## 2 Environmental and Human Health Impacts of Short-Chain Chlorinated Paraffins
Data on SCCP occurrence in biota show high concentrations in aquatic and terrestrial organisms collected not only from contaminated areas but also from areas with lower anthropogenic activities. The lipid content constitutes the primary determinant of the physical burden imposed by SCCPs on tissues and organs, followed by carbon chain length and degree of chlorination. The bioaccumulation potential of SCCPs in biota has been shown by numerous studies, indicating that it depends on the chlorine content and the carbon chain length [42]. The biomagnification and biodilution of SCCPs have been observed in diverse aquatic and terrestrial food webs, influenced by factors such as food web structure, organism size, feeding habits, biotransformation, outlier treatment, and environmental conditions (e.g., water temperature, dissolved organic matter, and suspended particles). Although the occurrence of SCCPs in the environment has been well documented, substantial knowledge gaps persist regarding their toxicity and the precise molecular mechanisms by which they exert their harmful effects [11]. Experimental animal models and in vitro studies indicate significant acute and chronic toxicity to diverse organisms (including mammals, amphibians, birds, and aquatic organisms). One significant challenge in understanding SCCP toxicity is the broad range of cellular targets these compounds can affect. SCCPs can interfere with multiple biological processes causing oxidative stress and DNA damage; altering energy metabolism and cellular homeostasis; disrupting cellular signaling pathways; and interfering with the endocrine system by activating or inhibiting hormone receptors [60]. Detrimental health consequences include hepatic and renal damage, endocrine disruption, developmental abnormalities, damage to or impairment of the nervous system, immunotoxicity, and reproductive toxicity. Therefore, multiple effects can be caused by exposure to SCCPs, depending on sex and life stage. For example, when zebrafish were continuously administered SCCPs via gavage for three weeks, offspring from the lowest exposure group displayed a marked suppression of immune development, malformation of motor neuronal cell development, and thickened blood vessels [61]. Female zebrafish exposed experienced more severe developmental impairments than the offspring of male-exposed fish. Additionally, RNA sequencing analysis of the liver, muscle, and testes from adult zebrafish revealed potential long-term effects, including increased liver cancer risk, neurotoxicity, and reduced sperm quality. Studies employing human cell culture models have linked SCCP exposure to endocrine disruption, liver toxicity, developmental toxicity, neurotoxicity, and immunotoxicity [11; 57; 60; 62]. A growing body of research indicates additional effects. For example, theotoxic potential of CPs, including SSCPs, through the induction of apoptosis and oxidative stress in cochlear hair cells was investigated recently [63]. The results show that DNA damage and stimulated reactive oxygen species overproduction and endoplasmic reticulum stress were induced, indicating that CPs may pose a risk of ototoxicity at environmentally relevant exposure levels. Notably, SCCPs (C12-CPs, 60% Cl) have been classified as potential human carcinogens by the International Agency for Research on Cancer [57]. There is a significant dearth of population-based studies to comprehensively assess the adverse human health effects associated with SCCP exposure. Population-based studies performed so far have provided evidence suggesting that liver and kidney damage, as well as hematological disorders, such as anemia, may be induced [57]. A recent population-based case-control study involving participants from East China revealed that higher levels of SCCPs were associated with increased type 2 diabetes risk, particularly for male participants and obese individuals. The disruption of lipid metabolism expressed as higher levels of total cholesterol, low-density lipoprotein-cholesterol, and triglycerides were observed [64].