PMID- 12417480
OWN - NLM
STAT- MEDLINE
DCOM- 20030225
LR  - 20181113
IS  - 0091-6765 (Print)
IS  - 0091-6765 (Linking)
VI  - 110
IP  - 11
DP  - 2002 Nov
TI  - Developmental neurotoxicity of chlorpyrifos: what is the vulnerable period?
PG  - 1097-103
AB  - Previously, we found that exposure of neonatal rats to chlorpyrifos (CPF) 
      produced brain cell damage and loss, with resultant abnormalities of synaptic 
      development. We used the same biomarkers to examine prenatal CPF treatment so as 
      to define the critical period of vulnerability. One group of pregnant rats 
      received CPF (subcutaneous injections in dimethyl sulfoxide vehicle) on 
      gestational days (GD) 17-20, a peak period of neurogenesis; a second group was 
      treated on GD9-12, the period of neural tube formation. In the GD17-20 group, the 
      threshold for a reduction in maternal weight gain was 5 mg/kg/day; at or below 
      that dose, there was no evidence (GD21) of general fetotoxicity as assessed by 
      the number of fetuses or fetal body and tissue weights. Above the threshold, 
      there was brain sparing (reduced body weight with an increase in brain/body 
      weight ratio) and a targeting of the liver (reduced liver/body weight). Indices 
      of cell packing density (DNA per gram of tissue) and cell number (DNA content) 
      similarly showed effects only on the liver; however, there were significant 
      changes in the protein/DNA ratio, an index of cell size, in fetal brain regions 
      at doses as low as 1 mg/kg, below the threshold for inhibition of fetal brain 
      cholinesterase (2 mg/kg). Indices of cholinergic synaptic development showed 
      significant CPF-induced defects but only at doses above the threshold for 
      cholinesterase inhibition. With earlier CPF treatment (GD9-12), there was no 
      evidence of general fetotoxicity or alterations of brain cell development at 
      doses up to the threshold for maternal toxicity (5 mg/kg), assessed on GD17 and 
      GD21; however, augmentation of cholinergic synaptic markers was detected at doses 
      as low as 1 mg/kg. Compared with previous work on postnatal CPF exposure, the 
      effects seen here required doses closer to the threshold for fetal weight loss; 
      this implies a lower vulnerability in the fetal compared with the neonatal brain. 
      Although delayed neurotoxic effects of prenatal CPF may emerge subsequently in 
      development, our results are consistent with the preferential targeting of late 
      developmental events such as gliogenesis, axonogenesis, and synaptogenesis.
FAU - Qiao, Dan
AU  - Qiao D
AD  - Department of Pharmacology and Cancer Biology, Duke University Medical Center, 
      Durham, North Carolina 27710, USA.
FAU - Seidler, Frederic J
AU  - Seidler FJ
FAU - Padilla, Stephanie
AU  - Padilla S
FAU - Slotkin, Theodore A
AU  - Slotkin TA
LA  - eng
GR  - ES10356/ES/NIEHS NIH HHS/United States
GR  - ES10387/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Environ Health Perspect
JT  - Environmental health perspectives
JID - 0330411
RN  - 0 (Insecticides)
RN  - 0 (Proteins)
RN  - 0 (Receptors, Muscarinic)
RN  - 9007-49-2 (DNA)
RN  - EC 2.3.1.6 (Choline O-Acetyltransferase)
RN  - EC 3.1.1.8 (Cholinesterases)
RN  - JCS58I644W (Chlorpyrifos)
SB  - IM
MH  - Animals
MH  - Body Weight
MH  - Brain/drug effects/*embryology
MH  - Chlorpyrifos/administration & dosage/*toxicity
MH  - Choline O-Acetyltransferase/analysis/pharmacology
MH  - Cholinesterases/analysis/pharmacology
MH  - DNA/analysis
MH  - Female
MH  - Fetal Death
MH  - Insecticides/administration & dosage/*toxicity
MH  - Pregnancy
MH  - *Prenatal Exposure Delayed Effects
MH  - Proteins/analysis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Muscarinic/drug effects
MH  - Weight Gain
PMC - PMC1241065
EDAT- 2002/11/06 04:00
MHDA- 2003/02/26 04:00
PMCR- 2002/11/01
CRDT- 2002/11/06 04:00
PHST- 2002/11/06 04:00 [pubmed]
PHST- 2003/02/26 04:00 [medline]
PHST- 2002/11/06 04:00 [entrez]
PHST- 2002/11/01 00:00 [pmc-release]
AID - sc271_5_1835 [pii]
AID - 10.1289/ehp.021101097 [doi]
PST - ppublish
SO  - Environ Health Perspect. 2002 Nov;110(11):1097-103. doi: 10.1289/ehp.021101097.