The weeks shown in color represent the start and end points of chemical exposure for each study.

Study Results Study Details References

Results for Chlorpyrifos

Increased 5HT receptor binding markers over all brain regions studied at post-natal day 5; increased 5HT receptor binding in the forebrain at post-natal day 10

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Aldridge JE, Seidler FJ, Meyer A, Thillai I, Slotkin TA. 2003. Serotonergic systems targeted by developmental exposure to chlorpyrifos: Effects during different critical periods. Environ Health Perspect 111(14):1736-1743.
Study Results Study Details References

Results for Chlorpyrifos

Increased 5HT receptor binding markers over all brain regions studied at post-natal day 5; decreased 5HT receptor binding in the brainstem at post-natal day 10

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Aldridge JE, Seidler FJ, Meyer A, Thillai I, Slotkin TA. 2003. Serotonergic systems targeted by developmental exposure to chlorpyrifos: Effects during different critical periods. Environ Health Perspect 111(14):1736-1743.
Study Results Study Details References

Results for Chlorpyrifos

Increased 5HT receptor (type 1A and 2) binding in the cerebral cortex of males; increased overall 5HT binding markers in the midrain of males; decreased 5HTT binding in females

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 60 days of age

Reference [PubMed Link]
Aldridge JE, Seidler FJ, Slotkin TA. 2004. Developmental exposure to chlorpyrifos elicits sex-selective alterations of serotonergic synaptic function in adulthood: Critical periods and regional selectivity for effects on the serotonin transporter, receptor subtypes, and cell signaling. Environ Health Perspect 112(2):148-155.
Study Results Study Details References

Results for Chlorpyrifos

Increased 5HT receptor (type 1A and 2) and 5HTT binding in the brainstem; decreased activity of adenylyl cyclase in the brainstem of females

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 60 days of age

Reference [PubMed Link]
Aldridge JE, Seidler FJ, Slotkin TA. 2004. Developmental exposure to chlorpyrifos elicits sex-selective alterations of serotonergic synaptic function in adulthood: Critical periods and regional selectivity for effects on the serotonin transporter, receptor subtypes, and cell signaling. Environ Health Perspect 112(2):148-155.
Study Results Study Details References

Results for Chlorpyrifos

Increased time spent in the open arms of the elevated plus maze by males, eliminating sexual differences; increased locomotor activity of males in the elevated plus maze in adulthood; decreased chocholate preference ratio across the two sexes at post-natal day 54; increased number of reference memory errors in males in a radial arm maze test in adulthood; increased number of errors across the two memory measures (working and reference memory) in males, while the errors decreased for females, in adulthood; increased working and reference memory errors at 0.5 and 2 mg/kg of ketanserine (a 5HT2 receptor antagonist) and increased working memory errors at 1 mg/kg of ketanserine in adulthood

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal days 52 through 120

Reference [PubMed Link]
Aldridge JE, Levin ED, Seidler FJ, Slotkin TA. 2005. Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression. Environ Health Perspect 113(5):527-531.
Study Results Study Details References

Results for Chlorpyrifos

Increased percent time spent in open arms and number of center crossings in an elevated plus maze among males; decreased chocolate milk to water preference ratio in males and females; decreased working memory errors during radial arm maze among females; increased reference memory errors for male rats in 16-arm radial maze; increased reference and memory errors for male and females after injections of ketanserin ( a 5HT2 receptor antagonist) at the end of 18 training sessions

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected sub-cutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 52 through 119 days of age

Reference [PubMed Link]
Aldridge JE, Levin ED, Seidler FJ, Slotkin TA. 2005. Developmental exposure of rats to chlorpyrifos leads to behavioral alterations in adulthood, involving serotonergic mechanisms and resembling animal models of depression. Environ Health Perspect 113(5):527-531.
Study Results Study Details References

Results for Chlorpyrifos

Decreased 5HT content in female rat cerebral cortex and midbrain; increased 5HT turnover in male and female rats cerebral cortex, midbrain, and striatum

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected sub-cutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 60 days of age

Reference [PubMed Link]
Aldridge JE, Meyer A, Seidler FJ, Slotkin TA. 2005. Alterations in central nervous system serotonergic and dopaminergic synaptic activity in adulthood after prenatal or neonatal chlorpyrifos exposure. Environ Health Perspect 113(8):1027-1031.
Study Results Study Details References

Results for Chlorpyrifos

Decreased 5HT content in female hippocampus; increased 5HT turnover in male and female hippocampus

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected sub-cutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 60 days of age

Reference [PubMed Link]
Aldridge JE, Meyer A, Seidler FJ, Slotkin TA. 2005. Alterations in central nervous system serotonergic and dopaminergic synaptic activity in adulthood after prenatal or neonatal chlorpyrifos exposure. Environ Health Perspect 113(8):1027-1031.
Study Results Study Details References

Results for Chlorpyrifos

Decreased brain region weights for combined brainstem, forebrain and cerebellum at 5 mg/kg on post-natal day 5

Subjects: Unspecified strain rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 or 5.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 through 20

Reference [PubMed Link]
Campbell CG, Seidler FJ, Slotkin TA. 1997. Chlorpyrifos interferes with cell development in rat brain regions. Brain Res Bull 43(2):179-189.
Study Results Study Details References

Results for Chlorpyrifos

Inhibition of DNA synthesis with a marked effect at 24 hours after last CPF injection in the forebrain

Subjects: Unspecified rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: after 4 hours and 24 hours from last CPF injection

Reference [PubMed Link]
Dam K, Seidler FJ, Slotkin TA. 1998. Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration. Developmental Brain Research 108(1-2):39-45.
Study Results Study Details References

Results for Chlorpyrifos

Decreased brain region weights for combined brainstem, forebrain and cerebellum at 5 mg/kg on post-natal day 5; increased DNA and protein concentration and DNA content in the cerebellum on post-natal day 5 at 1 mg/kg; decreased DNA concentration, DNA content and protein concentration in the cerebellum on post-natal day 10 at 1 mg/kg; increased DNA and protein concentration in the cerebellum on post-natal day 5 at 5 mg/kg; decreased DNA concentration and content in the brainstem on post-natal day 5 at 5 mg/kg; increased protein to DNA ratio in the brainstem on post-natal day 5 at 5 mg/kg; increased DNA concentration, DNA content and protein concentration in the brainstem on post-natal day 10 at 1 mg/kg; increased DNA concentration on post-natal day 5 at 1 mg/kg

Subjects: Unspecified strain rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 or 5.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Campbell CG, Seidler FJ, Slotkin TA. 1997. Chlorpyrifos interferes with cell development in rat brain regions. Brain Res Bull 43(2):179-189.
Study Results Study Details References

Results for Chlorpyrifos

Inhibition of DNA synthesis with a marked effect at 24 hours after last CPF injection in the brainstem

Subjects: Unspecified rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: after 4 hours and 24 hours from last CPF injection

Reference [PubMed Link]
Dam K, Seidler FJ, Slotkin TA. 1998. Developmental neurotoxicity of chlorpyrifos: delayed targeting of DNA synthesis after repeated administration. Developmental Brain Research 108(1-2):39-45.
Study Results Study Details References

Results for Chlorpyrifos

Decreased choline acetyltransferase binding characteristics in the forebrain; increased turnover of norepinephrine in the forebrain across the two ages; increased turnover of dopamine in the forebrain with a marked effect on post-natal day 10;

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Dam K, Garcia SJ, Seidler FJ, Slotkin TA. 1999. Neonatal chlorpyrifos exposure alters synaptic development and neuronal activity in cholinergic and catecholaminergic pathways. Developmental Brain Research 116(1):9-20.
Study Results Study Details References

Results for Chlorpyrifos

Increased turnover (transmitter utilization) of dopamine in the brainstem with a marked effect on post-natal day 5; increased turnover of norepinephrine in the cerebellum with a marked effect on post-natal day 5

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Dam K, Garcia SJ, Seidler FJ, Slotkin TA. 1999. Neonatal chlorpyrifos exposure alters synaptic development and neuronal activity in cholinergic and catecholaminergic pathways. Developmental Brain Research 116(1):9-20.
Study Results Study Details References

Results for Chlorpyrifos

Increased time to reflex righting and decreased negative geotaxis in females; decreased locomotor activity and rearing in males

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 4 through 30 days of age

Reference [PubMed Link]
Dam K, Seidler FJ, Slotkin TA. 2000. Chlorpyrifos exposure during a critical neonatal period elicits gender-selective deficits in the development of coordination skills and locomotor activity. Developmental Brain Research 121(2):179-187.
Study Results Study Details References

Results for Chlorpyrifos

Increased levels of c-Fos mRNA in the forebrain on post-natal day 5

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Dam K, Seidler FJ, Slotkin TA. 2003. Transcriptional biomarkers distinguish between vulnerable periods for developmental neurotoxicity of chlorpyrifos: Implications for toxicogenomics. Brain Res Bull 59(4):261-265.
Study Results Study Details References

Results for Chlorpyrifos

Decreased levels of glial fibrillary acidic protein (GFAP) in the cerebellum of males at post-natal day 5

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal days 5, 10 and 30

Reference [PubMed Link]
Garcia SJ, Seidler FJ, Qiao D, Slotkin TA. 2002. Chlorpyrifos targets developing glia: effects on glial fibrillary acidic protein. Brain Res Dev Brain Res 133(2):151-161.
Study Results Study Details References

Results for Chlorpyrifos

Increased concentration of RNA in the forebrain on post-natal day 5; decreased concentration and content of RNA in the forebrain on post-natal day 10;

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Johnson DE, Seidler FJ, Slotkin TA. 1998. Early biochemical detection of delayed neurotoxicity resulting from developmental exposure to chlorpyrifos. Brain Res Bull 45(2):143-147.
Study Results Study Details References

Results for Chlorpyrifos

Decreased concentration and content of RNA in the brainstem

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Johnson DE, Seidler FJ, Slotkin TA. 1998. Early biochemical detection of delayed neurotoxicity resulting from developmental exposure to chlorpyrifos. Brain Res Bull 45(2):143-147.
Study Results Study Details References

Results for Chlorpyrifos

Decreased working memory and reference memory errors in females; increased initial working memory and reference memory errors in males

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 4 through 17 weeks of age

Reference [PubMed Link]
Levin ED, Addy N, Nakajima A, Christopher NC, Seidler FJ, Slotkin TA. 2001. Persistent behavioral consequences of neonatal chlorpyrifos exposure in rats. Developmental Brain Research 130(1):83-89.
Study Results Study Details References

Results for Chlorpyrifos

Increased activity of adenylyl cyclase in response to forskolin and Mn2+ in the cerebral cortex

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 60 days of age

Reference [PubMed Link]
Meyer A, Seidler FJ, Aldridge JE, Tate CA, Cousins MM, Slotkin TA. 2004. Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure. Environ Health Perspect 112(3):295-301.
Study Results Study Details References

Results for Chlorpyrifos

Increased activity of adenylyl cyclase in response to isoproterenol in the brainstem; decreased basal and isoprotenerol-stimulated activity in males in the cerebellum; increased basal and stimulated activity of adelylyl cyclase in the cerebellum of females

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 60 days of age

Reference [PubMed Link]
Meyer A, Seidler FJ, Aldridge JE, Tate CA, Cousins MM, Slotkin TA. 2004. Critical periods for chlorpyrifos-induced developmental neurotoxicity: alterations in adenylyl cyclase signaling in adult rat brain regions after gestational or neonatal exposure. Environ Health Perspect 112(3):295-301.
Study Results Study Details References

Results for Chlorpyrifos

Decreased paroxetine binding to the presynaptic 5HT high-affinity transporter in the forebrain of males with increased binding in females on post-natal day 5

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Raines KW, Seidler FJ, Slotkin TA. 2001. Alterations in serotonin transporter expression in brain regions of rats exposed neonatally to chlorpyrifos. Developmental Brain Research 130(1):65-72.
Study Results Study Details References

Results for Chlorpyrifos

Decreased paroxetine binding to the presynaptic 5HT high-affinity transporter in the brainstem

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Raines KW, Seidler FJ, Slotkin TA. 2001. Alterations in serotonin transporter expression in brain regions of rats exposed neonatally to chlorpyrifos. Developmental Brain Research 130(1):65-72.
Study Results Study Details References

Results for Chlorpyrifos

Decreased cholinesterase activity; decreased total and M1/M3 muscarinic acetylcholine receptor levels; decreased high affinity choline uptake transporter levels

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.5 mg/kg bw/d

Other doses tested: increasing dose from 1.5 to 6 mg/kg between days 1 and 21

Route of administration: dissolved in corn oil and delivered through gavage

Exposure duration: post-natal day 1 – post-natal day 21 (comparable to human prenatal development from approximately day 1 of week 20 to beyond birth)

Age of measurement: 6 through 30 days of age

Reference [PubMed Link]
Richardson JR, Chambers JE. 2005. Effects of repeated oral postnatal exposure to chlorpyrifos on cholinergic neurochemistry in developing rats. Toxicol Sci 84(2):352-359.
Study Results Study Details References

Results for Chlorpyrifos

Decreased binding of hemicolinium-3 (HC-3), a cholinergic marker, in the midbrain; decreased levels of HC-3 and choline acetyltransferase (ChAT) in the striatum of females

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal days 30 and 60

Reference [PubMed Link]
Slotkin TA, Cousins MM, Tate CA, Seidler FJ. 2001. Persistent cholinergic presynaptic deficits after neonatal chlorpyrifos exposure. Brain Res 902(2):229-243.
Study Results Study Details References

Results for Chlorpyrifos

Decreased levels of ChAT in the hippocampus of females at post-natal day 30 and in both sexes at post-natal dat 60; decreased HC3 binding in the hippocampus across post-natal day 30 and 60

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal days 30 and 60

Reference [PubMed Link]
Slotkin TA, Cousins MM, Tate CA, Seidler FJ. 2001. Persistent cholinergic presynaptic deficits after neonatal chlorpyrifos exposure. Brain Res 902(2):229-243.
Study Results Study Details References

Results for Chlorpyrifos

Increased levels of dopamine in the cerebral cortex on post-natal day 30 while decreased on post-natal day 60; decreased dopamine turnover in the cerebral cortex of males; increased levels of dopamine on post-natal day 60 in the striatum; increased turn-over of norepinephrine in males while decreased in females striatum on post-natala day 60; increased dopamine turn-over in the midbrain and striatum

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 30 and 60

Reference [PubMed Link]
Slotkin TA, Tate CA, Cousins MM, Seidler FJ. 2002. Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure. Developmental Brain Research 133(2):163-173.
Study Results Study Details References

Results for Chlorpyrifos

Decreased norepinephrine δ-turn-over in the hippocampus in response to nicotine challenge

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 30 and 60

Reference [PubMed Link]
Slotkin TA, Tate CA, Cousins MM, Seidler FJ. 2002. Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure. Developmental Brain Research 133(2):163-173.
Study Results Study Details References

Results for Chlorpyrifos

Increased norepinephrine δ-turn-over in the cerebellum of males on post-natal day 30 in response to nicotine challenge with decreases in males and females at post-natal day 60

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 30 and 60

Reference [PubMed Link]
Slotkin TA, Tate CA, Cousins MM, Seidler FJ. 2002. Functional alterations in CNS catecholamine systems in adolescence and adulthood after neonatal chlorpyrifos exposure. Developmental Brain Research 133(2):163-173.
Study Results Study Details References

Results for Chlorpyrifos

Decreased α4β2nAChR receptor binding in the cerebellum on post-natal day 10

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5 and 10

Reference [PubMed Link]
Slotkin TA, Southard MC, Adam SJ, Cousins MM, Seidler FJ. 2004. 7 Nicotinic acetylcholine receptors targeted by cholinergic developmental neurotoxicants: Nicotine and chlorpyrifos. Brain Res Bull 64(3):227-235.
Study Results Study Details References

Results for Chlorpyrifos

Increased levels of 5HTT binding in the cerebral cortex of females; increased levels of 5HT1A , 5HT2 and 5HTT binding in the striatum of males while decreased in the striatum of females with a marked effects on 5HT1A; increased levels of 5HT1A and 5HT2 binding in the midbrain of males

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 5 months of age

Reference [PubMed Link]
Slotkin TA, Seidler FJ. 2005. The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent. Developmental Brain Research 158(1-2):115-119.
Study Results Study Details References

Results for Chlorpyrifos

Increased levels of 5HT1A , 5HT2 and 5HTT binding in the brainstem of males

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 5 months of age

Reference [PubMed Link]
Slotkin TA, Seidler FJ. 2005. The alterations in CNS serotonergic mechanisms caused by neonatal chlorpyrifos exposure are permanent. Developmental Brain Research 158(1-2):115-119.
Study Results Study Details References

Results for Chlorpyrifos

General decrease of fibroblast growth factor 2 (fgf2) across regions under study; decreased fgf11 and fgf20 in the forebrain

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected sub-cutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5

Reference [PubMed Link]
Slotkin TA, Seidler FJ, Fumagalli F. 2007. Exposure to organophosphates reduces the expression of neurotrophic factors in neonatal rat brain regions: Similarities and differences in the effects of chlorpyrifos and diazinon on the fibroblast growth factor superfamily. Environ Health Perspect 115(6):909-916.
Study Results Study Details References

Results for Chlorpyrifos

General decrease of fibroblast growth factor 2 (fgf2) across the regions under study; decreased expression of fgf22; increased expression of fibroblast growth factor receptor 4 (fgfr4 )

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected sub-cutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5

Reference [PubMed Link]
Slotkin TA, Seidler FJ, Fumagalli F. 2007. Exposure to organophosphates reduces the expression of neurotrophic factors in neonatal rat brain regions: Similarities and differences in the effects of chlorpyrifos and diazinon on the fibroblast growth factor superfamily. Environ Health Perspect 115(6):909-916.
Study Results Study Details References

Results for Chlorpyrifos

Decreased forebrain basal adenylyl cyclase activity in the presence of G-proteins, decreased fluoride-stimulated adenylyl cyclase activity, and decreased Forskolin -Mn2 adenylyl cyclase activity, all at 10 days of age at 1 mg/kg; decreased isoproterenol-stimulated adenylyl cyclase activity at 10 days of age at 1 mg/kg; decreased forebrain M1 receptor binding at 5 and 10 days of age at 1 mg/kg; decreased forebrain weight, M1 and M2 receptor binding at 5 days of age at 5 mg/kg

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 or 5.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected sub-cutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 5 and 10 days of age

Reference [PubMed Link]
Song X, Seidler FJ, Saleh JL, Zhang J, Padilla S, Slotkin TA. 1997. Cellular mechanisms for developmental toxicity of chlorpyrifos: Targeting the adenylyl cyclase signaling cascade. Toxicology & Applied Pharmacology 145(1):158-174.
Study Results Study Details References

Results for Chlorpyrifos

Decreased brainstem cholinesterase activity at 1 mg/kg; decreased cerebellum basal adenylyl cyclase activity at 10 days of age at 1 mg/kg and at 5 days of age at 5 mg/kg; increased cerebellum basal adenylyl cyclase activity in the presence of carbachol at 5 days of age at 1 mg/kg; decreased cerebellum basal adenylyl cyclase activity in the absence of GTP at 5 days of age at 5 mg/kg

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 or 5.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected sub-cutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: 5 and 10 days of age

Reference [PubMed Link]
Song X, Seidler FJ, Saleh JL, Zhang J, Padilla S, Slotkin TA. 1997. Cellular mechanisms for developmental toxicity of chlorpyrifos: Targeting the adenylyl cyclase signaling cascade. Toxicology & Applied Pharmacology 145(1):158-174.
Study Results Study Details References

Results for Chlorpyrifos

Decreased DNA and protein synthesis across the cerebellum, brainstem and forebrain

Subjects: Unspecified strain rats

Chemical: Chlorpyrifos

Low doses tested: 2.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – single dose (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 21)

Age of measurement: post-natal day 1

Reference [PubMed Link]
Whitney KD, Seidler FJ, Slotkin TA. 1995. Developmental neurotoxicity of chlorpyrifos: Cellular mechanisms. Toxicology & Applied Pharmacology 134(1):53-62.
Study Results Study Details References

Results for Chlorpyrifos

Decreased DNA and protein synthesis across the cerebellum, brainstem and forebrain

Subjects: Unspecified strain rats

Chemical: Chlorpyrifos

Low doses tested: 2.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – single dose (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 21)

Age of measurement: post-natal day 1

Reference [PubMed Link]
Whitney KD, Seidler FJ, Slotkin TA. 1995. Developmental neurotoxicity of chlorpyrifos: Cellular mechanisms. Toxicology & Applied Pharmacology 134(1):53-62.
Study Results Study Details References

Results for Chlorpyrifos

Decreased ChE specific activity in the whole brain at all dose levels

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0, or 1.0 and 2.0, or 1.5 and 3.5 mg/kg bw/d

Route of administration: Dissolved in corn-oil and given by gavage

Exposure duration: post-natal day 1 – post-natal day 8 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 29)

Age of measurement: post-natal day 4 and 8

Reference [PubMed Link]
Guo-Ross SX, Chambers JE, Meek EC, Carr RL. 2007. Altered muscarinic acetylcholine receptor subtype binding in neonatal rat brain following exposure to chlorpyrifos or methyl parathion. Toxicol Sci 100(1):118-127.
Study Results Study Details References

Results for Chlorpyrifos

Increased number of working memory errors in males during the first eight visits of the radial maze test; decreased number of reference memory errors in females while increased in males

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1 mg/kg bw/d increasing to 4 mg/kg bw/d

Route of administration: dissolved in corn oil and given by oral gavage

Exposure duration: post-natal day 1 – post-natal day 20 (comparable to human prenatal development from approximately day 1 of week 20 to beyond birth)

Age of measurement: during adolescence

Reference [PubMed Link]
Johnson FO, Chambers JE, Nail CA, Givaruangsawat S, Carr RL. 2009. Developmental Chlorpyrifos and Methyl Parathion Exposure Alters Radial-Arm Maze Performance in Juvenile and Adult Rats. Toxicol Sci 109(1):132-142.
Study Results Study Details References

Results for Chlorpyrifos

Decreased ChE activity in the hippocampus on post-natal day 20

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1 mg/kg bw/d

Route of administration: dissolved in corn oil and given by oral gavage

Exposure duration: post-natal day 1 – post-natal day 20 (comparable to human prenatal development from approximately day 1 of week 20 to beyond birth)

Age of measurement: during adolescence

Reference [PubMed Link]
Johnson FO, Chambers JE, Nail CA, Givaruangsawat S, Carr RL. 2009. Developmental Chlorpyrifos and Methyl Parathion Exposure Alters Radial-Arm Maze Performance in Juvenile and Adult Rats. Toxicol Sci 109(1):132-142.
Study Results Study Details References

Results for Chlorpyrifos

Decreased ChE activity in the hippocampus from post-natal day 20 until post-natal day 40

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1 mg/kg bw/d increasing to 4 mg/kg bw/d

Route of administration: dissolved in corn oil and given by oral gavage

Exposure duration: post-natal day 1 – post-natal day 20 (comparable to human prenatal development from approximately day 1 of week 20 to beyond birth)

Age of measurement: during adolescence

Reference [PubMed Link]
Johnson FO, Chambers JE, Nail CA, Givaruangsawat S, Carr RL. 2009. Developmental Chlorpyrifos and Methyl Parathion Exposure Alters Radial-Arm Maze Performance in Juvenile and Adult Rats. Toxicol Sci 109(1):132-142.
Study Results Study Details References

Results for Chlorpyrifos

In the medium dose regimen: decreased levels of total muscarinic receptor subtypes in the anterior forebrain on post-natal day 8. In the high dose regimen: decreased levels of total muscarinic receptor subtypes in the anterior forebrain; decreased levels of M2/M4, M1ACh and M3ACh receptors in the anterior forebrain; decreased levels of total muscarinic receptors in the posterior forebrain; decreased levels of the M3ACh receptor subtype in the posterior forebrain on post-natal day 8

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0, or 1.0 and 2.0, or 1.5 and 3.5 mg/kg bw/d

Route of administration: Dissolved in corn-oil and given by gavage

Exposure duration: post-natal day 1 – post-natal day 8 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 29)

Age of measurement: post-natal day 4 and 8

Reference [PubMed Link]
Guo-Ross SX, Chambers JE, Meek EC, Carr RL. 2007. Altered muscarinic acetylcholine receptor subtype binding in neonatal rat brain following exposure to chlorpyrifos or methyl parathion. Toxicol Sci 100(1):118-127.
Study Results Study Details References

Results for Chlorpyrifos

Decreased levels of M2/M4 and M3 receptor subtypes and of total muscarinic receptors in the brainstem on post-natal day 8 at all three dose levels. In the high dose regimen: decreased levels of M1 receptor subtype in the brainstem on post-natal day 8; decreased levels of M3 subtype receptor in the brainstem on post-natal day 4

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0, or 1.0 and 2.0, or 1.5 and 3.5 mg/kg bw/d

Route of administration: Dissolved in corn-oil and given by gavage

Exposure duration: post-natal day 1 – post-natal day 8 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 29)

Age of measurement: post-natal day 4 and 8

Reference [PubMed Link]
Guo-Ross SX, Chambers JE, Meek EC, Carr RL. 2007. Altered muscarinic acetylcholine receptor subtype binding in neonatal rat brain following exposure to chlorpyrifos or methyl parathion. Toxicol Sci 100(1):118-127.
Study Results Study Details References

Results for Chlorpyrifos

Gene effects on neurotrophic factors and their signaling pathways.

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5

Reference [PubMed Link]
Slotkin TA, Seidler FJ, Fumagalli F. 2008. Targeting of neurotrophic factors, their receptors, and signaling pathways in the developmental neurotoxicity of organophosphates in vivo and in vitro. Brain Res Bull 76(4):424-38.
Study Results Study Details References

Results for Chlorpyrifos

Gene effects on neurotrophic factors and their signaling pathways.

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5

Reference [PubMed Link]
Slotkin TA, Seidler FJ, Fumagalli F. 2008. Targeting of neurotrophic factors, their receptors, and signaling pathways in the developmental neurotoxicity of organophosphates in vivo and in vitro. Brain Res Bull 76(4):424-38.
Study Results Study Details References

Results for Chlorpyrifos

Major transcriptional changes in genes involved in development of glia and myelin, transcriptional factors involved in cell differentiation, cAMP-related cell signaling, apoptosis, oxidative stress, excitotoxicity and development of neurotransmitter synthesis, storage and receptors for acetylcholine, serotonin, norepinephrine and dopamine.

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5

Reference [PubMed Link]
Slotkin TA, Seidler FJ. 2007. Comparative developmental neurotoxicity of organophosphates in vivo: Transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems. Brain Res Bull 72(4-6):232-274.
Study Results Study Details References

Results for Chlorpyrifos

Major transcriptional changes in genes involved in neural cell growth, development of glia and myelin, transcriptional factors involved in cell differentiation, cAMP-related cell signaling, apoptosis, oxidative stress, excitotoxicity and development of neurotransmitter synthesis, storage and receptors for acetylcholine, serotonin, norepinephrine and dopamine.

Subjects: Sprague-Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5

Reference [PubMed Link]
Slotkin TA, Seidler FJ. 2007. Comparative developmental neurotoxicity of organophosphates in vivo: Transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems. Brain Res Bull 72(4-6):232-274.
Study Results Study Details References

Results for Chlorpyrifos

Alterations in both cell cycle and apoptosis related genes with decreases in 11% and increases in 9% of cell cycle related genes and decreases in 12% and increases in 10% of apoptosis related genes.

Subjects: Sprague Dawley rats

Chemical: Chlorpyrifos

Low doses tested: 1.0 mg/kg bw/d

Route of administration: dissolved in DMSO and injected subcutaneously

Exposure duration: post-natal day 1 – post-natal day 4 (comparable to human prenatal development from approximately day 1 of week 20 to day 1 of week 25)

Age of measurement: post-natal day 5

Reference [PubMed Link]
Slotkin TA, Seidler FJ. 2012. Developmental neurotoxicity of organophosphates targets cell cycle and apoptosis, revealed by transcriptional profiles in vivo and in vitro. Neurotoxicol Teratol 34(2):232-241.