PMID- 30738146
OWN - NLM
STAT- MEDLINE
DCOM- 20200520
LR  - 20200520
IS  - 1872-9738 (Electronic)
IS  - 0892-0362 (Linking)
VI  - 72
DP  - 2019 Mar-Apr
TI  - Developmental neurotoxicity of inorganic arsenic exposure in Sprague-Dawley rats.
PG  - 49-57
LID - S0892-0362(18)30130-2 [pii]
LID - 10.1016/j.ntt.2019.01.007 [doi]
AB  - High levels of inorganic arsenic (iAs) exposure are associated with severe health 
      effects. Less clear are effects of lower exposure levels on neurodevelopment. 
      Relative to maternal intake, there is limited lactational transfer of arsenic in 
      humans or rodents, yet there are few rodent studies which directly exposed 
      preweaning animals. To more clearly determine iAs developmental neurotoxicity, 28 
      pregnant Sprague-Dawley rats were exposed to arsenate (AsV) via drinking water 
      (0, 23.6, 47.7, 71.0 ppm) (n = 5-7/group) from gestational day (GD) 6 through GD 
      22 with targeted doses of 0, 2.33, 4.67, 7.00 mg/kg/day, respectively. Offspring 
      were dosed by gavage daily with the same mg/kg AsV dose as intended for their dam 
      from postnatal day (PND) 1 to 21. Gestational water intake was reduced at all AsV 
      doses, but returned to control levels on lactational day (LD) 1 when control 
      water was returned. Gestational body weight was reduced only at the highest dose 
      on GD 22 and lactational body weight was unaffected. Food intake was unaffected. 
      iAs exposure did not alter offspring body weight (PNDs 1-21) or age at fur 
      development and bilateral ear opening. Incisor eruption, however, was 
      significantly delayed in offspring of the 4.67 and 7.00 mg/kg groups. Further, 
      all iAs groups were significantly delayed in bilateral eye opening. Righting 
      reflex (PNDs 3-6) was unaffected, while slant board performance (PNDs 8-11) was 
      significantly poorer at the highest dose. Brains of culled pups (PND 1) showed 
      dose-dependent increases of iAs. There were no significant AsV-related effects on 
      PND 21 brain regional concentrations of dopamine, DOPAC, HVA, 5-HT or 5-HIAA. 
      These hazard identification results will guide the study designs of developmental 
      iAs exposure at human-relevant levels essential for risk-assessment.
CI  - Published by Elsevier Inc.
FAU - Moore, Christopher L
AU  - Moore CL
AD  - Division of Neurotoxicology, National Center for Toxicological Research (NCTR), 
      FDA, Jefferson, AR 72079, United States of America.
FAU - Flanigan, Timothy J
AU  - Flanigan TJ
AD  - Division of Neurotoxicology, National Center for Toxicological Research (NCTR), 
      FDA, Jefferson, AR 72079, United States of America.
FAU - Law, Charles D
AU  - Law CD
AD  - Division of Neurotoxicology, National Center for Toxicological Research (NCTR), 
      FDA, Jefferson, AR 72079, United States of America.
FAU - Loukotkova, Lucie
AU  - Loukotkova L
AD  - Division of Biochemical Toxicology, NCTR, FDA, Jefferson, AR 72079, United States 
      of America.
FAU - Woodling, Kellie A
AU  - Woodling KA
AD  - Division of Biochemical Toxicology, NCTR, FDA, Jefferson, AR 72079, United States 
      of America.
FAU - da Costa, Goncalo Gamboa
AU  - da Costa GG
AD  - Division of Biochemical Toxicology, NCTR, FDA, Jefferson, AR 72079, United States 
      of America.
FAU - Fitzpatrick, Suzanne C
AU  - Fitzpatrick SC
AD  - Office of the Center Director, Center for Food Safety & Applied Nutrition, FDA, 
      College Park, MD 20740, United States of America.
FAU - Ferguson, Sherry A
AU  - Ferguson SA
AD  - Division of Neurotoxicology, National Center for Toxicological Research (NCTR), 
      FDA, Jefferson, AR 72079, United States of America. Electronic address: 
      Sherry.Ferguson@fda.hhs.gov.
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20190206
PL  - United States
TA  - Neurotoxicol Teratol
JT  - Neurotoxicology and teratology
JID - 8709538
RN  - 0 (Arsenates)
RN  - 0 (Environmental Pollutants)
RN  - N7CIZ75ZPN (arsenic acid)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Arsenates/pharmacokinetics/*toxicity
MH  - Behavior, Animal/*drug effects
MH  - Brain/drug effects/growth & development/metabolism
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Environmental Pollutants/pharmacokinetics/*toxicity
MH  - Female
MH  - Male
MH  - Maternal Exposure
MH  - Neurotoxicity Syndromes/*etiology/psychology
MH  - Organ Size/drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects/*chemically induced/psychology
MH  - Rats, Sprague-Dawley
MH  - Reflex, Righting/drug effects
OTO - NOTNLM
OT  - Arsenate
OT  - Developmental toxicity
OT  - Drinking water
OT  - Inorganic arsenic
OT  - Neurobehavior
OT  - Rat
EDAT- 2019/02/10 06:00
MHDA- 2020/05/21 06:00
CRDT- 2019/02/10 06:00
PHST- 2018/09/28 00:00 [received]
PHST- 2018/12/07 00:00 [revised]
PHST- 2019/01/31 00:00 [accepted]
PHST- 2019/02/10 06:00 [pubmed]
PHST- 2020/05/21 06:00 [medline]
PHST- 2019/02/10 06:00 [entrez]
AID - S0892-0362(18)30130-2 [pii]
AID - 10.1016/j.ntt.2019.01.007 [doi]
PST - ppublish
SO  - Neurotoxicol Teratol. 2019 Mar-Apr;72:49-57. doi: 10.1016/j.ntt.2019.01.007. Epub 
      2019 Feb 6.