d 12 of gestation (only dose- and stage-tested) produced a marked thymic hypoplasia as well. A few cases of general hydrops occurred. The pattern of malformations and time of sensitivity corresponded well to that observed earlier after administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD; ED50 approximately equal to 25 micrograms/kg) and 3,3',4,4'-tetrachloroazoxybenzene (TCAOB; ED50 approximately equal to 6 mg/kg), two congeners of TCDBF, indicating common mechanisms of action of this family of compounds. Ornithine decarboxylase (ODC) is an important enzyme in cell proliferation and growth with a high activity in embryonic tissues. Liver ODC activity has previously been found to be stimulated by TCDD in weaning mice. However, this enzyme was not found to be stimulated in fetal and placental tissues, but slightly in maternal kidney after treatment with TCDBF in teratogenic doses. It is possible that the ODC activity increases under certain conditions only, on administration of TCDD and its congeners.

Topics: Abnormalities, Drug-Induced; Animals; Benzofurans; Dose-Response Relationship, Drug; Environmental Pollutants; Female; Fetus; Mice; Mice, Inbred C57BL; Ornithine Decarboxylase; Polychlorinated Dibenzodioxins; Pregnancy

Treatment of pregnant C57BL/6N mice with 2,3,7,8-tetrachlorodibenzofuran (TCDF) (0, 250, 500, and 1000 micrograms/kg on gestation day 10 or 0, 10, 30, 50, and 100 micrograms/kg on gestation days 10-13) results in dose-related increases in isolated cleft palates and hydronephrotic kidneys in the offspring. TCDF is teratogenic in 100% of the fetuses at dose levels that are not maternally toxic. The fetal kidney is the most sensitive target organ but the kidney lesions may be reversible.

Topics: Abnormalities, Drug-Induced; Animals; Benzofurans; Cleft Palate; Female; Fetal Death; Gestational Age; Hydronephrosis; Maternal-Fetal Exchange; Mice; Mice, Inbred C57BL; Pregnancy; Teratogens

1 The minimum toxic dose of tetrachloro-dibenzo-p-dioxin (TCDD) for man has been calculated from monkey and human data to be 0.1 microgram kg-1. 2 The amount of TCDD which man takes in from his environment is about 1/2050 of that present in one square metre of his immediate environment. 3 The average concentration of TCDD present in Vietnam immediately after spraying Agent Orange was 8 microgram m-2. 4 A soldier directly sprayed would attain an internal body concentration of 7 X 10(-5) microgram kg-1 or 1/1750 of the minimum toxic dose; soldiers moving through previously sprayed areas would ingest much less. 5 These quantitative aspects indicate that the dioxin sprayed with Agent Orange in Vietnam cannot have caused systemic illnesses in Vietnam veterans or birth defects in their children.

Topics: 2,4-Dichlorophenoxyacetic Acid; 2,4,5-Trichlorophenoxyacetic Acid; Abnormalities, Drug-Induced; Agent Orange; Animals; Benzofurans; Dioxins; Environmental Pollutants; Female; Food Contamination; Herbicides; Humans; Male; Polychlorinated Dibenzodioxins; Pregnancy; Soil Pollutants; Vietnam

Topics: 2,4,5-Trichlorophenoxyacetic Acid; Abnormalities, Drug-Induced; Animals; Benzofurans; Chickens; Chromatography, Gas; Congresses as Topic; Dioxins; Dose-Response Relationship, Drug; Edema; Electron Spin Resonance Spectroscopy; Environmental Exposure; Environmental Health; Humans; Liver; Poultry Diseases; Spectrum Analysis; Structure-Activity Relationship; United States