The red fox (Vulpes vulpes, Linnaeus, 1758) is the medium-size canid with the widest world distribution [1]. This species is present throughout the northern hemisphere and regions of North Africa and has been introduced into Australia, where it is considered a plague [1,2]. It is listed as least concern by the International Union Conservation of Nature (IUCN), and in some countries is hunted by its fur and meat [1]. It is highly adaptable to local environmental conditions so that this animal can be found in urban, suburban, and rural areas. Red foxes live in small family groups and are more active at night [2]. They are opportunist predators who can adjust their diet to seasonal and local availability. Their heterogeneous diet can include fruits, invertebrates, small mammals, birds, and even rubbish [2,3]. Their main predators are large carnivores (e.g., wolves, bears), large birds of prey (e.g., golden eagles), and humans [2,4]. The major cause of the admission of these animals to wildlife rehabilitation centers is traffic accidents and poisoning [5,6]. Foxes also harbor a number of pathogens, including some zoonotic [2].

Because the red fox is one of the most widely distributed wild mammals, feeds on a broad range of food resources, and lives in close contact with humans, it has been proposed as a sentinel species in several studies (Figure 1). A sentinel species is used to detect and monitor the presence and effects of contaminants in the animals introduced or living in their habitat [3,7,8]. It also allows the identification of threats, namely infectious agents (e.g., viruses, bacteria), or other anthropogenic hazards, that represent a risk to the fauna and flora of the ecosystem and potentially to humans [9].

A sentinel species, in a One Health context, can give us the tools to predict environmental changes and disease outbreaks. As a result, early actions could be taken to prevent catastrophic consequences, as we saw in the case of the COVID-19 pandemic. Thus, the aim of this work is to compile the studies that use the red fox (V. vulpes) as a sentinel species.

To produce this review, we conducted a literature search through the main web search engines, which included Google Web, Google Scholar, Web of Knowledge, Re-search Gate, and PubMed, as well as in the more relevant ecological ecology, chemistry, veterinary, and similar themed journals. To collect articles related to red fox (V. vulpes) as environmental sentinel bioindicators, our search terms included combinations of fox, red fox, Vulpes vulpes, bioindicator, environmental sentinel, one health, pollution, toxics, antimicrobial resistance, environmental contaminants, heavy metals, disease, poison, morbidity, mortality, persistent organic pollutants, zoonosis, infectious diseases, parasites, organochlorides. As inclusion criteria, only works that describe information regarding Vulpes vulpes as environmental sentinels were included.

Overall, we analyzed a total of 112 research works published between the years 1963 to 2021. To facilitate the description of the studies, they were grouped under an integrated “One Health” vision, taking into consideration the main threats to environmental, human, and animal health.

Organochlorine pesticides, polychlorinated biphenyls (PCBs), polybrominated di-phenyl ethers (PBDEs), and heavy metals are ubiquitous environmental contaminants that originated from human activities, such as agriculture, burning of fossil fuels, industrial activities, and transportation [3,10,11]. They are toxic and have the potential to persist in ecosystems. Due to high lipophilia, they can accumulate in the adipose tissues of vertebrates and bio magnify in food chains [10].

Foxes are significant elements in the food chain [12]. Carnivores, such as foxes, tend to have higher levels of polluting residues than herbivorous animals as a result of bioaccumulation effects between trophic levels. It is, therefore, necessary to trace the presence and the number of chemical substances, such as heavy metals and pesticides, in their tissues. Contaminants studies make it possible to understand the organic changes in the animal, but also the potential dangers for human health [13,14]. Contaminants’ exposition, during long times and at low doses, can alter physiological processes (e.g., metabolism, hormonal changes), decrease animal body condition (e.g., small and weak animals), immunotoxic effects, decrease reproductive success (e.g., infertility, abortion, malformations), and can result in genotoxic and mutagenic effects (cancer) [8,15,16].

Table 1 presents the published works associated with environmental contaminants studies in V. vulpes. The majority of the studies (out of 35) were conducted in Europe (n = 34), with the largest number in Poland (n = 12) and Italy (n = 7). The research focused on wild foxes, with the exception of two cases where red foxes were raised on farms for fur [17].

Substance	Number of Animals	Origin Animal	Sample	Country	Year	Reference
Cr, Cu, Ni, Pb, Zn	20	Wild and Fur farm	Hair and skin	Poland	2011	[17]
Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn	48	Wild	Small intestines	Czech Republic	2010–2011	[34]
Cd, Pb, Cu, Zn	87	Wild	Kidney and liver	Switzerland	1997–1998	[35]
Pb, Cd, Hg	30	Fur Farm	Kidney	Poland	2008	[36]
Cu, Ni, Zn, Co, Cd, Pb	10	Wild	Kidney	Hungary	2008	[37]
Hg	37	Fur farm	Hair and skin	Poland	2014	[17]
Hg, Pb, Cd, Cr, As	18	Wild	Liver, kidneys, and muscles	Slovak Republic	1998–1999	[12]
Cd, Pb, Zn	250	Wild	Kidney	Spain	2003–2011	[38]
Cd, Pb, Zn.	36	Wild	Kidney, liver and muscle	Poland	2002–2003	[39]
Hg	6	Wild	Liver and kidney	Russia	2007–2011	[14]
Al, Ca, Cr, Cu, Fe, Mg, Mn, Ni, Pb	56	Wild	Liver	Romania	May–September 2014	[40]
Hg	200	Wild	Liver, muscle, kidney, hair, bone	Alaska	2010–2011	[28]
Zn, Cu, Pb, Cd, Hg	30	Wild	Cartilage, compact bone, and spongy bone	Poland	2008–2009	[41]
Pb, Cu	42	Wild	Muscle and skin	Italy	2010	[13]
Cd, Pb, Cr, Cu, Zn, Mn, Ni	27	Wild	Intestine	Czech Republic	2009 to 2010	[42]
Hg	27	Wild	Liver, muscle, and kidney	Poland	2004–2006	[29]
Mn, Fe, Sr	38	Wild	Bone	Poland	2008–2009	[43]
Hg, Cd, Pb	46	Wild	Liver	Italy	1992	[30]
As, Cd, Cu, Pb, Hg	28	Wild	Liver, kidney and muscle	Croatia	2008–2009	[44]
Pb, Cd, Cr, Hg	Unknown	Wild	Heart, liver, diaphragm, kidney, muscle, and adipose tissue	Italy	1994–1995	[10]
PCB, DDE	Unknown	Wild	Heart, liver, diaphragm, kidney, muscle, and adipose tissue	Italy	1994–1995	[10]
PCB, Dieldrin, DDT, Endosulfan, HCB, Heptachlor	192	Wild	Perirenal adipose tissue, Kidney	Switzerland	1999–2000	[25]
PCB	80	Wild	Muscle	Germany	1983–1991.	[24]
PCBs, DDT	23	Wild	Adipose tissue	Italy	1991–1992	[3]
HCB, DDT, PBC	57	Wild	Muscle and adipose tissue	Italy	1992–1993	[3]
PBDEs	33	Wild	Adipose tissue, liver, and muscle	Belgium	2003–2004	[45]
HCB, DDT, PCB	36	Wild	Adipose tissues and muscle	Italy	1992	[30]
PCB	20	Wild	Liver, lungs	Poland	2008–2009	[26]
Aldrin, cis-chlordane, trans-chlordane, DDE, DDD, DDT, dieldrin, endosulfan, endrin, HCB, heptachlor, heptachlor-exo-epoxide, iso-drin, methoxychlor, mirex, PBC	18	Wild	Plasma, liver, and adipose tissue	Spain	2004–2006	[46]
Fluoride	32	Wild	Bone	Poland	2014	[32]
Fluoride	34	Wild	Teeth	Poland	Unknown	[31]
Fluoride	182	Wild	Mandible	Great Britain	Unknown	[31]
Fluoride	35	Wild	Teeth	Poland	2004/2005 and 2005/2006	[7]
90Sr, 238,239+240Pu, 241Am and 137Cs	183	Wild	Jaw bones	Poland	2008	[33]

With respect to the type of contaminant, 20 studies were performed on heavy metals, 14 on pesticides/PCBs/PBDEs, and one on radioactive compounds.

Research works on pesticides using the fox as a sentinel are more common for the Arctic fox than the red fox [18,19,20,21,22]. Acute toxicity probably appears to be more common in these animals than the non-lethal chronic effects of pesticides [2]. Indeed, accidental or deliberate poisoning by organochlorine pesticides, biocides, and rodenticides is one of the main causes of red fox admission to wildlife rehabilitation centers [23]. Contrary to expectations, since these animals live near farms and agricultural fields, the pesticides levels in red foxes’ tissues seem to be low, and probably are not associated with adverse health effects. In a study performed in Germany, the investigation of samples from 1983, 1987, and 1991 showed a reduction in the levels of the highly chlorinated biphenyls 138, 153, and 180 [24]. A similar study conducted in Zurich showed a general reduction in exposure to PCBs, with lower levels of PCBs in samples obtained from 1999 to 2000 [25]. In Poland, the ΣPCBs (sum of PCBs: 28, 52, 101, 118, 138, 153, 180) levels in the liver and lungs were 389.99 ng/g and 110.57 ng/g of lipid weight [26]. In Italy, the investigators found in muscle concentrations of 20.2 µg g µ1 lipid in muscle and 7.2 µg g µ1 lb in adipose tissue [27]. While the levels were found to be low, ongoing studies are important for monitoring pesticides environmental pollution.

Several studies have been carried out to determine heavy metal concentrations (Cd, Cr, Cu, Fe, Mn, Ni, Pb, Zn) in red foxes. Mercury (Hg) is one of the most studied and presents variations according to the geographic location of the animals. Wild foxes living near water sources have naturally higher levels of mercury in their tissues, possibly as a result of feeding higher up the food chain [28]. Studies in Slovakia [14], Russia [14], Poland [29], and Spain [30] have shown toxic levels of mercury in red fox fever, which appear to increase with age. Wild foxes have elevated levels of mercury in their tissues, even in populations living in isolated areas as Alaska [28].

Fluoride (F−) pollution has been increasing over the last several decades. In excess, fluoride can cause toxic effects on living organisms, such as dental and bone fluorosis and bone tumors [7]. In Poland, two different studies detected concentrations from 176 to 3668 mg/kg dw in bone [7,31] and 230 and 296 mg/kg dw in mandibular first molars. The interpretation of these values reflects moderate fluoride contamination in the area and makes red foxes a promising sentinel to access industrial pollution [7,31,32].

The study of radioactivity was carried out in the Ukraine, where the Chernobyl nuclear accident occurred. Fox bones did not show a high level of contamination in comparison to the results obtained on the bones of small animals (rodents or insectivorous mammals) previously determined. This suggests that there is no accumulation of bone isotopes at the top of the food chain [33].