Table 5.

Evidence from experimental and human studies, on mode(s) of action and main long term effects from chronic/repeated exposure to E-waste chemicals. Available safe dose (total daily, or weekly, dietary intake or upper level) are reported

Chemical	Mode(s) of action	Effects	Reference dose
PCDD/Fs	Significant bioaccumulation related to lipid solubility. Interaction with the AhR.	Reproductive and neurobehavioral development Immune development Carcinogenicity	TWI: 14 pg WHO-TEQ/kgbw
PBDEs	Significant bioaccumulation related to lipid solubility. Interaction with thyroid hormones. BFR may activate Pathways related to nuclear receptors, as shown by the Expression of the CYP isoforms CYP1A1, CYP2B and CYP3A, representing of, respectively. Aryl-Hydrocarbon (AhR, dioxin receptor), Constitutive-Androstane and Pregnane-X receptors	Reproductive development Neurobehavioral development Thyroid function, Hormonal effect levels in animals start from ca 1 mg/kgbw, but effects on spermatogenesis, suggesting hormonal causes have been observed at a low dose (60 μg/kgbw) of the PBDEs congener BDE-99	TDI: 0.15 μg/kgbw
PCBs	Significant bioaccumulation related to lipid solubility. Congeners with different modes of action: DL PCBs are similar to PCDD/Fs (interaction with AhR), though generally less potent; NDL PCBs show different properties concerning toxicity and persistence: interference with the metabolism of thyroid and estrogens, oxidative stress	Both NDL and DL PCBs may exert a variety of toxicological effects, including carcinogenicity on multiple targets such as liver, thyroid, immune function, reproduction and neurobehavioral development. DL PCB may act as tumor promoters in tissues such as liver; different congeners may alter different pathways, such as the induction of oxidative stress and/or inhibition of apoptosis	TWI (DL PCB): 14 pg WHO-TEQ/kgbw
PAHs (high molecular weight)	Genotoxic damage Oxidative stress Interaction with AhR	Carcinogenicity Mutagenicity Teratogenicity
Al	Interaction with Ca cell-cell communication	Skeletal development and metabolism, Neurotoxicity Foetal toxicity	TWI: 1 mg/kgbw
As	Oxidative stress Interaction with glucorticoid receptor	Skin alterations. Decreased nerve conduction Increased risk of diabetes and cancer (skin and other tissues)
Cd	Oxidative stress Interaction with essential elements as Ca and Se Agonist of ERα	Kidney damage, renal toxicity, bone disease (osteomalacia and osteoporosis). Possibly reproductive damage, and lung emphysema.	0.14–0.26 mg per day
Cu	Essential elementa, may be toxic at high dose levels	Liver damage	upper level: 5 mg per day
Cr(VI)	Cytotoxicity Oxidative DNA damage, mRNA expression of StAR, SF-1, 17β-HSD-1, 17β-HSD-2, FSHR, LHR ERα and ERβ Hypothalamic-pituitary-gonadal axis Oxidative stress	Carcinogenicity Reproductive functions Endocrine function Ovotoxicity
Fe	Essential elementa, may be toxic at high dose levels	Liver damage	not established
Hg	Interaction with sulphur aminoacids Cell proliferation/differentiation/communication Interaction with Se, Methylmercury can bioaccumulate	Neurobehavioral development of children (especially methymercury) Anemia, kidney damage, chronic neurotoxicity
Pb	Interaction with sulphur aminoacids Cell proliferation/differentiation/communication	Neurobehavioral development of children Anemia, kidney damage, chronic neurotoxicity
Se	Essential elementa, may be toxic at supranormal dose levels. Interaction with sulphur aminoacids	Hair loss, Nail brittleness, cardiovascular, renal and neurological abnormalities	300 μg per day
Zn	Essential elementa, may be toxic at high dose levels. Impaired Cu metabolism	Increased risk of Cu deficiency (anemia, neurological abnormalities)	upper level: 25 mg per day

^aEssentiality or toxicity of chemical elements depends on chemical form, oxidation state and solubility

Source: Frazzoli et al. [142]