Exposure to the widely used fungicide Mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring

Marta Axelstad Petersen, Julie Boberg, Christine Lydia Nellemann, Maria Kristina Kiersgaard, Pernille Rosenskjold Jacobsen, Sofie Christiansen, Karin Sørig Hougaard, Ulla Hass

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Abstract

The widely used fungicide Mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal Mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100 or 150 mg Mancozeb/kg bw/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T4) levels were measured in dams during gestation. On PND 16 hormone levels and several organ weights were measured in the offspring, while motor activity, startle response and cognitive function was assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams, and was therefore reduced to 100 mg/kg bw/day in mid study. T4 levels showed a dose-dependent and significant decreased in dams from all three dose groups on GD 15, whereas offspring T4 levels, thyroid weights and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did however reduce T4 levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affect the developing brain.
Original languageEnglish
JournalToxicological Sciences
Volume120
Issue number2
Pages (from-to)439-446
ISSN1096-6080
DOIs
Publication statusPublished - 2011

Keywords

  • Behavior
  • Mancozeb
  • Developmental neurotoxicity
  • Rats thyroid-disrupting chemicals

Cite this

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title = "Exposure to the widely used fungicide Mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring",
abstract = "The widely used fungicide Mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal Mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100 or 150 mg Mancozeb/kg bw/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T4) levels were measured in dams during gestation. On PND 16 hormone levels and several organ weights were measured in the offspring, while motor activity, startle response and cognitive function was assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams, and was therefore reduced to 100 mg/kg bw/day in mid study. T4 levels showed a dose-dependent and significant decreased in dams from all three dose groups on GD 15, whereas offspring T4 levels, thyroid weights and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did however reduce T4 levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affect the developing brain.",
keywords = "Behavior, Mancozeb, Developmental neurotoxicity, Rats thyroid-disrupting chemicals",
author = "Petersen, {Marta Axelstad} and Julie Boberg and Nellemann, {Christine Lydia} and Kiersgaard, {Maria Kristina} and Jacobsen, {Pernille Rosenskjold} and Sofie Christiansen and Hougaard, {Karin S{\o}rig} and Ulla Hass",
year = "2011",
doi = "10.1093/toxsci/kfr006",
language = "English",
volume = "120",
pages = "439--446",
journal = "Toxicological Sciences",
issn = "1096-6080",
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Exposure to the widely used fungicide Mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring. / Petersen, Marta Axelstad; Boberg, Julie; Nellemann, Christine Lydia; Kiersgaard, Maria Kristina; Jacobsen, Pernille Rosenskjold; Christiansen, Sofie; Hougaard, Karin Sørig; Hass, Ulla.

In: Toxicological Sciences, Vol. 120, No. 2, 2011, p. 439-446.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Exposure to the widely used fungicide Mancozeb causes thyroid hormone disruption in rat dams but no behavioral effects in the offspring

AU - Petersen, Marta Axelstad

AU - Boberg, Julie

AU - Nellemann, Christine Lydia

AU - Kiersgaard, Maria Kristina

AU - Jacobsen, Pernille Rosenskjold

AU - Christiansen, Sofie

AU - Hougaard, Karin Sørig

AU - Hass, Ulla

PY - 2011

Y1 - 2011

N2 - The widely used fungicide Mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal Mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100 or 150 mg Mancozeb/kg bw/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T4) levels were measured in dams during gestation. On PND 16 hormone levels and several organ weights were measured in the offspring, while motor activity, startle response and cognitive function was assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams, and was therefore reduced to 100 mg/kg bw/day in mid study. T4 levels showed a dose-dependent and significant decreased in dams from all three dose groups on GD 15, whereas offspring T4 levels, thyroid weights and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did however reduce T4 levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affect the developing brain.

AB - The widely used fungicide Mancozeb has been shown to cause hypothyroxinemia and other adverse effects on the thyroid hormone system in adult experimental animals. In humans, hypothyroxinemia early in pregnancy is associated with adverse effects on the developing nervous system and can lead to impaired cognitive function and motor development in children. The aim of the present study was therefore to assess whether perinatal Mancozeb exposure would cause developmental neurotoxicity in rats. Groups of 9-21 time-mated Wistar rats were dosed with 0, 50, 100 or 150 mg Mancozeb/kg bw/day by gavage from gestation day (GD) 7 to postnatal day (PND) 16, and total thyroxine (T4) levels were measured in dams during gestation. On PND 16 hormone levels and several organ weights were measured in the offspring, while motor activity, startle response and cognitive function was assessed in the adult offspring. The dose of 150 mg/kg/day caused neurotoxicity in the pregnant dams, and was therefore reduced to 100 mg/kg bw/day in mid study. T4 levels showed a dose-dependent and significant decreased in dams from all three dose groups on GD 15, whereas offspring T4 levels, thyroid weights and histology were unaffected on PND 16. No effects on reproductive organ weights were seen, and no behavioral changes were observed. Taken together, these results indicate that in rats, moderate maternal hypothyroxinemia during gestation does not necessarily lead to hyperactivity or reduced special learning abilities in the offspring. Mancozeb exposure did however reduce T4 levels in dams and may therefore still be a potential contributor to thyroid disruption in humans and in result adversely affect the developing brain.

KW - Behavior

KW - Mancozeb

KW - Developmental neurotoxicity

KW - Rats thyroid-disrupting chemicals

U2 - 10.1093/toxsci/kfr006

DO - 10.1093/toxsci/kfr006

M3 - Journal article

VL - 120

SP - 439

EP - 446

JO - Toxicological Sciences

JF - Toxicological Sciences

SN - 1096-6080

IS - 2

ER -