Effects of bromodichloromethane on ex vivo and in vitro luteal function and bromodichloromethane tissue dosimetry in the pregnant F344 rat

Bielmeier, Susan R.; Murr, Ashley S.; Best, Deborah S.; Harrison, Randy; Pegram, Rex A.; Goldman, Jerome M.; Narotsky, Michael G.

doi:10.1016/j.tiv.2007.01.017

Cited by 15 publications

(8 citation statements)

References 27 publications

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“…Brominated THM is thought to present a greater health risk than CH, primarily because of differences in their metabolism and toxicokinetics 28 29. In addition, BDCM can disrupt syncytiotrophoblast formation and inhibit chorionic gonadotrophin secretion in vitro 29.…”

Section: Discussionmentioning

confidence: 99%

Risk of congenital anomalies in relation to the uptake of trihalomethane from drinking water during pregnancy

et al. 2013

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ObjectivesCongenital anomalies have been inconsistently associated with maternal crude estimated exposure to drinking water trihalomethane (THM). We investigated the relationship between individual THM uptake during the first trimester of pregnancy and congenital anomalies.MethodsWe estimated maternal THM uptake for 3074 live births using residential tap water concentrations, drinking water ingestion, showering and bathing, and uptake factors of THM in the blood. Multiple logistic regression was used to investigate the association of THM exposure with congenital anomalies.ResultsWe observed no statistically significant relationships between congenital anomalies and the total THM internal dose. We found little indication of a dose-response relationship for brominated THM and congenital heart anomalies. The relationship was statistically significant for bromodichloromethane (BDCM) (OR=2.16, 95% CI 1.05 to 4.46, highest vs lowest tertile) during the first month of pregnancy. During the first trimester of pregnancy, the probability of developing heart anomalies increased for every 0.1 μg/d increase in the BDCM and for every 0.01 μg/d increase in the internal dibromochloromethane (DBCM) dose (OR 1.70, 95% CI 1.09 to 2.66, and OR 1.25, 95% CI 1.01 to 1.54, respectively). A dose-response relationship was evident for musculoskeletal anomalies and DBCM exposure during the first and second months of pregnancy, while BDCM exposure tended to increase the risk of urogenital anomalies.ConclusionsThis study shows some evidence for an association between the internal dose of THM and the risk of congenital anomalies. In particular, increased prenatal exposure to brominated THM might increase the risk of congenital heart and musculoskeletal anomalies.

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Section: Discussionmentioning

confidence: 99%

Risk of congenital anomalies in relation to the uptake of trihalomethane from drinking water during pregnancy

et al. 2013

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“…Human, DW, epi (Waller et al, 1998) Human, DW, epi, time to pregnancy as indicator of possible early pregnancy loss (MacLehose et al, 2008) In the rat, BDCM decreases serum LH, resulting in decreased serum progesterone; F344 has less constitutive LH than SD, LH in rats is analogous to hCG in humans; hCG or progesterone prevented full-litter resorption in rats treated with BDCM (Narotsky and Laffan, 2004;Bielmeier et al, 2001Bielmeier et al, , 2002Bielmeier et al, , 2004Bielmeier et al, , 2007 Human, DW, epi (Savitz et al, 2005(Savitz et al, , 2006 SD rat G-aqueous emulphor (Bielmeier et al, 2001(Bielmeier et al, , 2002 BDCM inhibited hCG-stimulated progesterone secretion by rat corpora lutea in vitro (Bielmeier et al, 2007) F344 rat, G-aqueous emulphor (Bielmeier et al, 2001(Bielmeier et al, , 2004 SD rat, DW (Christian et al, 2001a) BDCM inhibited differentiation of cultured human placental trophoblast cells and decreased hCG secretion and intracellular hCG (Chen et al, 2003(Chen et al, , 2004 F344 rat, G-aqueous emulphor-slight but not significant increase (Narotsky et al, 1997a) SD rat, rabbit, DW, fertility not affected (Christian et al, 2002a) Rabbit, DW, limited data suggest BDCM reaches placenta and fetus (Christian et al, 2001b) F344 rat, G-corn oil (Narotsky et al, 1997a) SD rat, DW (NTP, National Toxicology Program, 1998a) Generally, toxicity may be mediated through metabolism to reactive and toxic intermediates (ILSI, 1999) F344 rat, G-corn oil (Narotsky et al, 1992) Dibromochloromethane -Human, DW, epi (Waller et al, 1998) Generally, toxicity may be mediated through metabolism to reactive and toxic intermediates (ATSDR, 2003;ILSI, 1999) Human, DW, epi (Savitz et al, 2005(Savitz et al, , 2006 SD rat, DW (NTP, National Toxicology Program, 1996) Bromoform F344 rat, G-corn oil, developmental toxicity screen…”

Section: Dbp Exposure Measurementioning

confidence: 99%

Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action

Colman

Rice

Wright

et al. 2011

Toxicology and Applied Pharmacology

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Reactions between chemicals used to disinfect drinking water and compounds present in source waters produce chemical mixtures containing hundreds of disinfection byproducts (DBPs). Although the results have been somewhat inconsistent, some epidemiological studies suggest associations may exist between DBP exposures and adverse developmental outcomes. The potencies of individual DBPs in rodent and rabbit developmental bioassays suggest that no individual DBP can account for the relative risk estimates reported in the positive epidemiologic studies, leading to the hypothesis that these outcomes could result from the toxicity of DBP mixtures. As a first step in a mixtures risk assessment for DBP developmental effects, this paper identifies developmentally toxic DBPs and examines data relevant to the mode of action (MOA) for DBP developmental toxicity. We identified 24 developmentally toxic DBPs and four adverse developmental outcomes associated with human DBP exposures: spontaneous abortion, cardiovascular defects, neural tube defects, and low birth weight infancy. A plausible MOA, involving hormonal disruption of pregnancy, is delineated for spontaneous abortion, which some epidemiologic studies associate with total trihalomethane and bromodichloromethane exposures. The DBP data for the other three outcomes were inadequate to define key MOA steps.

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“…Although this inbred strain is not generally considered appropriate for reproductive toxicity testing, unlike Sprague–Dawley rats, it is sensitive to toxicant‐induced full‐litter resorption, that is, pregnancy loss. When administered by gavage, DBPs such as bromodichloromethane (Bielmeier et al., , , ), bromoform (Narotsky et al., , ), and defined mixtures of regulated trihalomethanes (THM4) and/or haloacetic acids (HAA5) (Narotsky et al., ) have been shown to cause pregnancy loss in F344 rats. To our knowledge, complex mixtures of DBPs have never been previously tested in drinking water for effects on pregnancy maintenance in this strain.…”

Section: Discussionmentioning

confidence: 99%

“…Both of these adverse outcomes have been associated with individual DBPs in rodents exposed via gavage. Bromodichloromethane causes pregnancy loss by a luteinizing hormone (LH)‐mediated mode of action (Bielmeier et al., , , ), whereas di‐ and trichloroacetic acids cause eye defects (Smith et al., , ). Defined mixtures of DBPs also cause pregnancy loss and eye malformations in F344 rats (Narotsky et al., ).…”

Section: Introductionmentioning

confidence: 99%

Developmental Toxicity Evaluations of Whole Mixtures of Disinfection By‐products using Concentrated Drinking Water in Rats: Gestational and Lactational Effects of Sulfate and Sodium

Narotsky

Pressman

Miltner

et al. 2012

Birth Defects Research Pt B

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A developmental toxicity bioassay was used in three experiments to evaluate water concentrates for suitability in multigenerational studies. First, chlorinated water was concentrated 135-fold by reverse osmosis; select lost disinfection by-products were spiked back. Concentrate was provided as drinking water to Sprague-Dawley and F344 rats from gestation day 6 to postnatal day 6. Maternal serum levels of luteinizing hormone on gestation day 10 were unaffected by treatment for both strains. Treated dams had increased water consumption, and increased incidences of polyuria, diarrhea, and (in Sprague-Dawley rats) red perinasal staining. Pup weights were reduced. An increased incidence of eye defects was seen in F344 litters. Chemical analysis of the concentrate revealed high sodium (6.6 g/l) and sulfate (10.4 g/l) levels. To confirm that these chemicals caused polyuria and osmotic diarrhea, respectively, Na₂SO₄ (5-20 g/l) or NaCl (16.5 g/l) was provided to rats in drinking water. Water consumption was increased at 5- and 10-g Na₂SO₄/l and with NaCl. Pup weights were reduced at 20-g Na₂SO₄/l. Dose-related incidences and severity of polyuria and diarrhea occurred in Na₂SO₄-treated rats; perinasal staining was seen at 20 g/l. NaCl caused polyuria and perinasal staining, but not diarrhea. Subsequently, water was concentrated ∼120-fold and sulfate levels were reduced by barium hydroxide before chlorination, yielding lower sodium (≤1.5 g/l) and sulfate (≤2.1 g/l) levels. Treatment resulted in increased water consumption, but pup weight and survival were unaffected. There were no treatment-related clinical findings, indicating that mixtures produced by the second method are suitable for multigenerational testing.

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Effects of bromodichloromethane on ex vivo and in vitro luteal function and bromodichloromethane tissue dosimetry in the pregnant F344 rat

Cited by 15 publications

References 27 publications

Risk of congenital anomalies in relation to the uptake of trihalomethane from drinking water during pregnancy

Risk of congenital anomalies in relation to the uptake of trihalomethane from drinking water during pregnancy

Identification of developmentally toxic drinking water disinfection byproducts and evaluation of data relevant to mode of action

Developmental Toxicity Evaluations of Whole Mixtures of Disinfection By‐products using Concentrated Drinking Water in Rats: Gestational and Lactational Effects of Sulfate and Sodium

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