**2.1 Association between ECSs exposure with LD**

Studies have found that several widespread environmental contaminants can damage the children's developing brains and nervous systems. In our literature review, lead, methylmercury, pesticides, tobacco (cotinine), persistent organic pollutants such as polychlorinated biphenyls (PCBs), and environmental hormones such as bisphenol A and phthalates have been indicated association between neuronal disability and exposure levels in children (Table 3). For instances, prenatal tobacco and childhood lead exposures may be significant risk factors for ADHD, especially when individuals are exposed to both of these toxicants (Froehlich et al. 2009). Although the U.S. has made considerable strides in reducing these toxicant exposure, 15% of women reported smoking during pregnancy in the U.S. population-based study in 2004 (Allen et al. 2008), and an estimated 1.6% of U.S. children showed blood lead levels of concern (≥10 µg/dL) in 1999–2002, with almost 14% having levels of 5 to 9 µg/dL (CDC 2005). These findings suggest that reduction of toxicant exposure may be an important role for the preventions of ADHD as well as other neurodevelopmental disorders in children.

In addition, the accumulating evidences suggest a link between lead exposure and memory impairment. van Wijngaarden *et al.* (2009) conducted a pilot study of 47 healthy subjects aged 55-67 years to examine associations between bone lead levels and 4 tests sensitive to the natural history of Mild Cognitive Impairment (MCI) and Alzheimer's disease (AD), which included 3 subtests of the Cambridge Neuropsychological Test Automated Battery (delayed match-to-sample, paired associates learning and spatial recognition memory) and

Environmental Chemical Substances

(Chen et al. 1992; Chen et al. 1994).

Arsenic

Arsenic

Cobalt

Copper

Copper

Copper

Copper, mercury

in Relation to Neurodevelopmental Disorders: A Systematic Literature Review 319

effects of PCBs on children's neurological development. It should be noted that adverse effects on intelligence and behavior have been found in girls who were highly exposed to mixtures of PCBs, chlorinated dibenzofurans, and other pollutants prior to conception

Morton and Caron 1989

Schrauzer et al. 1992

Rimland and Larson 1983

Guilarte and Chen 2007

Gronlund et al. 2006

Bellinger et al. 1987; Bellinger et al. 1991;

Benetou-Marantidou et al. 1988; Fergusson et al. 1997; Jusko et al. 2008; McMichael et al. 1988; Mendelsohn et al. 1998; Rabinowitz et al. 1992; Stokes et al. 1998; (Schwartz et al. 2000; Ris et al. 2004; Shih et al. 2006; Schwartz et al. 2007; van Wijngaarden et al. 2009 ; Mahmoudian et

very low lead exposure Minder et al. 1998; Surkan et al. 2007

al. 2009

Bolla-Wilson and Bleecker 1987

**Chemicals Study type/hazard effects References** 

learning disabled children Pihl and Parkes 1977

Encephalopathy: an

Neuropsychological impairment following inorganic arsenic exposure

Cobalt Hair element content in

studies

disease

Lead Cognition in children and

Lead Preschool children

implications

uncommon manifestation of workplace arsenic poisoning?

Evidence for interactions of lithium with vitamin B12 and with other trace elements

Hair mineral analysis and behavior: an analysis of 51

Manganese inhibits NMDA receptor channel function:

Poor cognitive development and abdominal pain: Wilson's

Copper, Zinc Brain and behavior Pfeiffer and Braverman 1982

Lead, arsenic Two metals, ADHD Calderon et al. 2001 Lead The Edinburgh Lead Study Thomson et al. 1989

School children Capel et al. 1981

Lead, smoke verbal memory, ADHD Bleecker et al. 2005; Braun et al. 2006

Copper Dose-effect relationships Bowler et al. 2007

the Montreal Cognitive Assessment Test. By measurements of bone lead concentrations, higher tibial and calcaneal bone lead values were significantly (p<0.05) associated with lower performance levels on delayed match-to-sample and paired associates learning in unadjusted analyses with Spearman rank correlation coefficients of about 0.4. Multiple linear regression analyses (i.e., least-squares means of cognitive test scores across tertiles of lead exposure) adjusted for age, education and smoking status continued to show an association of higher calcaneal lead levels with increasing memory impairments on delayed match-to-sample (p=0.07). As might be expected, additional adjustment for history of hypertension reduced the strength of this association (p=0.19). Given the demonstrated impact of lead exposure on hypertension and the vascular aetiology of certain dementias, authors speculated that hypertension could play a mediating role in the association between lead exposure and memory impairment.

Pesticides and their degradation products are ubiquitous in the environment. The most commonly detected indoor pesticides (organophosphates and pyrethroids), which are routinely applied in classrooms and playgrounds, are well-known neurotoxicants that affect the ability to learn and process information (Tulve et al. 2006). In our literature survey, Xu *et al.* (2011) examined the association between body burden of trichlorophenol (TCP) (ie, 2,4,5- TCP and 2,4,6-TCP) and ADHD by logistic regression analyses using data from the 1999– 2004 National Health and Nutrition Examination Survey (NHANES) to evaluate the association between urinary TCPs and parent-reported ADHD among 2546 children aged 6– 15 years. Their results showed that children with low levels (<3.58 μg/g) and high levels (≥3.58 μg/g) of urinary 2,4,6-TCP had a higher risk of parent-reported ADHD compared to children with levels below the limit of detection (OR 1.54, 95% CI 0.97 to 2.43 and OR 1.77, 95% CI 1.18 to 2.66, respectively; p for trend=0.006) after adjusting for covariates. No association was found between urinary 2,4,5-TCP and parent-reported ADHD. These results suggested that exposure to TCP may increase the risk of behavioural impairment in children, especially in countries where organochlorine pesticides are still commonly used. It also should be noted that Rauh *et al.* (2006) reported the impact of prenatal exposure to chlorpyrifos on 3-year neurodevelopment and behavior in city-residential minority 254 children. The report examined cognitive and motor development with the Bayley Scales of Infant Development II and child behavior with the Child Behavior Checklist and chlorpyrifos levels in umbilical cord plasma. Highly exposed children (chlorpyrifos levels of >6.17 pg/g plasma) scored, on average, 6.5 points lower on the Bayley Psychomotor Development Index and 3.3 points lower on the Bayley Mental Development Index at 3 years of age compared with those with lower levels of exposure. Children exposed to higher in compared with lower chlorpyrifos levels were also significantly more likely to experience Psychomotor Development Index and Mental Development Index delays, which are attention problems, ADHD problems, and pervasive developmental disorder problems at 3 years of age. The proportion of delayed children in the high-exposure group, compared with the low-exposure group, was 5 times greater for the Psychomotor Development Index and 2.4 times greater for the Mental Development Index.

It was also reported that children prenatally exposed to PCBs might be related with lowered intelligence and behavioral deficits. Relationships between adverse health effects and PCB exposure during infancy and childhood have been examined. Although some inconsistencies in the literature exist, the overall evidence supports a concern for adverse

the Montreal Cognitive Assessment Test. By measurements of bone lead concentrations, higher tibial and calcaneal bone lead values were significantly (p<0.05) associated with lower performance levels on delayed match-to-sample and paired associates learning in unadjusted analyses with Spearman rank correlation coefficients of about 0.4. Multiple linear regression analyses (i.e., least-squares means of cognitive test scores across tertiles of lead exposure) adjusted for age, education and smoking status continued to show an association of higher calcaneal lead levels with increasing memory impairments on delayed match-to-sample (p=0.07). As might be expected, additional adjustment for history of hypertension reduced the strength of this association (p=0.19). Given the demonstrated impact of lead exposure on hypertension and the vascular aetiology of certain dementias, authors speculated that hypertension could play a mediating role in the association between

Pesticides and their degradation products are ubiquitous in the environment. The most commonly detected indoor pesticides (organophosphates and pyrethroids), which are routinely applied in classrooms and playgrounds, are well-known neurotoxicants that affect the ability to learn and process information (Tulve et al. 2006). In our literature survey, Xu *et al.* (2011) examined the association between body burden of trichlorophenol (TCP) (ie, 2,4,5- TCP and 2,4,6-TCP) and ADHD by logistic regression analyses using data from the 1999– 2004 National Health and Nutrition Examination Survey (NHANES) to evaluate the association between urinary TCPs and parent-reported ADHD among 2546 children aged 6– 15 years. Their results showed that children with low levels (<3.58 μg/g) and high levels (≥3.58 μg/g) of urinary 2,4,6-TCP had a higher risk of parent-reported ADHD compared to children with levels below the limit of detection (OR 1.54, 95% CI 0.97 to 2.43 and OR 1.77, 95% CI 1.18 to 2.66, respectively; p for trend=0.006) after adjusting for covariates. No association was found between urinary 2,4,5-TCP and parent-reported ADHD. These results suggested that exposure to TCP may increase the risk of behavioural impairment in children, especially in countries where organochlorine pesticides are still commonly used. It also should be noted that Rauh *et al.* (2006) reported the impact of prenatal exposure to chlorpyrifos on 3-year neurodevelopment and behavior in city-residential minority 254 children. The report examined cognitive and motor development with the Bayley Scales of Infant Development II and child behavior with the Child Behavior Checklist and chlorpyrifos levels in umbilical cord plasma. Highly exposed children (chlorpyrifos levels of >6.17 pg/g plasma) scored, on average, 6.5 points lower on the Bayley Psychomotor Development Index and 3.3 points lower on the Bayley Mental Development Index at 3 years of age compared with those with lower levels of exposure. Children exposed to higher in compared with lower chlorpyrifos levels were also significantly more likely to experience Psychomotor Development Index and Mental Development Index delays, which are attention problems, ADHD problems, and pervasive developmental disorder problems at 3 years of age. The proportion of delayed children in the high-exposure group, compared with the low-exposure group, was 5 times greater for the Psychomotor Development Index and

It was also reported that children prenatally exposed to PCBs might be related with lowered intelligence and behavioral deficits. Relationships between adverse health effects and PCB exposure during infancy and childhood have been examined. Although some inconsistencies in the literature exist, the overall evidence supports a concern for adverse

lead exposure and memory impairment.

2.4 times greater for the Mental Development Index.

effects of PCBs on children's neurological development. It should be noted that adverse effects on intelligence and behavior have been found in girls who were highly exposed to mixtures of PCBs, chlorinated dibenzofurans, and other pollutants prior to conception (Chen et al. 1992; Chen et al. 1994).


Environmental Chemical Substances

DDT Children study

Polyaromatic

Polycyclic aromatic hydrocarbon

Industrial

Industrial

solvents Workers

Polychlorinated

in Relation to Neurodevelopmental Disorders: A Systematic Literature Review 321

Dioxin Children study van den Hazel et al. 2006; Lee et al. 2007

PCBs Children study Chen et al. 1992; Chen et al. 1994; Roegge

biphenyl Children study Sandberg et al. 2003; Lin et al. 2008

Phenol Children study Gross et al. 1987; Hertz-Picciotto et al.

Table 2. Literature lists for the hazard effects of ECSs on human memory and cognition.

As above mentioned, several ECSs have been related with developmental delay such as ADHD and LD in human studies. However, little is known about the underlying mechanism by which ECSs could induce developmental delay. Animal experiments and *in vitro* studies using cells are useful to elucidate these kinds of mechanisms and understand the results of human studies. Animal studies listed in Table 3 indicate that most attentions have been focused on lead, mercury, pesticides and polycyclic aromatic hydrocarbons (PAHs). For example, toxic properties of lead have been attributed to its capability to mimic calcium and alter calcium homeostasis. One of the reasons for the deleterious effects of lead is its ability to strongly bind to sulfhydryl groups of proteins and to mimic or compete with calcium (Flora et al. 2007). It is known that lead, even at picomolar concentration, competes with calcium for binding sites on cerebellar phosphokinase C, thereby affecting neuronal signaling and neurotransmitter release (Bressler and Goldstein 1991), inhibiting calcium entry into cells (Simons 1993). Lead disrupts mitochondrial calcium homeostasis,

**2.2 Possible mechanism of ECSs-induced autism and developmental delay** 

intercellular oxidants levels, ATP production, and apoptogenic factors.

solvents Children study Uzun and Kendirli 2005a; Dick et al. 2010

al. 2009

Children study Walhovd et al. 2007; Bandstra et al. 2010;

2011

van Elderen et al. 2010

2001; LoSasso et al. 2002

Christenson et al. 2001; Griffin et al. 1993; Aase et al. 2006; Christenson et al. 1991; Dorner and Plagemann 2002; Sharma et

and Schantz 2006; Lin et al. 2010

Hanninen et al. 1976; Ryan et al. 1988; Moen et al. 1990; Morrow et al. 1992; Stollery and Flindt 1988; Bowler et al. 2001; LoSasso et al. 2001; Morrow et al.

**Chemicals Study type/hazard effects References** 

Formaldehyde Children study Madrid et al. 2008 Formaldehyde Workers LoSasso et al. 2001

hydrocarbon Children study Sheng et al. 2010


Fergusson and Horwood 1993; Lyngbye et al. 1990; Tong et al. 1996; Tuthill 1996; Leviton et al. 1993; Minder et al. 1994; Buchanan et al. 1999; al-Saleh et al. 2001; Lanphear et al. 2005; McMichael et al. 1988; Canfield et al. 2003; Chiodo et al. 2007; Counter et al. 2008; Nigg et al. 2008; Schnaas et al. 2006; Wang et al. 2002; Wang et al. 2008; Kim et al. 2010

Grandjean et al. 1997; Schettler 2001; Counter et al. 2005; Johansson et al. 2007; Dufault et al. 2009; Valent et al. 2011

Marshall et al. 1995; Robertson and Jackson 1996 Lassen and Oei 1998; Rowland et al. 2002; Batstra et al. 2003; Najman et al. 2004; O'Brien et al. 2004; Matsumoto et al. 2005; Uzun and Kendirli 2005b; Kukla et al. 2008; Petry et al. 2008; Kargoshaie et al. 2009; Anderko et al. 2010; DeGarmo et al. 2010; Freire et al.

2010; O'Callaghan et al. 2010

Wang et al. 2009b

al. 2011

Ivanovic et al. 2000; Molina and Pelham 2001; Kalyva 2007; Keselyak et al. 2007;

Stephens et al. 1995; Schettler 2001; Kofman et al. 2006; Rauh et al. 2006; Xu et

**Chemicals Study type/hazard effects References** 

chemicals Stewart et al. 2006

Mercury Workers Piikivi and Hanninen 1989; Counter et al.

monoxide Workers Deschamps et al. 2003; Katirci et al. 2011

2005

(ADHD, learning disabilities)

Mercury infant immunizations Redwood et al. 2001

Mercury Adult exposure Yokoo et al. 2003

Molybdenum A case report Momcilovic 1999

magnetic Children study Moss et al. 1997

Cotinine Adult Patients study Smith et al. 2009

Pesticide A case study. Reidy et al. 1994

Pesticide Workers Srivastava et al. 2000

monoxide Children study Binder and Roberts 1980

Children study three

Lead School children

Mercury Children study

Smoking Children study

Pesticide Children study

Smoking Adolescent student study

Lead, mercury,

Phosphorus-31

Carbon

Carbon

PCB


Table 2. Literature lists for the hazard effects of ECSs on human memory and cognition.

#### **2.2 Possible mechanism of ECSs-induced autism and developmental delay**

As above mentioned, several ECSs have been related with developmental delay such as ADHD and LD in human studies. However, little is known about the underlying mechanism by which ECSs could induce developmental delay. Animal experiments and *in vitro* studies using cells are useful to elucidate these kinds of mechanisms and understand the results of human studies. Animal studies listed in Table 3 indicate that most attentions have been focused on lead, mercury, pesticides and polycyclic aromatic hydrocarbons (PAHs). For example, toxic properties of lead have been attributed to its capability to mimic calcium and alter calcium homeostasis. One of the reasons for the deleterious effects of lead is its ability to strongly bind to sulfhydryl groups of proteins and to mimic or compete with calcium (Flora et al. 2007). It is known that lead, even at picomolar concentration, competes with calcium for binding sites on cerebellar phosphokinase C, thereby affecting neuronal signaling and neurotransmitter release (Bressler and Goldstein 1991), inhibiting calcium entry into cells (Simons 1993). Lead disrupts mitochondrial calcium homeostasis, intercellular oxidants levels, ATP production, and apoptogenic factors.

Environmental Chemical Substances

**Species**

Copper mice Indicator in the Alzheimer's

Copper rabbit Indicator in the Alzheimer's

Lead mice Developmental exposure

Lead rats Developmental exposure

Mercury mice Prenatal exposure and

Mercury mice Developmental exposure

Mercury rats Developmental exposure

Mercury rats Dose-dependent study of

Mercury monkey Developmental exposure

Uranium rats Developmental exposure

Carbon monoxide disease model

disease model

**Chemicals Animal** 

in Relation to Neurodevelopmental Disorders: A Systematic Literature Review 323

**References** 

Fisher et al. 1991; Quinn et al. 2010

Woodruff-Pak et al. 2007

2000 Zhang et al. 2002; Garcia-Arenas et al. 2004; Vazquez and Pena de Ortiz 2004; Haider et al.

Kumar and Desiraju 1992; Altmann

Yoshida et al. 2005; Eddins et al.

Sakamoto et al. 2002; Falluel-Morel

Garavan et al. 2000

2005; Flora et al. 2007

et al. 1993; Yang et al. 2003

Montgomery et al. 2008

2008

2007

et al. 2007

Hellberg 1972

Sakamoto et al. 2004

Sanchez et al. 2006

**Models and experimental types** 

Copper mice Mechanistic study Lu et al. 2006; Lu et al. 2009

Copper rabbit Mechanistic study Sparks and Schreurs 2003

Cobalt rats Mechanistic study Nerobkova and Voronina 1988 Lead mice Mechanistic study Gao et al. 2005; Railey et al. 2011

Lead rats Mechanistic study Alkondon et al. 1990; Adhami et al.

Lead rats Behavioral analysis Tang et al. 1994; Fan et al. 2009

Copper rats Mechanistic study Obernier et al. 2002; Begum et al.

2008

Copper hamster Mechanistic study Bareggi et al. 2009

Copper rats Competition with zinc Railey et al. 2010

and behavioral analysis

and behavioral analysis

and behavioral analysis

Mercury rats Mechanistic study Vicente et al. 2004

and behavioral analysis

Developmental exposure

and behavioral analysis

and behavioral analysis

Vanadium mice Behavioral analysis Avila-Costa et al. 2006

Vanadium mice Mechanistic study Han et al. 2008

Vanadium rats Mechanistic study Mao et al. 2008

Uranium rats Behavioral analysis Albina et al. 2005; Houpert et al.

mice Behavioral analysis Meunier et al. 2006

Behavioral analysis

Rats in the benzo(a)pyrene (B(a)P) -treated groups have significantly impaired Morris water maze performance when compared to controls (Chengzhi et al. 2011). The B(a)P-induced neuronal damage was found in the hippocampus under transmission electron microscopy. Their results demonstrated that LM deficits associated protein expression signatures could be identified from tissue proteomes, as well as potential biomarkers such as retinoic acid receptor b (RARb), synaptotagmin iosfomrs 1 (Syt1) and brain-derived neurotrophic factor (BDNF). This finding is the first time that multiple novel proteins that are dysregulated by B(a)P, which both enhance our understanding of B(a)P induced locomotor deficits and represent targets of novel therapeutics. Prenatal morphine can alter the synaptic complex of postsynaptic density 95 with N-methyl-D-aspartate receptor subunit in hippocampal CA1 subregion of rat offspring leading to long-term cognitive deficits (Lin et al. 2009). This morphine model might be useful for understanding mechanisms of long-term cognitive deficit induced by other ECSs such as lead and PCBs.

Originally, organophosphate pesticides (OPs) have been thought to exert their effects on brain development secondarily by their ability to inhibit cholinesterase. However, it became now clear that these agents act as developmental neurotoxicants through a number of differential mechanisms. Some of which operate at exposures below the threshold for cholinesterase inhibition may differ in their effects on brain development and their consequent impacts on behavioral performance (Paul et al. 1994; Cohn and MacPhail 1997; Itoh et al. 1997a, 1997b; Palumbo et al. 2001; Castillo et al. 2002; Levin et al. 2002; Aldridge et al. 2005; Spowart-Manning and van der Staay 2005; Timofeeva, 2008; Verma et al. 2009; Levin et al. 2010). A series of studies with toxico-dynamically equivalent exposures in neonatal rats showed that chlorpyrifos, diazinon and parathion (PRT) elicit behavioral abnormalities in association with adverse effects on acetylcholine (ACh) and serotonin (5HT) circuits, but that the underlying defects and behavioral outcomes differ among the three OPs. In particular, PRT exposure did not elicit the cognitive impairment noted with the other two OPs, as evaluated in the radial-arm maze in adolescence and young adulthood, although, it did share adverse effects on indices of ACh synaptic function.


Rats in the benzo(a)pyrene (B(a)P) -treated groups have significantly impaired Morris water maze performance when compared to controls (Chengzhi et al. 2011). The B(a)P-induced neuronal damage was found in the hippocampus under transmission electron microscopy. Their results demonstrated that LM deficits associated protein expression signatures could be identified from tissue proteomes, as well as potential biomarkers such as retinoic acid receptor b (RARb), synaptotagmin iosfomrs 1 (Syt1) and brain-derived neurotrophic factor (BDNF). This finding is the first time that multiple novel proteins that are dysregulated by B(a)P, which both enhance our understanding of B(a)P induced locomotor deficits and represent targets of novel therapeutics. Prenatal morphine can alter the synaptic complex of postsynaptic density 95 with N-methyl-D-aspartate receptor subunit in hippocampal CA1 subregion of rat offspring leading to long-term cognitive deficits (Lin et al. 2009). This morphine model might be useful for understanding mechanisms of long-term cognitive

Originally, organophosphate pesticides (OPs) have been thought to exert their effects on brain development secondarily by their ability to inhibit cholinesterase. However, it became now clear that these agents act as developmental neurotoxicants through a number of differential mechanisms. Some of which operate at exposures below the threshold for cholinesterase inhibition may differ in their effects on brain development and their consequent impacts on behavioral performance (Paul et al. 1994; Cohn and MacPhail 1997; Itoh et al. 1997a, 1997b; Palumbo et al. 2001; Castillo et al. 2002; Levin et al. 2002; Aldridge et al. 2005; Spowart-Manning and van der Staay 2005; Timofeeva, 2008; Verma et al. 2009; Levin et al. 2010). A series of studies with toxico-dynamically equivalent exposures in neonatal rats showed that chlorpyrifos, diazinon and parathion (PRT) elicit behavioral abnormalities in association with adverse effects on acetylcholine (ACh) and serotonin (5HT) circuits, but that the underlying defects and behavioral outcomes differ among the three OPs. In particular, PRT exposure did not elicit the cognitive impairment noted with the other two OPs, as evaluated in the radial-arm maze in adolescence and young adulthood, although, it did share adverse effects on indices of ACh synaptic function.

> **Models and experimental types**

Arsenic mice Behavioral analysis Miyagawa et al. 2007 Arsenic mice Mechanistic study Martinez-Finley et al. 2009

and behavioral analysis

Aluminum rats Mechanistic study Sethi et al. 2009

deficit model rats

Arsenic rats Mechanistic study Rodriguez et al. 2001

Alzheimer's disease models

mice Mechanistic study Kaneko et al. 2006

**References** 

Rodriguez et al. 2002

Gong et al. 2006

Grossi et al. 2009

deficit induced by other ECSs such as lead and PCBs.

**Chemicals Animal** 

Aluminiummaltolate complex

**Species**

Arsenic rats Developmental exposure

Aluminum rats Aluminum-induced memory

Copper mice Behavioral analysis in


Environmental Chemical Substances

**Species**

PCB rats Developmental exposure

PFOS mice Developmental exposure

**Chemicals Animal** 

Hexachloro-Benzene

Polycyclic aromatic hydrocarbon

Polycyclic aromatic hydrocarbon

Polycyclic aromatic hydrocarbon

Polycyclic aromatic hydrocarbon

Polycyclic aromatic hydrocarbon

Polycyclic aromatic hydrocarbon

in Relation to Neurodevelopmental Disorders: A Systematic Literature Review 325

**References** 

Piedrafita, 2008; Boix, 2010 ; Jolous-

Jamshidi et al. 2010

Johansson et al. 2008

Rueda et al. 2008

Nishio et al. 2001

Benetti, 2009

Kassed, 2002 ; Kim, 2007

1996 Tsutsumi, 2002

Miyagawa et al. 2007

Kawaguchi et al. 2009

Butcher et al. 1972

**Models and experimental types** 

Formaldehyde rats Mechanistic study Aslan, 2006; Liu, 2010

and behavioral analysis

and behavioral analysis

PCB fishes Behavioral analysis Schantz, 2001

mice Behavioral analysis Down syndrome model

rats Developmental exposure and behavioral analysis

Bisphenol mice Developmental exposure

Paraben rats Developmental exposure

Salicylate rats Developmental exposure

experimental animal models.

rats Adult behavioral analysis Revest, 2009

Trimethyltin rats Behavioral analysis Cohn and MacPhail 1996

and behavioral analysis

and behavioral analysis

and behavioral analysis

Bisphenol rats Mechanistic study Poimenova et al. 2010

Trimethyltin mice Mechanistic study Dey et al. 1997; Maurice et al. 1999;

Trimethyltin rats Mechanistic study Oconnell et al. 1994; OConnell et al.

Table 3. Literature lists for effects of environmental chemicals on memory and cognition in

rats Behavioral analysis Valkusz, 2011

mice ADHD model Fredriksson and Archer 2004

rats ADHD model Chengzhi et al. 2011; Lin et al. 2009;

rats Behavioral analysis Sun, 2005; Fedotova and Ordyan

2010

Dioxin rats Mechanistic study Marcus, 2005 Formaldehyde mice Mechanistic study Tong et al. 2011


rats Mechanistic study Thom et al. 2004

rats Behavioral analysis Paul et al. 2003

**References** 

Han et al. 2007; Wang et al. 2009a

Jevtovic-Todorovic et al. 2003; Kumar and Kumar 2009; Comin et

et al. 2007

al. 2010

Richter et al. 2000

Guerrero et al. 1999

Levin et al. 1996

Chen et al. 2010

Sinha et al. 2006

Levin et al. 2010

1994 Itoh et al. 1997a; Itoh et al. 1997b; Palumbo et al. 2001; Castillo et al. 2002; Levin et al. 2002; Aldridge et al. 2005; Spowart-Manning and van der Staay 2005; Timofeeva, 2008; Verma et al. 2009;

et al. 2011

Reddy and Kulkarni 1998; Palumbo

**Models and experimental types** 

rats Mechanistic study and Behavioral analysis

mice Mechanistic study and Behavioral analysis

rats Mechanistic study and Behavioral analysis

hamster Use of precision-cut tissue s Behavioral analysis

Behavioral analysis

Smoking mice Behavioral analysis Paz et al. 2007 Smoking rats Mechanistic study Liang et al. 2006

and behavioral analysis

Pesticide rats Aconitine Mechanistic study Curzon et al. 2006

Pesticide rats Clozapine Levin et al. 2009 Pesticide rats Vinclozolin fungicide Andre, 2006

Pesticide rats DEET Abdel-Rahman, 2004 Dioxin mice Mechanistic study Akahoshi, 2009

Pesticide mice Organophosphates Billauer-Haimovitch et al. 2009; Post

Pesticide rats Organophosphates Cohn and MacPhail 1997; Paul et al.

Pesticide mice Gufosinate-ammonium Calas et al. 2008

Ozone rats Mechanistic study and

Smoking rats Developmental exposure

Pesticide mice quaternary ammonium

Pyrethroid rats Pyrethroid behavioral

herbicide

analysis

**Chemicals Animal** 

Carbon monoxide

Carbon monoxide

Nitrogen oxide

Nitrogen oxide

Nitrogen oxide

NNAL(4 methylnitrosa mino)-1-(3 pyridyl)-1 butanol)

**Species**


Table 3. Literature lists for effects of environmental chemicals on memory and cognition in experimental animal models.

Environmental Chemical Substances

in Relation to Neurodevelopmental Disorders: A Systematic Literature Review 327

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Anderko L, Braun J, Auinger P. 2010. Contribution of tobacco smoke exposure to learning

Andre SM, Markowski VP. 2006. Learning deficits expressed as delayed extinction of a

Aslan H, Songur A, Tunc AT, Ozen OA, Bas O, Yagmurca M, Turgut M, Sarsilmaz M,

Avila-Costa MR, Fortoul TI, Nino-Cabrera G, Colin-Barenque L, Bizarro-Nevares P,

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Batstra L, Hadders-Algra M, Neeleman J. 2003. Effect of antenatal exposure to maternal

Begum AN, Yang F, Teng E, Hu S, Jones MR, Rosario ER, Beech W, Hudspeth B, Ubeda OJ,

Bellinger D, Leviton A, Waternaux C, Needleman H, Rabinowitz M. 1987. Longitudinal

Saudi Arabian schoolgirls. Int J Hyg Environ Health 204(2-3):165-74. Altmann L, Weinsberg F, Sveinsson K, Lilienthal H, Wiegand H, Winneke G. 1993.

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Blockade of Nmda-Activated Channel Currents May Be Implicated in Learning-

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