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Biomedical subjects

L G Hansen

Publications and source records attributed to L G Hansen.

At least 19 recordsLinked to original sources
PubMed1999

Short-term distribution, metabolism, and excretion of 2,2',5-tri-, 2, 2',4,4'-tetra-, and 3,3',4,4'-tetrachlorobiphenyls in prepubertal rats.

The excretion and tissue retention of three 14C-labeled lower chlorinated biphenyls were examined in prepubertal male and female Sprague-Dawley rats following IV administration. Urine and feces were collected individually at different time intervals up to 72 h for pharmacokinetic analyses. After 72 h, different organs were removed and extracted in acetone:hexane (1:1, v/v) to determine radioactivity. Within the first 10 h after dosing, 2,2', 5-trichlorobiphenyl (PCB 18) was rapidly excreted in urine (8-18% of the administered dose), whereas only 0.6-0.8% of 2,2',4, 4'-tetrachlorobiphenyl (PCB 47) and 0.3-0.8% 3,3',4, 4'-tetrachlorobiphenyl (PCB 77) were found in urine during this time period. The half-life of elimination was shortest for PCB 18 (37.5 to 49.2 h). The half-lives for PCB 47 and PCB 77 were 351 to 672 h and 152 to 186 h, respectively. The cumulative total excretion (urinary + fecal) of PCB 18 within 72 h was 51-62%, of PCB 77 was 22-25%, and of PCB 47 was 7-10%. No parent PCBs were detected in urine. PCB 47 accumulated preferentially in adipose tissues (subcutaneous fat > mesenteric fat); relatively high levels of PCB 47 were also found in adrenals, ovaries, lungs, liver, and skin. The highest concentration of PCB 77 was found in serum, followed by adipose tissues. Very low concentrations of PCB 18 were found in most tissues; the highest being found in serum, followed by ovaries and adrenal glands. This study suggests that prepubertal rats retain higher short-term serum levels and have lower excretion rates than adult rats.

Animals↗
PubMed1998

Hepatic enzyme induction and acute endocrine effects of 2,3,3',4',6-pentachlorobiphenyl in prepubertal female rats.

Polychlorinated biphenyls (PCBs) with the labile 2,3,6-substitution are important components of atmospheric and certain food chain exposures, but little is known about their biological activities. Chlorobiphenyl 110 (2,3,3',4',6-pentaCB) was investigated in weanling female rats dosed ip on days 21 and 22 and killed on day 23 of age. The initial preparation of CB 110 markedly induced 7-ethoxyresorufin O-dealkylase (EROD) activity and was found to be contaminated with coplanar 3,3',4,4',5-pentaCB (CB 126). The contaminated preparation (CB 110C) was purified with activated charcoal (CB 110P). The CB 110P induced pentoxyresorufin O-dealkylase (PROD), was weakly uterotropic and a modest depleter of serum thyroxine (T4). CB 110C caused increased liver weight, induced EROD, PROD, and UDP glucuronyl transferase activities and caused a greater depletion of serum T4; on the other hand, it suppressed the PROD induction and the uterotropic effect of CB 110P. Hepatic residues of CB 110 were a constant 2-3% of the dose while those of CB 126 (from CB 110C) increased with increasing dose to as much as 50% of the dose.

Animals↗
PubMed1998

Forms and prevalence of intersexuality and effects of environmental contaminants on sexuality in cricket frogs (Acris crepitans).

Cricket frogs (Acris crepitans) from several different sites in Illinois were collected to assess the effects of environmental contamination on the prevalence of intersex gonads. Of 341 frogs collected in 1993, 1994, and 1995, 2.7% were intersex individuals. There was no statistically significant relationship between the chemical compounds detected and cricket frog intersexuality. However, there was an association approaching significance (p = 0.07) between the detection of atrazine and intersex individuals. A comparison of reference sites with sites that had point polychlorinated biphenyl (PCB) and polychlorinated dibenzofuran (PCDF) contamination revealed a significant relationship between sex-ratio reversal and contamination with PCBs and PCDFs. The sex ratio of juvenile frogs studied from three sites with PCB and PCDF point contamination favored males over females, which was the opposite of the sex ratio in control ponds (p = 0.0007). The statistically significant correlation between organochlorine contamination and sex-ratio reversal suggests PCBs and PCDFs can influence cricket frog sexual differentiation. The current study suggests that in cricket frogs, sex ratios and the prevalence of intersex gonads are altered by environmental contamination.

Aging↗
PubMed1998

Stepping backward to improve assessment of PCB congener toxicities.

Polychlorinated biphenyls (PCBs) are ubiquitous global contaminants that have been intensively investigated for three decades. They are broad-acting toxicants occurring in complex mixtures and accurate risk assessment has proven to be elusive. Focusing on a limited set of end points and emphasizing a fixed set of congeners have led to more streamlined data sets that are meant to expedite hazard characterization and risk assessment for the most potent congeners--aryl hydrocarbon receptor (AhR) agonists. Unfortunately, this has made it impossible to confirm or deny significant contributions from the more prevalent components of the mixtures. PCBs may be only coincidentally present, rather than causal, in some diseases. Still, attempts to determine associations with incomplete residue data may lead to erroneous conclusions and make accurate risk assessment even more elusive. Responses not mediated through the AhR are presented and emphasize large data gaps. Dissimilar analytical reports emphasize that selection of analytes is not consistent. Collectively, these data confirm that AhR-focused objectives unintentionally created the impression that nonplanar PCBs have little if any potential for hazards to humans and wildlife. Near steady-state exposure of healthy adults are probably of minor consequence except for emerging correlations with non-Hodgkin's lymphoma; however, pulses of exposure to more labile mixtures may contribute to developmental effects without leaving a residue record. More broadly based criteria are suggested and harmonization of data collection and presentation are desirable. A more comprehensive list of PCB congeners is proposed that would provide more adequate data upon which to base associations with adverse outcomes.

Animals↗
PubMed1997

Morphometric changes in the prepubertal female rat thyroid gland following acute exposure to 2,2',4,4'-tetrachlorobiphenyl and Aroclor 1242.

Weanling female Sprague-Dawley rats were given either 2 or 5 consecutive daily doses of 30 mg/kg 2,2',4,4'-tetrachlorobiphenyl (CB 47) or a total dose of 120 mg/kg Aroclor 1242 divided into 2, 3, or 5 daily doses by intraperitoneal injection. One day after the final dose, serum total thyroxine (T4) was determined and thyroid glands were collected and prepared for morphometric analysis. Serum T4 increased between 20 and 25 d of age, but declined to 35-52% of controls by d 25 in PCB-treated rats. In rats receiving only 2 doses of CB 47, the declines in serum T4 were more modest but the thyroid follicular epithelial cell height increased from 9 microns to 10-12 microns and the colloid area decreased from 1100 microns2 to 800-900 microns2. In Aroclor 1242-treated rats, follicular cell height increases and colloid area decreases were somewhat greater; serum T4 was higher (partially restored) in the rats having received earlier doses. The rapid response of the thyroid gland to moderate decreases in serum T4 attenuates the observed decrease in T4 and may mask effects on T4 metabolism in short-term structure-activity studies. Morphometric measurements may be helpful in characterizing early and/or transient responses to toxicants such as PCBs that have multiple endocrine disrupting effects.

Animals↗
PubMed1996

Effects of 3-iodo-L-tyrosine, a tyrosine hydroxylase inhibitor, on eye pigmentation and biogenic amines in the planarian, Dugesia dorotocephala.

Planarians (Dugesia dorotocephala) were evaluated as bioassay organisms to detect inhibition of tyrosine hydroxylase, the rate-limiting enzyme in the synthesis of catecholamines. Thirty planaria per dose were exposed to 0 (control), 0.001, 0.01, 0.1, or 1 mM 3-iodo-L-tyrosine (monoiodotyrosine or MIT) in standard test media beginning 24 hr before decapitation and continuing for 13 days. Complete regeneration of normal heads occurred over the first 6 days in all dose groups, a response reported to be partially dependent on catecholamines. Beginning on Day 7, the black eye pigments began fading in the 0.1 and 1 mM dose groups and were completely absent macroscopically and histologically by Day 11. The 0, 0.001, and 0.01 mM dose groups did not lose visible eye pigments. On Day 13, 3 planaria/dose were harvested for histopathology; 15 planaria/dose were decapitated a second time and remained in MIT solutions; and 12 planaria/dose were left intact, placed in fresh control media, and evaluated for eye repigmentation. Normal head regeneration (including eyes) was detected grossly in all groups, even in those animals devoid of eye pigments at the time of decapitation. As before, eye pigments began fading 7 days after decapitation (Day 20 of experiment) and were completely absent in 73 and 33% of the animals in the 0.1 and 1 mM groups, respectively, on Day 25. All animals moved to control media reformed eye pigments, beginning within 48 hr. Analysis of the decapitated heads by HPLC-ECD on Day 13 revealed a significant decrease in dopamine and 5-hydroxytryptamine (serotonin) concentrations in MIT-exposed animals. Tyrosine hydroxylase activity (and possibly tyrosinase activity) was shown to be inhibited by the highest two concentrations for whole planaria homogenates in vitro.

Animals↗
PubMed1996

Responses of prepubertal female rats to environmental PCBs with high and low dioxin equivalencies.

An extract of landfill soil containing high levels of polychlorinated biphenyls (PCBs) was refined by alumina-charcoal column chromatography to remove coplanar PCBs and high relative levels of PCDFs. Both extracts were administered ip in corn oil to immature female rats on Days 21 and 22 of age. Rats were terminated on Day 23 and organ weights, enzyme activities, and serum thyroxine (T4) were measured. The change in characteristics caused by charcoal-stripping was confirmed by comparing hepatic microsomal 7-ethoxyresorufin O-deethylase (EROD), 7-pentoxyresorufin O-depentylase (PROD), 7-benzyloxyresorufin O-dearylase (BROD), and UDP glucuronyl transferase (UDPGT) activities. EROD and 4-nitrophenol (4-NP) UDPGT activities, estimates of aryl hydrocarbon (Ah) receptor agonists present, peaked at 140 mg/kg soil extract, declining at 210 mg/kg; these activities in rats treated with the charcoal-refined soil extract were not induced at low doses, but increased linearly from 70 to 210 mg/kg. Conversely, PROD and BROD activities were modestly induced at 7 to 70 mg/kg of either soil extract; however, at higher doses induction was threefold higher in rats receiving the charcoal-filtered extract. Liver weights increased in a pattern similar to EROD induction. At all doses, the weak uterotropic response was greater in rats receiving the charcoal-filtered extract, probably due to removal of antiestrogenic Ah receptor agonists by the charcoal. Serum total T4 declined similarly in rats receiving either extract to about 40% of control values at the highest doses. Short-term integrated bioassays such as this are useful in detecting multiple complex interactions and can be used to define the net effects of mixtures with changing compositions for improved risk assessment.

Animals↗
PubMed1996

Neonatal polychlorinated biphenyl treatment increases adult testis size and sperm production in the rat.

Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants which decrease serum thyroxine (T4) concentrations. We have previously demonstrated that neonatal hypothyroidism in the rat increases Sertoli cell numbers, adult testis weight, and daily sperm production (DSP). The aim of this study was to determine if neonatal PCB treatment increases adult testis weight and DSP. Treated rats received either Aroclor 1242 or 1254 (0.4-3.2 mg/day), from birth to Day 25 by daily injection; some treated litters also received T4 replacement. Controls received vehicle alone. Tritiated thymidine autoradiography was used to assess Sertoli cell proliferation in 15-day control and Aroclor-treated rats. Serum T4 was measured at 25, 45, and 135 days of age, and serum testosterone, testis weight, DSP, and testicular histology were examined at 135 days. Both Aroclor 1242 and 1254 suppressed serum T4 concentrations; Aroclor 1254 was more potent and long lasting. Testis weight was increased 22 and 13% in rats that received the 1.6 and 3.2 mg/day Aroclor 1242 doses, respectively, while the 0.4 mg/day dose did not produce significant increases. Aroclor 1254 produced significant increases in testis weight of 13 and 23% at the 0.4 and 1.6 mg/day doses, respectively. The 1.6 mg/day Aroclor 1242 and the 0.4 and 1.6 mg/day Aroclor 1254 doses increased DSP by 27, 11, and 42%, respectively; other treatments did not produce significant increases. At 15 days of age, Sertoli cell proliferation was greater in treated rats than in controls. T4 replacement decreased or eliminated the increased testis weight and DSP seen in Aroclor-treated rats. The highest dose of Aroclor 1242 and both doses of Aroclor 1254 decreased adult body weight, while other treatments did not. These results indicate that neonatal PCB treatment increases adult testis weight and DSP in rats. PCBs produce this effect primarily by inducing hypothyroidism, which leads to increased Sertoli cell proliferation, testis weight, and DSP. Thus PCBs, despite inhibitory effects on adult reproductive organs, can paradoxically stimulate increases in adult testis weight and DSP when administered neonatally. These data emphasize the pleiotropic nature of PCB effects and the susceptibility of the developing reproductive system to environmental factors.

Animals↗
PubMed1996

Polychlorinated dibenzofurans and dibenzo-p-dioxins in subsurface soil, superficial dust, and air extracts from a contaminated landfill.

Extracts of soil, dust and air from a National Priorities List Landfill have been found to contain distinct profiles of polychlorinated biphenyls (PCBs). The different extracts show subtle differences in toxicities and the soil extract has been shown to cause both Ah receptor mediated effects and Ah receptor independent effects in immature female rats. Evidence of open burning at the site dictated quantitation of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) for a more accurate tabulation of dioxin equivalencies. High volume air sampling on XAD-2 resin cartridges captured trace amounts of PCDFs and no detectable PCDDs. Acetone:Hexane (1:1) extracts of soil and dust contained 762 microg/ml and 250 microg/ml PCDFs, respectively, and less than 10% as much PCDD. Subsequent benzene:methylene chloride (1:1) extracts were enriched in coplanar compounds relative to total PCBs. PCDF:PCB ratios in all extracts were higher than in the rice oils contaminated with heated PCBs in the Yusho and Yu-Cheng incidents. No 2,3,7,8-TCDD was detected, and total PCB+PCDD+PCDF toxic equivalencies were dominated by the high proportions of PCDFs.

Air Pollutants↗
PubMed1996

Enzyme induction and acute endocrine effects in prepubertal female rats receiving environmental PCB/PCDF/PCDD mixtures.

Air, subsurface soil, and superficial dust from a National Priorities List landfill located in southern Illinois were sampled to determine their potential toxicities. The major components of these landfill extracts were polychlorinated biphenyls (PCBs), with significant amounts of polychlorinated dibenzofurans (PCDFs) and small amounts of polychlorinated dibenzodioxins (PCDDs). The 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) toxic equivalency factor approach has been proposed to estimate the toxic potency of complex mixtures of chlorinated aromatics for environmental risk assessment. However, most components of environmental residues are nonplanar and do not act as aryl hydrocarbon (Ah) receptor agonists, so there is a great risk of not identifying adverse responses that are not dioxinlike. We used a 2-day prepubertal female rat bioassay to examine multiple biological responses, including both dioxinlike and nondioxinlike effects from these landfill extracts. As expected, both types of effects were detected. The soil and dust extracts produced similar dose-response relationships for 7-ethoxyresorufin O-deethylase, 7-pentoxyresorufin O-depentylase, 7-benzyloxyresorufin O-debenzylase, and 4-nitrophenol UDP-glucuronyltransferase induction; the dose response for the air extract deviated from the other two extracts. Soil, dust, and air extracts effectively reduced serum total thyroxine (T4) with similar dose-response relationships, despite the significantly different TCDD toxic equivalent (TEQ) values of these three extracts. Both soil (346 mg PCB/kg) and air (175 mg PCB/kg) extracts caused a greater than 30% increase in uterine wet weight. This study suggests that a more comprehensive approach is required to improve current risk assessment of environmental mixtures. TCDD TEQs reflect only a portion of effects and may especially underpredict effects on T4.

Air Pollutants↗
PubMed1995

Toxicities of 2,2',4,4'- and 3,3',4,4-tetrachlorobiphenyls to house flies at different ages and enzyme levels.

Two tetrachlorobiphenyls (2,2',4,4'-tetraCB and 3,3',4,4'-tetraCB) had different effects on the longevity of adult female house flies (Musca domestica), depending on enzyme levels at dosing. Twenty-four-hour acute toxicities of the two tetrachlorobiphenyls were also compared with one trichlorobiphenyl (2,2',5-triCB) at different enzyme levels. 2,2',4,4'-tetraCB killed more than 90% of the flies within 12 h at the highest dose (1,667 ppm, micrograms/g); however, the toxicity of the moderate dose (1,250 ppm) was age-dependent and greater in 1- and 15-day-old flies and lower in 5-day-old flies. Daily mortality patterns of the lower doses (390 and 833 ppm) were similar to the control. LT50s (time for 50% death) were also different in different age groups at the moderate dose. The toxicity of 3,3',4,4'-tetraCB was similar to the control in all age groups, with a slight increase in the early mortalities and a decrease in the LT50s at the highest (1,200 ppm) dose. The twenty-four-hour lethality of 2,2',4,4'-tetraCB was very high, even at the lower doses in 1- and 15-day-old flies. Lower doses were least toxic at day 5, when the levels of cytochrome P450 enzymes were at the highest. On the other hand, the acute toxicity of 2,2',5-triCB increased from 5 and 15% in 1- and 15-day-old flies, respectively, to about 50% in 5-day-old flies, suggesting bioactivation of 2,2',5-triCB. The acute toxicity of 3,3',4,4'-tetraCB was negligible in all ages of house flies.

Abdomen↗
PubMed1995

Environmental polychlorinated biphenyls: acute toxicity of landfill soil extract to female prepubertal rats.

Subsurface soil from a National Priorities List landfill containing about 2.5% polychlorinated biphenyls (PCBs) was extracted and the extract cleaned by Florisil slurry and alumina column chromatography. The refined extract contained 48 mg/mL PCB, mainly trichlorobiphenyls and tetrachlorobiphenyls, traces of polychlorinated naphthalenes, 125 micrograms/mL 2,2-bis-p-chlorophenyl-1,1-dichloroethylene (DDE), and low levels of chlorinated dibenzofurans. The refined extract was dissolved in corn oil and administered intraperitoneally to weanling (day 20) female rats on days 20 and 21; rats were terminated on day 22. Limited data indicated possible hematopoietic effects, including neutrophilia. There were no changes in relative uterus, kidney, or adrenal gland weights between total doses of 3 to 96 mg/kg total PCB. Relative liver weights increased significantly at 36 mg/kg and activities of P450s 1A1 (as ethoxyresorufin O-dealkylase) and 2B (as pentoxyresorufin O-dealkylase) increased at 12 mg/kg and plateaued at 36 (P450 1A1) or 48 (P450 2b) mg/kg. Serum total thyroxine (T4) declined significantly at doses of 36 mg/kg and greater; thyroid follicular epithelial cells were significantly larger within the same dose range, but the follicular colloid area decreased to less than 60% control values at 12 mg/kg and remained at this size through 72 mg/kg. Maximum mobilization of T4 apparently occurred at 12 mg/kg and attenuated measured declines in circulating levels. Even though a large proportion of proven and probable estrogenic chlorobiphenyls (CBs) were present, the lower amounts of more potent antiestrogenic aryl hydrocarbon (Ah) receptor agonists and/or decreased responsiveness because of low serum T4 levels may have antagonized the uterotropic response.

Adrenal Glands↗
PubMed1995

Effects of gestational and lactational exposure to coplanar polychlorinated biphenyl (PCB) congeners or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on thyroid hormone concentrations in weanling rats.

Perinatal exposure to polychlorinated biphenyl (PCB) mixtures or to certain ortho-substituted PCB congeners dramatically reduces circulating thyroxine (T4) concentrations. It is not clear whether perinatal exposure to coplanar PCBs or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has a similar effect. In this study, time-mated Sprague-Dawley rats were dosed with 2 or 8 mg/kg/day PCB 77 (3,3',4,4'-tetrachlorobiphenyl), 0.25 or 1.00 micrograms/kg/day PCB 126 (3,3',4,4',5-pentachlorobiphenyl), 0.025 or 0.10 microgram/kg/day TCDD, or corn oil vehicle orally on gestation days 10-16. At weaning, plasma total T4 concentrations in PCB 77 and TCDD high-dose female pups were significantly depressed, but the changes were modest (84.4 and 79.6% of control, respectively). T4 concentrations in PCB 126 high-dose females and all high-dose males were also depressed slightly, but the changes were not statistically significant. UDP-Glucuronosyl transferase (UDP-GT) activity towards 4-nitrophenol was increased in all high-dose groups. Thus, the modest decreases in T4 could be due in part to increased T4 glucuronidation by UDP-GT. Triiodothyronine (T3) and thyroid stimulating hormone (TSH) concentrations were unchanged in all groups. In contrast to the minor changes in thyroid hormone status, liver microsomal ethoxyresorufin-O-deethylase (EROD) was markedly induced in all exposure groups and thymus weights were depressed in the high-dose groups. Because doses of coplanar PCBs or TCDD that caused marked induction of EROD activity had only minor effects on T4, we conclude that changes in thyroid hormone status at weaning are not among the more sensitive effects of perinatal exposure to these compounds.

Administration, Oral↗
PubMed1994

[Prevention of allergy in infants. A prospective study of 159 high-risk children].

A total of 105 infants at "high risk" for developing allergy born in 1988 were studied prospectively from birth to 18 months of age. The infants were recommended breastfeeding and/or hypoallergenic formula (Nutramigen or Profylac) combined with avoidance of solid foods the first six months of life. All mothers had unrestricted diet. Avoidance of daily exposure to tobacco smoking, furred pets and dust collecting materials in the bedroom was advised. This prevention group was compared to a control group consisting of 54 identically defined "high-risk" infants born in 1985 in the same area. All the infants had either severe single atopic predisposition combined with cord blood IgE > or = 0.5 KU/l or biparental atopic predisposition. The control group had unrestricted diet and was not advised about environmental factors. The cumulative incidence of atopic symptoms was significantly lower at 18 months in the prevention group (32%) compared with the control group (74%) (p < 0.01), due to reduced incidence of recurrent wheezing (13% versus 37%; p < 0.01), atopic dermatitis (14% versus 31%; p < 0.01), vomiting/diarrhoea (5% versus 20%; p < 0.01) and infantile colic (9% versus 24%; p < 0.01). The cumulative incidence of food-allergy was significantly lower in the prevention group (6% versus 17%; p < 0.05). In both high-risk groups exposure to daily tobacco smoking increased the risk of recurrent wheezing significantly (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Breast Feeding↗