In vitro human cell-based TTR-TRß CALUX assay indicates thyroid hormone transport disruption of short-chain, medium-chain, and long-chain chlorinated paraffins.

Over the last decades, short-chain chlorinated paraffins (SCCPs), medium-chain chlorinated paraffins (MCCPs), and long-chain chlorinated paraffins (LCCPs) have become the most heavily produced monomeric organohalogen compound class of environmental concern. However, knowledge about their toxicology is still scarce, although SCCPs were shown to have effects on the thyroid hormone system. The lack of data in the case of MCCPs and LCCPs and the structural similarity with perfluoroalkyl substances (PFAS) prompted us to test CPs in the novel TTR-TR CALUX assay for their thyroid hormone transport disrupting potential. Four self-synthesized and additionally purified single chain length CP mixtures (C10-CPs, C11-CPs, C14-CPs and C16-CPs) and two each of industrial MCCP and LCCP products were tested in parallel with PFOA. All CP mixtures influenced the TTR binding of T4, giving activities of 1,300 to 17,000 µg/g PFOA equivalents and lowest observable effect concentrations (LOELs) of 0.95 to 0.029 mM/L incubate. Highest activities and lowest LOELs were observed for C16-CPs (48.3% Cl content, activity 17,000, LOEL 0.047 mM/L) and a LCCP mixture (71.7% Cl content; activity 10,000; LOEL 0.029 mM/L). A trend of higher activities and lower LOELs towards longer chains and higher chlorination degrees was implied, but could not be statistically confirmed. Irrespectively, the less well examined and current-use LCCPs showed the highest response in the TTR-TRß CALUX assay.

Dialkylcarbamoyl chloride (DACC)-coated dressings in the management and prevention of wound infection: a systematic review.

OBJECTIVE: Dialkylcarbomoyl chloride (DACC)-coated dressings (Leukomed Sorbact and Cutimed Sorbact) irreversibly bind bacteria at the wound surface that are then removed when the dressing is changed. They are a recent addition to the wound care professional's armamentarium and have been used in a variety of acute and chronic wounds. This systematic review aims to assess the evidence supporting the use of DACC-coated dressings in the clinical environment. METHOD: We included all reports of the clinical use of DACC-coated dressings in relation to wound infection. Medline, Embase, CENTRAL and CINAHL databases were searched to September 2016 for studies evaluating the role of DACC-coated dressings in preventing or managing wound infections. RESULTS: We identified 17 studies with a total of 3408 patients which were included in this review. The DACC-coating was suggested to reduce postoperative surgical site infection rates and result in chronic wounds that subjectively looked cleaner and had less bacterial load on microbiological assessments. CONCLUSION: Existing evidence for DACC-coated dressings in managing chronic wounds or as a surgical site infection (SSI) prophylaxis is limited but encouraging with evidence in support of DACC-coated dressings preventing and treating infection without adverse effects.

Responses of mouse liver to dechlorane plus exposure by integrative transcriptomic and metabonomic studies.

Dechlorane plus (DP), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for DP have seldom been reported. In the present study, we investigated hepatic oxidative stress, DNA damage, and transcriptomic and metabonomic responses of male mice administered 500 mg/kg, 2000 mg/kg, and 5000 mg/kg of DP by gavage for 10 days. The results showed that DP exposure increased the level of superoxide dismutase (SOD) and 8-hydroxy-2-deoxyguanosine (8-OHdG). The microarray-based transcriptomic results demonstrated that DP exposure led to significant alteration of gene expression involved in carbohydrate, lipid, nucleotide, and energy metabolism, as well as signal transduction processes. The NMR-based metabonomic analyses corroborated these results showing changes of metabolites associated with the above altered mechanisms. Our results demonstrate that an oral exposure to DP can induce hepatic oxidative damage and perturbations of metabolism and signal transduction. These observations provide novel insight into toxicological effects and mechanisms of action of DP at the transcriptomic and metabonomic levels.

Endocrine disruption and ovarian morphometric responses in rats following exposure to tetradifon.

We have investigated whether exposure to tetradifon causes ovary injuries, disrupts folliculogenesis in rat and whether ovary hormones (estrogen and progesterone) to be affected by this endocrine-active agent. Female rats were exposed orally to a dose of 28.9 mg/kg/day for 6 or 12 weeks. After sacrifice, ovary glands were examined for morphometric changes. The serums were used to determine levels of 17beta-estradiol and progesterone. Results showed no sign of toxicity. However, tetradifon promoted a significant increase in the percentage of atretic follicles in the 12-weeks treated rats. Number and the diameter of mature follicles (tertiary and preovulatory) were markedly diminished together with a reduction of the relative weight of ovaries. Compared with controls, the treated rats exhibited significant reduction in serum 17beta-estradiol and progesterone levels. These results suggest an endocrine disruption by tetradifon which may interfere with ovarian follicles development in rat.

Oral repeat dose and reproductive toxicity of the chlorinated flame retardant Dechlorane Plus.

This study consisted of a 28-day oral repeat dose (repeat dose toxicity [RDT]) phase and a developmental and reproductive (developmental and reproductive toxicity [DART]) phase with rats. Rats were treated with Dechlorane Plus at doses of 0, 750, 1500, or 5000 mg/kg by gavage. For the RDT phase, no effects were observed on in-life parameters or clinical or anatomic pathology. In the DART phase, no effects were observed on reproductive or fertility indices, or fetal development through lactation day (LD) 4. No effects were noted on gestation day (GD) 20 implantation data, fetal indices, or external and visceral examinations. Mortalities occurred across all dose groups, although these were gavage-related errors and not compound related. Microscopic evidence of gavage-related errors included adhesions, inflammation, and fibrosis in the thoracic and pleural cavities. These findings were not test article related as they were observed only in animals with evidence of gavage injury. The no-observable-effect level (NOEL) in both phases of study was 5000 mg/kg.

Synthesis of a novel polymer bile salts-(polyethylene glycol)2000-bile salts and its application to the liver-selective targeting of liposomal DDB.

PURPOSE: The objective of this study was to achieve a sustained and targeted delivery of liposome to the liver, by modifying the phospholipid [phosphatidylcholine (PC)/cholesterol (10 : 1) liposomes with a novel polymer bile salts-(polyethylene glycol)(2000)-bile salts (BP(2)B). METHODS: First, we generated a novel BP(2)B by N,N'-dicyclohexylcarbodiimide/4-dimethylaminopyridine esterification method and confirmed by Fourier transform infraredand (1) H-NMR spectra. Second, we prepared the BP(2)B-modified liposomes (BP(2)BL) that included BP(2)B, and the effect of the weight ratios of BP(2)B/PC on entrapment efficiency was investigated and BP(2)B/PC = 3% (w/w) was determined as the optimum ratio for the 4,4'-dimethoxy-5,6,5',6'-bi (methylenedioxy)-2,2'-bicarbomethoxybiphenyl liposomes. And then, the ability of the liver target of BP(2)BL was studied by calculating the targeted parameters. RESULTS AND DISCUSSION: All the results revealed that the introduction of polyoxyethylene chains could control interactions of bile salt moieties on liposome surfaces with the receptor compared with traditional liposomes (CL), marking BP(2)BL as a suitable carrier for hepatic parenchymal cell-specific and sustained targeting. It was suggested that liposomes containing such novel BP(2)B have great potential as drug delivery carriers for the liver-selective targeting that has targeted and sustained drug delivery.

Dialkylcarbamoyl chloride-coated versus alginate dressings after pilonidal sinus excision: a randomized clinical trial (SORKYSA study).

BACKGROUND: Disease of the pilonidal sinus is a common condition that affects mainly young adults. Options for management include excision of the sinus tracts, leaving the wound open to heal by secondary intention. The aim of this study was to compare wound healing with dialkylcarbamoyl chloride (DACC)-coated dressings versus alginate dressings. METHODS: This multicentre trial randomized consecutive patients undergoing surgery for pilonidal disease to postoperative wound care with either DACC-coated or alginate dressings. The primary outcome was the proportion of wounds healed after 75 days. Secondary outcomes were the local status of wounds during the healing process, the quality assessment of the dressings by the patient, and the time needed to return to usual activities. RESULTS: A total of 246 patients were included: 120 in the DACC-coated group and 126 in the alginate group. In per-protocol analysis, there were significantly more patients with completely healed wounds after 75 days in the DACC group than in the alginate group: 78 of 103 (75·7 per cent) versus 58 of 97 (60 per cent) respectively (odds ratio 2·55, 95 per cent c.i. 1·12 to 5·92; P = 0·023). During follow-up, wounds with alginate dressings had more fibrin than those with DACC-coated dressings, but the difference was not significant (P = 0·079). There was no difference between the two arms in patients' assessment of the dressings. CONCLUSION: The number of wounds completely healed at 75 days was significantly higher for DACC-coated compared with alginate dressings. However, the preplanned, clinically significant improvement in healing of 20 per cent was not reached. Registration number: NCT02011802 ( https://clinicaltrials.gov/).

ANTECEDENTES: El sinus pilonidal es una afección común que afecta principalmente a adultos jóvenes. Las opciones de tratamiento incluyen la escisión de los trayectos del sinus, dejando la herida abierta para cicatrizar por segunda intención. El objetivo de este estudio fue comparar la cicatrización de heridas con apósitos recubiertos con cloruro de diaquilcarbamoilo (dialkylcarbamoyl chloride, DACC) en comparación con apósitos de alginato. MÉTODOS: En este ensayo multicéntrico se asignó al azar a pacientes consecutivos sometidos a cirugía por sinus pilonidal a uno de los dos brazos: cuidado postoperatorio de heridas con apósitos recubiertos con DACC o con alginato. El criterio de valoración principal fue la proporción de heridas curadas después de 75 días. Los criterios de valoración secundarios fueron el estado local de las heridas durante el proceso de curación, la evaluación de la calidad de los apósitos por parte del paciente y el tiempo necesario para volver a la actividad profesional. RESULTADOS: Se incluyeron un total de 246 pacientes: 120 en el grupo de apósitos recubiertos de DACC y 126 en el grupo de alginato. En el análisis por protocolo, hubo significativamente más pacientes con heridas completamente curadas después de 75 días en el grupo DACC que en el grupo de alginato: 78 de 103 (75,7%) y 58 de 97 (59,7%) respectivamente (razón de oportunidades, odds ratio, OR = 2,55; (1,12; 5,92); P = 0,02)). Durante el seguimiento, las heridas recubiertas con apósitos de alginato tenían más fibrina que las recubiertos con DACC, pero la diferencia no fue significativa (P = 0,08). No hubo diferencias entre los dos brazos en la evaluación realizada por los pacientes de los apósitos. CONCLUSIÓN: El número de heridas completamente curadas a los 75 días fue significativamente mayor con los apósitos recubiertos con DACC en comparación con los apósitos de alginato. Sin embargo, no se alcanzó la mejoría clínicamente significativa preestablecida de una curación del 20%.

Modulation of brain cation-Cl- cotransport via the SPAK kinase inhibitor ZT-1a.

The SLC12A cation-Cl- cotransporters (CCC), including NKCC1 and the KCCs, are important determinants of brain ionic homeostasis. SPAK kinase (STK39) is the CCC master regulator, which stimulates NKCC1 ionic influx and inhibits KCC-mediated efflux via phosphorylation at conserved, shared motifs. Upregulation of SPAK-dependent CCC phosphorylation has been implicated in several neurological diseases. Using a scaffold-hybrid strategy, we develop a novel potent and selective SPAK inhibitor, 5-chloro-N-(5-chloro-4-((4-chlorophenyl)(cyano)methyl)-2-methylphenyl)-2-hydroxybenzamide ("ZT-1a"). ZT-1a inhibits NKCC1 and stimulates KCCs by decreasing their SPAK-dependent phosphorylation. Intracerebroventricular delivery of ZT-1a decreases inflammation-induced CCC phosphorylation in the choroid plexus and reduces cerebrospinal fluid (CSF) hypersecretion in a model of post-hemorrhagic hydrocephalus. Systemically administered ZT-1a reduces ischemia-induced CCC phosphorylation, attenuates cerebral edema, protects against brain damage, and improves outcomes in a model of stroke. These results suggest ZT-1a or related compounds may be effective CCC modulators with therapeutic potential for brain disorders associated with impaired ionic homeostasis.

Subacute toxicity of polychlorinated naphthalenes and their effect on cytochrome P-450.

The aim of the study was to investigate the subacute toxicity of a polychlorinated naphthalene (PCN) mixture and its effect on cytochrome P-450 levels in rats. The animals were administered PCNs intragastrically in repeated daily doses of 1, 10, and 100 mg/kg. The animals were dissected after 7, 14, or 21 doses. Doses of 10 and 100 mg/kg induced a significant decrease in the body weight at all time points of the experiment compared with the control group. The exposure to PCNs increased both the level of total cytochrome P-450 and the activity of CYP 1A at the same time points. In the groups of rats given PCNs in doses of 10 and 100 mg/kg, an evident dose- and time-dependent increase in malondialdehyde (MDA) level was observed throughout the experiment. The correlation between the increased MDA and decreased glutathione (GSH) levels in the liver was also observed.

Glucuronidation and sulfonation, in vitro, of the major endocrine-active metabolites of methoxychlor in the channel catfish, Ictalurus punctatus, and induction following treatment with 3-methylcholanthrene.

The organochlorine pesticide, methoxychlor (MXC), is metabolized in animals to phenolic mono- and bis-demethylated metabolites (OH-MXC and HPTE, respectively) that interact with estrogen receptors and may be endocrine disruptors. The phase II detoxication of these compounds will influence the duration of action of the estrogenic metabolites, but has not been investigated extensively. In this study, the glucuronidation and sulfonation of OH-MXC and HPTE were investigated in subcellular fractions of liver and intestine from untreated, MXC-treated and 3-methylcholanthrene (3-MC)-treated channel catfish, Ictalurus punctatus. MXC-treated fish were given i.p. injections of 2mg MXC/kg daily for 6 days and sacrificed 24h after the last dose. The 3-MC treatment was a single 10mg/kg i.p. dose 5 days prior to sacrifice. In hepatic microsomes from control fish, the V(max) value (mean+/-S.D., n=4) for glucuronidation of OH-MXC was 270+/-50pmol/min/mg protein, higher than found for HPTE (110+/-20pmol/min/mg protein). For each substrate, the V(max) values observed in intestinal microsomes were approximately twice those found in the liver. The K(m) values for OH-MXC and HPTE glucuronidation in control liver were not significantly different and were 0.32+/-0.04mM for OH-MXC and 0.26+/-0.06mM for HPTE. The K(m) for the co-substrate, UDPGA, was higher in liver (0.28+/-0.09mM) than intestine (0.04+/-0.02mM). Treatment with 3-MC but not MXC increased the V(max) for glucuronidation in liver and intestine. Glucuronidation was a more efficient pathway than sulfonation for both substrates, in both tissues. The V(max) values for sulfonation of OH-MXC and HPTE, respectively, in liver cytosol were 7+/-3 and 17+/-4pmol/min/mg protein and in intestinal cytosol were 13+/-3 and 30+/-5pmol/min/mg protein. Treatment with 3-MC but not MXC increased rates of sulfonation of OH-MXC and HPTE and the model substrate, 3-hydroxy-benzo(a)pyrene in both intestine and liver. Comparison of the kinetics of the conjugation pathways with those published for the demethylation of MXC showed that formation of the endocrine-active metabolites was more efficient than either conjugation pathway. Residues of OH-MXC and HPTE were detected in extracts of liver microsomes from MXC-treated fish. This work showed that although OH-MXC and HPTE could be eliminated by glucuronidation and sulfonation, the phase II pathways were less efficient than the phase I pathway leading to formation of these endocrine-active metabolites.

Relationships among aural abscesses, organochlorine compounds, and vitamin a in free-ranging eastern box turtles (Terrapene carolina carolina).

Aural abscesses are a common health problem in free-ranging eastern box turtles (Terrapene carolina carolina), and they have been associated with high body burdens of organochlorine (OC) compounds, which are known disruptors of vitamin A. The objective of this study was to determine if the presence of pathologic lesions in box turtles were correlated with increased and decreased levels of hepatic OC compounds and vitamin A, respectively. A graded scale for the pathologic changes observed in tissue samples collected from abscessed and nonabscessed box turtles over a 2-yr period (2003-04) was developed, and the levels of OC compounds and vitamin A in livers collected from the same turtles were determined through chemical analysis. Sixty-eight turtles (40 with aural abscesses and 28 without) were included in the study. Relationships between variables were analyzed using Spearman's Rank Correlation Test, where P

Studies on the effect of chlorinated hydrocarbons content in the compound animal feeding stuffs on the residues in turkey carcasses and efficiency of slaughter turkeys rearing.

An increasing demand for turkey meat requires intensification of rearing, while almost permanent presence of stable chlorinated hydrocarbons in the environment, feeds, living organisms, including humans, to force undertaking studies on the wholesome safety of food of animal origin. The objective of the present study was therefore to evaluate selected cereals of different origin in terms of the content of chlorinated hydrocarbons (DDT, DDE, DDD, and HCH) as well as to determine the content of these compounds in turkey carcasses and their effect as feed material on the rearing efficiency. The investigations were carried out in 2002 on 100 one-day-old Big-6 turkey hens randomly allocated to 4 groups. For the period of 16 weeks, the animals were fed ad libitum with diets based on wheat and barley originating from different regions and characterized by different agricultural and industrial properties. Chlorinated hydrocarbons were determined in: animal feeding stuffs compound (wheat, barley, meat meal, extracted soybean meal), turkey blood, breast muscles, skin with external fat, and in abdominal fat by means of gas chromatography with an electron capture detector (ECD). The results obtained confirmed high contents of the examined compounds in feed material and in fat obtained from carcasses of the birds investigated.

Induction of microglial reactive oxygen species production by the organochlorinated pesticide dieldrin.

Exposure to pesticides has been speculated to contribute to the development of sporadic Parkinson's disease (PD) characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway. Activation of brain microglia that produce various neurotoxic factors including cytokines and reactive oxygen species (ROS) has been increasingly associated with dopaminergic neurodegeneration induced by various toxicants. Dieldrin, a highly persistent organochlorinated pesticide found enriched in the substantia nigra of some postmortem PD brains, has been shown to be toxic to dopamine neurons. In this study, we set out to determine the effect of dieldrin on the production of ROS and the underlying mechanism of action in murine microglia. Treatment of microglial cells with 0.1 nM to 1 microM dieldrin for 24 h resulted in a concentration-dependent generation of ROS. The dieldrin-induced microglial ROS generation was time-dependent in that significant ROS production was observed in cells 12-24 h, but not 6 h after dieldrin treatment. Furthermore, the dieldrin-induced microglial ROS generation was significantly reduced by inhibitors of NADPH oxidase, gene transcription and protein synthesis. In addition to immortalized microglial cells, dieldrin induced a concentration-dependent ROS generation in primary microglia, but not in primary astroglia. These results demonstrate that nanomolar concentrations of dieldrin can stimulate microglia to produce ROS that may contribute to the degeneration of dopamine neurons known to be vulnerable to oxidative damage. These findings provide important information on the potential role of microglia in dieldrin-induced neurodegeneration in relevance to the development of idiopathic PD.

Effect of drip application of ammonium thiosulfate on fumigant degradation in soil columns.

Low permeability tarps can effectively minimize fumigant emissions while improving fumigation efficacy by retaining fumigants under the tarp. However, when planting holes are cut through the tarps, high-concentration fumigants may be released and result in environmental and worker safety hazards. In a 11-day column study, we explored the effect of drip irrigation application of ammonium thiosulfate (ATS) on 1,3-dichloropropene (1,3-D) and chloropicrin (CP) degradation in soil. Decrease of 1,3-D and CP concentrations in soil-gas phase followed a three-parameter logistic equation for all treatments. It was slowest in the control with a half-life ( t 1/2) of 86.0 h for 1,3-D and of 16.3 h for CP and most rapid when ATS was applied at 4:1 ATS/fumigant molar ratio with a half-life of 9.5 h for 1,3-D and of 5.5 h for CP. Our results indicate that applying ATS via the drip-irrigation systems to soil can accelerate fumigant degradation in soil and thus reduce emissions. This technical solution may be applicable in raised-bed strawberry production where drip-application of fumigants under tarps has become common.

Dose verification after topical treatment of alligator (Alligator mississippiensis) eggs.

Numerous studies have used temperature-dependent sex determination in reptilian eggs to investigate potential developmental effects of exogenously applied substances. However, few studies have measured the dose carried across the eggshell. We report embryonic mortality and internal egg concentrations determined by gas chromatography-mass spectrometry two weeks after exposure of American alligator (Alligator mississippiensis) eggs to chlorinated organic pesticides via injection or topical application. Puncturing the eggshell for injection produced high mortality compared with unpunctured controls; therefore, further evaluation of this method was abandoned. Although higher than controls, mortality was much lower in eggs treated topically than in those injected. Transfer of chemicals across the eggshell was very low, highly variable, and did not correlate with the applied dose after topical application. These results are consistent with previous reports in the literature, casting doubt on whether a reproducible internal dose can be achieved in reptilian eggs by topical treatment.

Cancer mortality in workers exposed to organochlorine compounds in the pulp and paper industry: an international collaborative study.

The objective of this study was to evaluate cancer mortality in pulp and paper industry workers exposed to chlorinated organic compounds. We assembled a multinational cohort of workers employed between 1920 and 1996 in 11 countries. Exposure to both volatile and nonvolatile organochlorine compounds was estimated at the department level using an exposure matrix. We conducted a standardized mortality ratio (SMR) analysis based on age and calendar-period-specific national mortality rates and a Poisson regression analysis. The study population consisted of 60,468 workers. Workers exposed to volatile organochlorines experienced a deficit of all-cause [SMR = 0.91; 95% confidence interval (CI), 0.89-0.93] and all-cancer (SMR = 0.93; 95% CI, 0.89-0.97) mortality, with no evidence of increased risks for any cancer of a priori interest. There was a weak, but statistically significant, trend of increasing risk of all-cancer mortality with increasing weighted cumulative exposure. A similar deficit in all-cause (SMR = 0.94; 95% CI, 0.91-0.96) and all-cancer (SMR = 0.94; 95% CI, 0.89-1.00) mortality was observed in those exposed to nonvolatile organochlorines. No excess risk was observed in cancers of a priori interest, although mortality from Hodgkin disease was elevated (SMR = 1.76; 95% CI, 1.02-2.82) . In this study we found little evidence that exposure to organochlorines at the levels experienced in the pulp and paper industry is associated with an increased risk of cancer, apart from a weak but significant association between all-cancer mortality and weighted cumulative volatile organochlorine exposure.

The fate of chiral organochlorine compounds and selected metabolites in intraperitoneally exposed arctic char (Salvelinus alpinus).

The fate of chiral organochlorine compounds (OCs) and selected metabolites in exposed Arctic char (Salvelinus alpinus) was investigated. The contaminants alpha-hexachlorocyclohexane (alpha-HCH), cis-chlordane, 13C4-heptachlor, o,p'-DDT, and the atropisomeric chlorinated biphenyls (CBs) 95, 132, 136, 149, and 174 were solved in peanut oil and injected into the peritoneal cavity. The exposed fish were sampled three times during a five-week period, and the OC residues and detected metabolites (heptachlorexo-epoxide) were quantified in muscle and liver tissues by chiral and achiral gas chromatography-mass spectrometry and gas chromatography-electron-capture detection. Peak concentrations were reached after one to two weeks, and thereafter, the levels declined. At the end of the experiment, liver concentrations had decreased 76 to 92% relative to peak concentrations, whereas muscle concentrations showed a moderate decline (5-38%), with the exception of alpha-HCH (91%). Hydrophobicity and steric hindrance were shown to influence the assimilation process, and a significant linear relationship between the product of the steric hindrance coefficients and the inverse of the octanol-water partition coefficients (Kow) versus peak concentration was found for the CBs (r2 = 0.86, p = 0.02). The assimilation of the contaminants into muscle and liver tissues generally resulted in racemic mixtures, whereas elimination was enantioselective for alpha-HCH, cis-chlordane, o,p'-DDT, CB-132, and CB-136. The chiral heptachlor metabolite 13C4-heptachlor-exo-epoxide was formed in the fish. The enantiomeric composition of the formed metabolite indicated racemic formation, whereas the elimination process appeared to be enantioselective.

Effect of trichloropropene oxide on the ability of polyaromatic hydrocarbons and their "K-region" oxides to initiate skin tumors in mice and to bind to DNA in vitro.

The potent epoxide hydrase inhibitor, 1,1,1-trichloro-2,3-propene oxide (TCPO), enhanced the tumor-initiating ability of benzo[alpha]pyrene (BP) and 3-methylcholanthrene (MCA) but had no effect on 9,10-dimethyl-1,2-anthracene (DMBA) initiation in a two-stage system of tumorigenesis in female Charles River CD-1 mice. The tumor-initiating ability of dibenz[alpha,h]-anthracene (DBA) was decreased by prior topical treatment with 10 mumoles of TCPO. The tumor latency period of BP and MCA was decreased by TCPO but had no effect on DMBA or DBA. Topical treatment with 10 mumoles of TCPO did not initiate tumors in a two-stage system in mouse skin nor did it cause any histopathologic changes in the skin. The "K-region" epoxides of BP, DMBA, and MCA were weak tumor initiators when compared to the parent compounds. TCPO only slightly increased or had no effect on the tumor-initiating activity of the above epoxides. Pretreatment with Croton oil 18 hours prior to initiation with BP-4,5-epoxide also slightly enhanced the tumorigenic response in mouse skin. DBA-5,6-epoxide, when tested as a complete carcinogen at high doses (1 mg daily/10 days), was found to be a weak carcinogen but with activity comparable to that of DBA. TCPO only slightly increased the in vitro epidermally mediated covalent binding of the above parent polycyclic hydrocarbons to DNA.

Persistent organochlorine pollutants in children working at a waste-disposal site and in young females with high fish consumption in Managua, Nicaragua.

The aim of this study was to assess persistent organochlorine pollutant (POP) levels in serum collected from children (11-15 years old) working and sometimes also living at the municipal waste-disposal site in Managua, located at the shore of Lake Managua, and in nonworking children living both nearby and also far away from the waste-disposal site. The influence of fish consumption was further evaluated by assessing POPs levels in serum from young women (15-24 years old) with markedly different patterns of fish consumption from Lake Managua. 2,2-bis(4-chlorophenyl)-1,1,1-trichloro-ethane (4,4'-DDT) and 2,2-bis(4-chlorophenyl)-1,1-dichloro-ethene (4,4'-DDE), gamma-hexachlorocyclohexane (gamma-HCH), polychlorinated biphenyls, pentachlorophenol, and polychlorobiphenylols were quantified in all samples. In general, the levels observed were higher than those reported in children from developed countries, such as Germany and United States. Toxaphene, aldrin, dieldrin, and beta-HCH could not be identified in any sample. The children working at the waste-disposal site had higher levels of POPs compared with the nonworking reference groups. In children not working, there were also gradients for several POPs, according to vicinity to the waste-disposal site. Moreover, in children, as well as in young women, there were gradients according to fish consumption. The most abundant component was 4,4'-DDE, but at levels still lower than those reported in children from malarious areas with a history of recent or current application of 4,4'-DDT for vector control.