Relationship between inhibition of erythrocyte pyrimidine 5′-nucleotidase activity and biological response for porphyrin metabolism in workers occupationally exposed to lead

Summary A rapid determination of erythrocyte pyrimidine 5-nucleotidase (P5N) activity in lead workers was carried out using a high-performance liquid chromatograph (HPLC). The P5N activity had a good negative correlation with the concentration of lead in blood (PbB) ranging from 16 to 96 g/dl (r = -0.82, n = 77). Further, the P5N was compared with other biological parameters: erythrocyte -aminolevulinic acid dehydratase (ALAD) activity, erythrocyte protoporphyrin (PROTO), urinary -aminolevulinic acid (ALA) and urinary coproporphyrin (COPRO).The correlation coefficients between P5N and ALAD, log PROTO, log ALA, and log COPRO were 0.59, –0.72, –0.65, and –0.61, respectively. On the other hand, the normal value of P5N obtained from 72 healthy subjects was 11.9 ± 2.1 units; ol uridine/h/g Hb (mean ± SD), indicating that the lower limit of 95% confidence interval for normal P5N was about 8 units. When P5N was cut off at 8 units in 77 lead workers, the validity (sensitivity + specificity) for PbB 40 g/dl, PbB 60 gg/dl, erythrocyte PROTO 150 g/dl RBC, urinary ALA 6 mg/l, and urinary COPRO 150 g/l was 1.66, 1.76, 1.57, 1.68, and 1.60, respectively. From these results, it was confirmed that the erythrocyte P5N test is suitable for the biological monitoring of exposure to lead in a wide range, and its activity is useful in predicting the disturbance of porphyrin metabolism induced by lead.     

Erythrocyte pyrimidine 5′-nucleotidase activity in workers exposed to lead,mercury or cadmium

Summary The erythrocyte pyrimidine 5-nucleotidase activity (P5N) was measured in workers exposed to lead, cadmium or inorganic mercury and the effect of lead on this enzyme activity was compared with that on the classical biological parameters (ALAD, ZPP, ALAU), reflecting the interference of this metal with the heme biosynthesis pathway. P5N is inhibited by lead but not by cadmium and mercury. The correlation coefficient between log P5N and lead in blood (PbB) amount to 0.79 (n = 278; PbB ranging from 4.9 to 73.5 g/100 ml). The response of P5N to lead closely parallels that of ALAD.     

Response of free erythrocyte porphyrin and urinary δ -aminolevulinic acid in men and women moderately exposed to lead

Summary The responses of various biological parameters of the haem biosynthesis pathway in a group of adult male and female workers moderately exposed to inorganic lead have been compared. The identical range of blood lead levels in both groups indicates a similar degree of exposure. Women, however, exhibit a larger increase in free erythrocyte porphyrin (FEP) and in urinary -aminolevulinic acid (ALA-U) than men.The earlier response in women is probably not due to a relative degree of anaemia (menstrual blood loss) as compared to men, since there is no significant correlation between haemoglobin (Hb) and FEP or ALA-U, and consequently standardization for the same Hb-content does not modify the independent effect of lead on the FEP and ALA-U responses. A greater susceptibility to Pb of the haem biosynthesis pathway in women has therefore been confirmed by the results of the present epidemiological survey among workers of both sexes.A preliminary and limited survey on children (11 to 12 years old) of schools situated at less than 1 km from a Pb-processing plant revealed increased FEP and blood lead concentrations and demonstrated that like women children exhibit an earlier biological response to Pb-B than adult men.     

Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

Objective: The objective of the study was to validate a new and simple method to determine MOCA in the urine of exposed workers. Methods: The separation, identification and quantification of urinary MOCA were performed in spiked urines by a sensitive and practical high-performance liquid chromatography (HPLC) method and applied to urine samples of 11 workers occupationally exposed to MOCA; the postshift urinary levels of MOCA in their urine samples with and without hydrolysis, “total” and “free” MOCA respectively, were determined. In addition, we investigated the use of citric or sulfamic acid as preservatives of urine samples. Results: The “total” and “free” MOCA were extracted with isooctane from hydrolysed and nonhydrolysed 20-ml urine samples respectively. After evaporation, the residue was dissolved in 4 ml of 2 · 10⁻² M aqueous hydrochloric acid and analysed by an isocratic HPLC system using both ultraviolet (UV) detection at 244 nm and electrochemical detection working in oxidation mode (0.9 V) with an Ag/AgCl reference electrode. Mobile phase (50% acetonitrile in water containing 0.4% acetate buffer solution pH = 4.6) was used to complete the 20-min analysis. “Free” and “total” MOCA were chromatographed on a reversed-phase C8 column (5 μm; 250 mm × 4 mm). The standard curve of MOCA was linear over the range 5–500 μg/l in human urine. The detection limit was 1 μg/l for a 20-μl injection volume; the repeatability ranged from 5.6 to 1.3% (n = 6) for spiked urines at 5 and 500 μg/l, with a percentage recovery of 94 ± 3%. The reproducibility of the method was 7.3% (n = 4) for spiked urine at 10 μg/l. The use of sulfamic acid as a preservative of urine samples is important to improve the precision and accuracy of the analysis. Conclusion: The results indicate that these analytical procedures using conventional apparatus may be used routinely and reliably with large numbers of urine samples for biological monitoring of the exposure to MOCA. The occupational exposure to MOCA in some factories in France is studied in the second part of this work. Received: 10 November 1998 / Accepted: 25 March 1999     

Biological monitoring of workers exposed to 4,4′-methylene-bis-(2-orthochloroaniline) (MOCA)

OBJECTIVES: The objectives of the study were to investigate the best urinary marker of exposure to MOCA in urine samples of exposed workers and to study its applicability in exposure evaluation in polyurethane resin production plants. In addition, our intention was to contribute to the question of biological target value in order to reduce exposure levels. METHODS: Urinary MOCA markers were measured in urine samples collected at the end of the workshifts. 40 workers from four factories were observed for three consecutive days in the same week. "Free" MOCA in non-acid-stabilized urines, "total" MOCA in urines after alkaline hydrolysis, "acid-labile" MOCA in sulfamic or citric acid-protected urines were measured in all urine samples. MOCA liberated by heating the non-acid-stabilized urines ("heat-labile" MOCA) was also measured in 17 urine samples of exposed workers. RESULTS: The median value of "free" MOCA was lower than that of "sulfamic acid-labile" MOCA: 6.0 and 12.5 micrograms/l respectively. The difference between "free" and "total" MOCA was statistically significant (Mann-Whitney test, P = 0.023) for the urine samples collected without acid. Correlations between urinary MOCA concentrations in hydrolysed and non-hydrolysed urine samples were high (r = 0.984, 0.966 and 0.950; P < 0.001) for urine samples with sulfamic acid, with citric acid and without acid respectively. For all the factories, the postshift urinary MOCA concentrations ranged between 1 microgram/l (detection limit) and 570 micrograms/l; 25% of "sulfamic acid-labile" MOCA concentrations exceeded 50 micrograms/l. Workers handling crystallized MOCA excreted the highest amounts of MOCA in urine. The urinary MOCA concentrations (median) were: 84.0 micrograms/l (mixer), 15.5 micrograms/l (moulder). 59.0 micrograms/l (maintenance) and 3.0 micrograms/l (others). CONCLUSIONS: MOCA measured in sulfamic acid-protected urine samples without hydrolysis provides a more practical and reliable biomarker than "total" MOCA (after hydrolysis) or "free" MOCA. A biological guiding value of 20 micrograms/l expressed as "sulfamic acid-labile" MOCA is proposed.     

UrinaryN-acetyl-β-d-glucosaminidase and β-aminoisobutyric acid in workers occupationally exposed to metals such as chromium,nickel, and iron

Summary To examine the relationships between the urinary excretion ofN-acetyl--d-glucosaminidase (NAG) and -aminoisobutyric acid (AIBA) as a metabolite of thymine, and exposure to chromium, nickel, and iron, we determined these parameters in 58 workers engaged in the cutting and grinding of stainless steel or iron-steel plates. A significant increase in urinary NAG activity or urinary AIBA excretion was found in some of these workers. However, we could not find a significant positive correlation between the urinary excretion of NAG or AIBA and the urinary concentration of chromium, nickel, or iron as an indicator of internal dose.     

The effect of different warming methods on sensory nerve conduction velocity in shipyard workers occupationally exposed to hand–arm vibration

OBJECTIVES: Segmental sensory nerve conduction velocity (SNCV) was measured from the wrists to the hands and digits in a population of 134 (126 men and 8 women) vibration-exposed shipyard workers following systemic warming using a bicycle ergometer. Results were compared to earlier nerve conduction tests, identical in execution, except that the warming process was segmental and cutaneous. The study was designed to investigate whether SNCVs, which were selectively slow in the fingers after segmental cutaneous (skin surface) warming, would be affected differently by systemic warming. METHODS: Wrist-palm, palm-proximal digit, and digital sensory nerve segments were assessed antidromically by stimulating at the wrist with recording electrodes placed distally. The same subjects were cutaneously warmed in 2001 to >/=31 degrees C and were systemically warmed 28 months later in 2004 by ramped sustained exercise to 100 W for 12 min. Skin temperatures were measured by traditional thermistry and by infrared thermal images taken over the hand and wrist surfaces. RESULTS: When systemic warming was compared to segmental cutaneous warming, SNCVs were increased by 15.1% in the third digit and 20.4% in the fifth digit of the dominant hand. Respective increases in the non-dominant hand were 11.0% and 19.4%. A strong association between increased surface skin temperature and faster SNCV, which had been observed after segmental cutaneous warming, was largely eliminated for both digit and palmar anatomic segments after systemic warming. Significant differences in SNCV between vibration-exposed and non-exposed workers, which had been observed after segmental cutaneous warming, were eliminated after systemic warming. Systemic warming had only a small effect on the wrist-palm (transcarpal) segmental SNCVs. CONCLUSIONS: Reduced SNCV in the digits was observed in vibration-exposed and non-exposed workers. Substituting exercise-induced systemic warming for segmental cutaneous warming significantly increased SNCV in the digits and appeared to reduce differences in SNCV between vibration-exposed and non-exposed workers. These findings persisted despite a substantial time interval between tests, during which the subjects continued to work. There may be more general implications for diagnosing clinical conditions in industrial workers, such as the carpal tunnel syndrome and the hand-arm vibration syndrome.     

Biological monitoring of workers exposed to 4,4′-methylenediphenyl diisocyanate (MDI) in 19 French polyurethane industries

OBJECTIVES: To study the range of urinary levels of 4,4'-methylenedianiline (MDA), a metabolite of methylenediphenyl diisocyanate (MDI), across factories in the polyurethane industries and to evaluate the validity of this biomarker to assess MDI occupational exposure. METHODS: Workers exposed to MDI, as well as non-occupationally exposed subjects, were studied and pre- and post-shift urine samples were collected from 169 workers of 19 French factories and 120 controls. Details on work activities and practices were collected by a questionnaire and workers were classified into three job categories. The identification and quantification of the total urinary MDA were performed by high-performance liquid chromatography with electrochemical detection (HPLC/EC). RESULTS: For all the factories, MDA was detectable in 73% of the post-shift urine samples. These post-shift values, in the range of <0.10 (detection limit)-23.60 microg/l, were significantly higher than those of the pre-shift samples. Urinary MDA levels in the control group were in the range of < 0.10-0.80 microg/l. The degree of automation of the mixing operation (polyols and MDI) appears as a determinant in the extent of exposure levels. The highest amounts of MDA in urine were found in the spraying or hot processes. The excretion levels of the workers directly exposed to the hardener containing the MDI monomer were significantly higher than those of the other workers. In addition, skin exposure to MDI monomer or to polyurethane resin during the curing step were always associated with significant MDA levels in urine. CONCLUSIONS: Total MDA in post-shift urine samples is a reliable biomarker to assess occupational exposure to MDI in various industrial applications and to help factories to improve their manufacturing processes and working practices. A biological guiding value not exceeding 7 microg/l (5 microg/g creatinine) could be proposed in France.     

Improvement in the GC–MS method for determining urinary toluene-diamine and its application to the biological monitoring of workers exposed to toluene-diisocyanate

Objectives: To develop a simple and sensitive GC–MS method for determining toluene-diamine (TDA) in urine and to apply the method for biological monitoring of workers exposed to toluene-diisocyanate (TDI). Methods: After acid hydrolysis of 0.1 ml of urine, diluted tenfold with water, for 1.5 h, the free TDA formed was extracted with dichloromethane, and the heptafluorobutyric anhydride derivative was determined by GC–MS. We applied the method to the biological monitoring of 18 workers who were using an 80:20 mixture of 2,4-TDI and 2,6-TDI. Results: 2,6-TDA and 2,4-TDA were simply determined in 7 min by GC–MS. TDA levels in post-shift urine were well correlated with personal exposure levels of TDI. The correlation was improved by correction with creatinine or specific gravity in the 2,6-isomer, but not in the 2,4-isomer because of low exposure levels. From the correlation equation, the 2,6-TDA level (corrected with creatinine), corresponding to the TDI level of 5 ppb, was calculated to be 31.6 g/g Cre. TDAs in pre-shift urine also correlated significantly with the personal exposure levels of TDIs, although the slope of the correlations for pre-shift samples was 60%–70% of those for post-shift samples. The correlation between 2,4-TDA and 2,6-TDA levels was significant, although the levels of the 2,4-isomer were less than one-tenth of the 2,6-isomers in both air (personal exposure) and urine. Conclusion: The present method is simple and practicable and can be useful for biological monitoring of TDI workers.     

Exposure to traffic pollutants and effects on 17-β-estradiol (E2) in female workers

Objective: The aim of the study is to evaluate whether the occupational exposure to urban pollutants including endocrine disruptors (EDs) could cause alterations in plasma 17-β-estradiol (E2) levels and related diseases (adverse pregnancy outcome and mental health disorders) in female traffic police compared to a control group. Methods: After excluding the subjects with the principal confounding factors, traffic police and controls were matched by age, years of police work, age of menarche, menstrual cycle day, body mass index (BMI), drinking habit, cigarette smoking habit, habitual intake of soy or liquorice in diet and habitual consumption of Italian coffee. Thirty-seven traffic police and 31 controls (seventh day; follicular phase of the ovarian cycle); 38 traffic police and 42 controls (14th day; ovulatory phase of the ovarian cycle); and 25 traffic police and 28 controls (21st day; lutheal phase of the ovarian cycle) were included in the study and then matched for the above-mentioned variables. Results: In follicular and in lutheal phases, mean E2 levels were significantly lower in traffic police compared to controls. The distribution of E2 values in traffic police and controls was significant in follicular, ovulatory and lutheal phases. In ovulatory phase, mean E2 levels were lower but not significant in traffic police compared to controls. An increase was found concerning mental health disorders referred to in the questionnaire items in traffic police compared to controls, although the difference was not significant. Conclusions: Considering that the potential confounding effect of extraneous factors was controlled for by restricting the study population and by matching traffic police and controls on the above-mentioned variables, our results suggest that occupational exposure to urban pollutants, EDs included, might alter E2 plasma concentrations. E2 could be used in occupational set as an early biomarker of exposure to urban pollutants, valuable for the group, even before the onset of the related pathologies (adverse pregnancy outcome and mental health disorders).     

In Silico analysis of perturbed steroidogenesis and gonad growth in fathead minnows (P. promelas) exposed to 17α-ethynylestradiol

Abstract

The multi-factorial nature of adverse reproductive effects mediated by endocrine disrupting compounds (or EDCs) makes understanding the mechanistic basis of reproductive dysfunction a highly pertinent area of research. As a consequence, a main motivator for continued research is to integrate ‘multi-leveled’ complexity (i.e., from genes to phenotype) using mathematical methods capable of encapsulating properties of physiological relevance. In this study, an in silico stoichiometric model of piscine steroidogenesis was augmented with a ‘biomass’ reaction associating the underlying stoichiometry of steroidogenesis with a reaction representative of gonad growth. The ability of the in silico model to predict perturbed steroidogenesis and subsequent effects on gonad growth was tested by exposing reproductively active male and female fathead minnows (Pimephales promelas) to 88?ng/L of the synthetic estrogen, 17α-ethynylestradiol (EE2). The in silico model was parameterized (or constrained) with experimentally quantified concentrations of selected steroid hormones (using mass spectrometry) and fold changes in gene expression (using RT-qPCR) for selected steroidogenic enzyme genes, in gonads of male and female fish. Once constrained, the optimization framework of flux balance analysis (FBA) was used to calculate an optimal flux through the biomass reaction (analogous to gonad growth) and associated steroidogenic flux distributions required to generate biomass. FBA successfully predicted effects of EE2 exposure on fathead minnow gonad growth (%gonadosomatic index or %GSI) and perturbed production of steroid hormones. Specifically, FBA accurately predicted no effects of exposure on male %GSI and a significant reduction for female %GSI. Furthermore, in silico simulations accurately identified disrupted reaction fluxes catalyzing productions of androgens (in male fish) and progestogens (in female fish), an observation which agreed with in vivo experimentation. The analyses presented is the first-ever to successfully associate underlying flux properties of the steroidogenic network with gonad growth in fish, an approach which can incorporate in silico predictions with toxicological risk assessments.     

Prevalence of 5′ insertion mutants and analysis of single nucleotide polymorphism in the erythrocyte binding-like 1 (ebl-1) gene in Kenyan Plasmodium falciparum field isolates

Plasmodium merozoites attach to and invade red blood cells (RBCs) during the erythrocytic cycle. The invasion process requires recognition of RBC surface receptors by proteins of the Plasmodium Duffy binding like erythrocyte binding like (DBL-EBP) family. Clones and isolates of Plasmodium falciparum have varying abilities to utilize different RBC receptors, and multiple distinct pathways so far identified depend on glycophorins A, B, C, and as yet unidentified receptors. At present, five members of the DBL-EBP family have been identified in the P. falciparum genome, based on gene structure and amino acid sequence homology. The cardinal features of this family consist of conserved 5′ and 3′ cysteine-rich regions (regions II and VI, respectively) whose cysteine residues are highly conserved along with the majority of aromatic amino acids. In contrast to the single DBL-EBP family member in Plasmodium vivax, in P. falciparum all DBL-EBP family members have a duplication of the conserved 5′ cysteine-rich region denoted as the F1 and F2 domains. These cysteine-rich regions are considered crucial in recognition of erythrocyte receptors and it has been shown that several bind to glycophorins on the erythrocyte surface. Several studies, on both field isolates and laboratory strains have uncovered a relatively high degree of sequence polymorphism in the DBP-EBL genes. This study is now extended to include field isolates collected from sites within Kenya. DNA isolated from blood samples of infected patients was utilized to amplify the region I sequence of ebl-1 gene in order to investigate polymorphism in the region immediately adjacent to the 5′ cysteine-rich domains, and to determine the prevalence of an insertion mutant that effectively knocks out the gene.     

Immunodeficiency and lymphocyte ecto-5′-nucleotidase activity in the elderly: A comparison of the effect of a trace mineral supplement (1 USRDA) with high zinc (6.7 X USRDA)

The effect of administering a total mineral supplement (TMS) or 100 mg of elemental zinc alone on immune function was studies in 17 normal subjects, aged 66–85. Subjects were given either TMS containing 1 USRDA of zinc, copper, iron, and manganese or 100 mg of elemental zinc alone as zinc sulfate (ZnSO₄). Administration of either supplement led to a slight increase in peripheral blood lymphocytes and improved maturation of B-lymphocytes to antibody-producing cells in culture of peripherla blood mononuclear cells. Ecto-5′-nucleotidase, a zinc obligate enzyme of lymphocyte cell membranes, increased when TMS was administered daily but failed to increase when ZnSO₄ was administered. Serum zinc levels increased in all subjects receiving the ZnSO₄. Only those subjects with low initial serum zinc levels had higher serum zinc levels after 3 months on the TMS. These studies indicate that dietary supplementation with a TMS (1 USRDA) can improve certain in vitro parameters of immune competence in the aged, avoiding the deleterious effects possible with excessive intake.     

Mutagenicity of 4,4′-methylene-bis-(2-chloroaniline) “MOCA” and its N-acetyl derivatives in S. typhimurium

Summary 4,4-methylene-bis-(2-chloroaniline) (MOCA) and two identified urinary N-acetyl and N,N-diacetyl derivatives were tested in a Salmonella/mammalian microsome assay. No mutagenic activity was observed without rat liver S9 mix activation. In the presence of rat liver S9 mix, the chemicals were mutagens, but the mutagenicity of N-acetyl derivatives to strain TA 100 was reduced when compared to that of MOCA, and a greater amount of S9 was required to exhibit the mutagenicity of the N,N-diacetyl-MOCA. These data suggest that N-acetylation does not account for the mutagenic effectiveness of MOCA.     

Genetically highly divergent RNA virus with astrovirus-like (5′-end) and hepevirus-like (3′-end) genome organization in carnivorous birds,European roller (Coracias garrulus)

Astroviruses (family Astroviridae) and hepeviruses (family Hepeviridae) are small, non-enveloped viruses with genetically diverse +ssRNA genome thought to be enteric pathogens infecting vertebrates including humans. Recently, many novel astro- and hepatitis E virus-like +ssRNA viruses have been described from lower vertebrate species. The non-structural proteins of astro- and hepeviruses are highly diverse, but the structural/capsid proteins represent a common phylogenetic position shed the light of their common origin by inter-viral recombination. In this study, a novel astrovirus/hepevirus-like virus with +ssRNA genome (Er/SZAL5/HUN/2011, MK450332) was serendipitously identified and characterized from 3 (8.5%) out of 35 European roller (Coracias garrulus) faecal samples by RT-PCR in Hungary. The complete genome of Er/SZAL5/HUN/2011 (MK450332) is 8402 nt-long and potentially composed three non-overlapping open reading frames (ORFs): ORF1a (4449 nt/1482aa), ORF1b (1206 nt/401aa) and ORF2 (1491 nt/496aa). The ORF1ab has an astrovirus-like genome organization containing the non-structural conserved elements (TM, CC, NLS, VPg) and enzyme residues (trypsine-like protease, RNA-dependent RNA-polymerase) with low amino acid sequence identity, 15% (ORF1a) and 44% (ORF1b), to astroviruses. Supposedly the ORF2 is a capsid protein but neither the astrovirus-like subgenomic RNA promoter (sgRNA) nor the astrovirus-like capsid characteristics have been identifiable. However, the predicted capsid protein (ORF2) showed 26% identity to the corresponding protein of hepevirus-like novel Rana hepevirus (MH330682). This novel +ssRNA virus strain Er/SZAL5/HUN/2011 with astrovirus-like genome organization in the non-structural genome regions (ORF1a and ORF1b) and Rana hepevirus-related capsid (ORF2) protein represent a potentially recombinant virus species and supports the common origin hypothesis, although, the taxonomic position of the studied virus is still under discussion.     

Sociodemographic factors and trends on overweight prevalence in children and adolescents in Aragón (Spain) from 1985 to 1995

From 1985 to 1995, the Aragón School Health Examination Surveys staff has surveyed the whole population of children (age 6-7 years) and adolescents (age 13-14 years). A total of 90,997 children (age 6-7 years) were examined in the nine cross-sectional surveys conducted between 1985 and 1995. A total of 106,284 adolescents (age 13-14 years) were also examined. We defined overweight when the body mass index was > or = 95th percentile. The measure of association between overweight and the other variables studied was the odds ratio, which was calculated by logistic regression. In the children and adolescents studied, the probability to be overweight was higher in the rural than in the urban areas. In the adolescents, the probability to be overweight was higher in the public than in the private schools. Our results also show a significant increase in the prevalence of overweight children in the region of Aragón (Spain) during the 1985-1995 decade, especially in males. Prevention of overweight in the populations at risk would help reduce social inequality in health, a major challenge for public health policy.     

Acute toxicity,percutaneous absorption and effects on hepatic mixed function oxidase activities of 2,4,4′-trichloro-2′-hydroxydiphenyl ether (Irgasan® DP300) and its chlorinated derivatives

Acute toxicity of 2,4,4-trichloro-2-hydroxydiphenyl ether (Irgasan^® DP300) (I) and its three chlorinated derivatives, 2,3,4,4-tetrachloro-2-hydroxydiphenyl ether (II), 2,4,4,5-tetrachloro-2-hydroxydiphenyl ether (III) and 2,3,4,4,5-pentachloro-2-hydroxydiphenyl ether (IV), in mice were examined by intraperitoneal injection. The LD₅₀ values of Irgasan DP300, II, III and IV were 1,090, 710, 650 and 430 mg/kg, respectively.The percutaneous absorptions of these tritiated compounds were also examined by the application on the backs of mice. The radioactivities in most tissues reached to the maximal levels at 12 h or 18 h after dosing, which corresponded to 11–76% of the maximal levels given by the oral administration (Kanetoshi et al. 1988a). These results show the high percutaneous absorbability of Irgasan DP300 and its chlorinated derivatives.The intraperitoneal administrations of III and IV to rats induced hepatic microsomal aminopyrine N-demethylase and aniline 4-hydroxylase activities similarly to phenobarbital. These chlorinated derivatives also increased cytochrome P-450 content, and the activities of aminopyrine N-demethylase and N-methylaniline N-demethylase in hepatic microsomes from mice. The extents of the increases were similar to those by phenobarbital and 3-methylcholanthrene.     

Sperm Aneuploidy in Faroese Men with Lifetime Exposure to Dichlorodiphenyldichloroethylene (p,p′-DDE) and Polychlorinated Biphenyl (PCB) Pollutants

Background:

Although it is known that sperm aneuploidy contributes to early pregnancy losses and congenital abnormalities, the causes are unknown and environmental contaminants are suspected.

Objectives:

Our goal was to evaluate associations between lifetime exposure to organochlorines, specifically dichlorodiphenyldicholorethylene (p,p´-DDE) and polychlorinated biphenyls (PCBs), and sperm aneuploidy in men from the general population of the Faroe Islands, a population with a known history of organochlorine exposures.

Methods:

Serum and semen samples from men (n = 90) 22–44 years old who participated in Faroe Islands health studies were analyzed for p,p´-DDE and PCBs 118, 138, 153, and 180 and adjusted for total lipids. Cord blood and age-14 serum were available for a subgroup (n = 40) and were also analyzed for p,p´-DDE and PCBs. Sperm fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was used to determine rates of XX18, XY18, YY18, and total disomy. Multivariable adjusted Poisson models were used to estimate the relationship between organochlorine exposure and sperm disomy outcomes.

Results:

Adult p,p´-DDE and total PCB serum concentrations were both associated with significantly increased rates of XX18, XY18, and total disomy. Age-14 p,p´-DDE and PCB concentrations were both associated with significantly increased rates of XX, XY, and total disomy in adulthood. Associations between cord blood concentrations of p,p´-DDE and PCBs and sperm disomy in adulthood were not consistently significant.

Conclusions:

Organochlorine exposures measured at age 14 and in adulthood were associated with sperm disomy in this sample of high-exposure men, suggesting that the impacts of persistent pollutants on testicular maturation and function require further investigation.

Citation:

Perry MJ, Young HA, Grandjean P, Halling J, Petersen MS, Martenies SE, Karimi P, Weihe P. 2016. Sperm aneuploidy in Faroese men with lifetime exposure to dichlorodiphenyldichloroethylene (p,p´-DDE) and polychlorinated biphenyl (PCB) pollutants. Environ Health Perspect 124:951–956; http://dx.doi.org/10.1289/ehp.1509779     

Metabolism and storage ofp,p′ dicofol in American kestrels (Falco sparverius) with comparisons to Ring Neck Doves (Streptopelia risoria)

Residues ofp,p dicofol,p,p dichlorobenzophenone (p,p DCBP),p,p dichlorobenzhydrol (p,p DCBH), 1,1-bis (4-chlorophenyl)-2,2-dichloroethanol (p,p DCD) and 1,1-bis (4-chlorophenyl)-2,2 dichloroethylene (p,p DDE) are reported in liver, fat, brain and oviducts of American kestrels exposed top,p dicofol. Breeding female kestrels were exposed to oral gavage dosages of 3.0 and 0.3 mg dicofol/kg body weight per day, equivalent to 1 or 10 mg dicofol/kg diet, for 39 days. Kestrels exhibited an eggshell thinning response similar to that produced by DDE, under these exposures. The major hepatic metabolite of dicofol in kestrels was DCD, but most organochlorine stored in tissues was in the form of dicofol. DDE was not a major metabolite of dicofol in kestrels. Compared with doves, kestrels had a significantly reduced metabolic capacity to transform dicofol to DCBP and DCBH, and had a steeper dose-response curve for dicofol-induced eggshell thinning.