Table 3.

Neurobehavioral effects of developmental exposures of rodents to OP insecticides.

OP Insecticide	Species/S train	Dose Regimen	Vehicle	Time of Exposure	Starting Testing Age	Behavioral Test	Measured Outcomes (Affected sex)	Reference
Chlorpyrifos	SD Rats	5 mg/kg/day, s.c.	DMSO	GD9-12	PND4	16-arm radial maze	↓ Working and reference memory (M, F)	Icenogle et al., 2004
Chlorpyrifos	ND4 Mice	1 or 5 mg/kg/day, s.c.	DMSO	GD17- 20	PND60	Foraging Maze	↓ Working and reference memory (F > M)	Haviland et al., 2010
Chlorpyrifos	SD Rats	1 mg/kg/day, s.c.	DMSO	GD17-20	Adolescence, Adulthood	· 16-arm radial maze	↓ Working and reference memory (F)	Levin et al., 2002
Chlorpyrifos	SD Rats	1 mg/kg/day, s.c.	DMSO	PND1-4	PND52	16-arm radial maze Elevated + maze Chocolate milk preference test	↓ Working and reference memory (M >F) ↑Anxiety-related behavior (M) Anhedonia (M, F)	Aldridge et al., 2005
Chlorpyrifos	SD Rats	1 mg/kg/day, s.c.	DMSO	PND1-4	PND60	16-arm radial maze	↓ Working and reference memory (M >F)	Levin et al., 2001
Chlorpyrifos	Guinea Pigs	20 mg/kg/day, s.c.	Peanut Oil	GD52-62	PND40	Morris water maze	↓Reference memory (M > F)	Mamczarz et al., 2016
Chlorpyrifos	Guinea Pigs	20 mg/kg/day, s.c.	Peanut Oil	GD52-62	PND40	Morris water maze	↓Learning (only F tested)	Mullins et al., 2015
Chlorpyrifos	C57Bl6/J mice	2.5 or 5.0 mg/kg/day, oral gavage	Corn Oil	GD12-15	PND6-12A PND90B	Reflex scoresA Repetitive novel object contactB Social preference for conspecific and social conditioned preferenceB	↓ Righting, negative geotaxis, cliff avoidance reflexes (only M tested)A,† ↑Object preference (only M tested) B,† ↓Social preference (only M tested) B,†	Lan et al., 2017
Chlorpyrifos	SD Rats	0.3, 1, or 5 mg/kg/day, oral gavage	Corn Oil	GD6-PND10	PND22-24	T-Maze Spatial Delayed Alternation	↔Working memory (M, F)	(Maurissen et al., 2000)
	CD1 Mice	1 or 3 mg/kg/day, s.c.	DMSO	PND1-4 PND11-14	PND35	Stereotypy (grooming, rearing, digging, sniffing) Unrestricted social encounters Preference for novelty	↔Rearing, digging, sniffing ↓Grooming (M, F) ↔Social behavior ↑Novelty preference (M, F)	(Ricceri et al., 2003)
	CD1 Mice	3 mg/kg/day, s.c.	Peanut Oil	PND 11-14	PND1A PND2B PND4C	StereotypyA Light-dark apparatusB Novel objectC	↔Grooming, wall-rearing ↑Digging (F)† ↔Anxiety-like behavior (M > F) ↔Object exploration	(Venerosi et al., 2008)
	CD1 Mice	1 or 3 mg/kg/day, s.c.	Peanut Oil	PND11-14	PND35 PND60 PND90	Open field and Elevated plus maze Stereotypy Maternal response	↑ Anxiety-like behavior (F) ↔Grooming, rearing, digging ↑Maternal response toward M, F	(Ricceri et al., 2006)
	SD Rats	1 mg/kg/day, s.c.A 5 mg/kg/day, s.c.B	DMSO	PND1-4A PND11-14B	PND30	Stereotypy	↔Grooming ↓Rearing (M)A, ↑Rearing (M)B,†	(Dam et al., 2000)
Diazinon	SD Rats	0.5 mg/kg/day, s.c.	DMSO	PND11-14	PND30	Radial arm maze	↓ Working memory (M, F)	Timofeeva et al., 2008a
Diazinon	SD Rats	0.5 or 2 mg/kg/day, s.c.	DMSO	PND1-14	PND52	Elevated plus maze Novelty-suppressed feeding Chocolate milk preference test	↑Anxiety-related behavior (M > F) ↓Time to feeding (M) Anhedonia (M, F)	Roegge et al., 2008
Parathion	SD Rats	0.1 or 0.2 mg/kg/day, s.c.	DMSO	PND1-4	PND30	Radial arm maze	↔WM (M, F)	Timofeeva et al., 2008a
Parathion	SD Rats	0.1 or 0.2 mg/kg/day, s.c.	DMSO	PND 1-4	PND50A PND81B PND112C	Elevated plus mazeA Chocolate milk preference testB Radial arm mazeC	↑Anxiety-related behavior (0.2 mg/kg; M, F) No significant anhedonia ↔ Working memory	Timofeeva et al., 2008b

DMSO, dimethyl sulfoxide; GD, gestation day; ND4 mice are outbred mice descended from the Swiss Webster stock rederived by the University of Notre Dame, Indiana; PND, postnatal day; SD, Sprague-Dawley. The letters M and F in parentheses stand for male and female, respectively. The superscripted capital letters in each row are intended to indicate when a behavioral test was conducted at a specific testing age or when the time of exposure resulted in a specific measured outcome.

^†,indicates behavioral phenotypes observed in rodent models of autism-related disorders.