Saturday, June 17, 2017

[Analysis] How many cats per capita are there?


If you've come to this page, you might be wondering: how many cats per capita are there?

Wednesday, November 9, 2016

[Tutorial] How to access USGS WaterData

If you're interested in learning how to download and digest the USGS water data, feel free to take a look at the video below.

Thanks for watching!

Sunday, August 14, 2016

STELLA: An example of systems thinking and LCA

I've been using the program STELLA for a while now, since at least 2015. Recently, this program has transitioned to STELLA Professional, which is a strong product but costs much more. Nonetheless, STELLA can be a useful program for investigating system behavior.

STELLA is a visually-based system modeling software. It is used heavily in the social sciences, including ecological and environmental sciences. It's especially good for dynamic systems where the relationships between variables is known or well parameterized.

The system contains:

  • stocks (where a material or value can "collect")
  • inflows (which input x amount per timestep where x is their value)
  • outflows (which remove x among per timestep where x is their value)
  • modifiers (which can modify through numerical operation, the function of a inflow or outflow).
There is more, but those are the basics. I have created a set of slides, which will walk you through the process of using STELLA, which I will provide below.

Previously, I have worked on generating a systems diagram of the flow of clay, water and other materials in making ceramic water filters. This was used to calculate greenhouse gas emissions across the lifecycle and the effectiveness of amendments for arsenic removal using ceramic water filters.

Wednesday, April 6, 2016

Some background on fluorine from a final paper

Taming the Savage Beast: Fluorine
Final Paper

A Roman cup carved from fluorspar (Toon, 2011)

Kyle M. Monahan

CEE 167 | Environmental Toxicology

I.                   Introduction

Fluorine is a chemical element with a unique history of human exposure.  The first human use of the naturally occurring element was in the 1500’s as an ore additive, to help the metal mixtures mix together at lower temperatures, and as such called fluores from the Latin flere, meaning “to flow” (Greenwood, 1999). This element is extremely reactive, making it initially hard for scientists to isolate and identify from natural mineral forms such as fluorspar (fluorite). Additionally, the human risks of inhaling the gaseous form of fluorine (hydrofluoric acid; HF) caused injury and even death to investigators attempting to isolate the element (Toon, 2011), leading to long periods of research. The element was noted for an ability to scour glass, demonstrating its corrosive and active nature. As such, when fluorine was finally isolated in 1886 by Henri Moissan, he was awarded the Nobel Prize, stating “the whole world has admired the great experimental skill with which you have studied that savage beast among the elements” (Toon, 2011).

Chemical & Physical Properties
Fluorine is a halogen with the symbol F and an atomic number of nine, and it is the most electronegative element in the periodic table. It is 13th in terrestrial abundance and 24th in universal abundance (Suess and Urey, 1956). It is extremely reactive, and in its free form bonds quickly and readily with other elements. The bond energy of difluorine (F2) is much lower than other halides (Cl2 or Br2) and can easily dissociate, releasing the more reactive F atom (Greenwood and Earnshaw, 1998). Similar to other halides, fluorine in a diatomic gas of pale yellow color at STP, and has a pungent odor (similar to Cl2). Fluorine with combine with all elements except the light noble gases (He, Ne and Ar), and the presence of fluorine in a compound strengthens nearby bonds.

Two examples of these combined elements are sodium fluoride and calcium fluoride (ATSDR, 2003). Sodium fluoride and sodium fluorosilicate are commonly added to drinking water supplies in the United States. Natural compounds containing fluorine include many inorganic minerals (fluorite, fluorapatite, cryolite), but less than a dozen natural organic compounds, mostly derived from Streptomyces and Dichapetalum bacteria metabolism (Dolbier, 2005). Fluorine is found naturally in previously mentioned forms, but fluoride can also be found in synthetically fluorinated organic compounds. For this work, we will use the term “fluoride” to refer to compounds that contain the fluorine atom in their structure; as most scientific instruments detect the sum of all fluorides present in a water sample.

Uses & Manufacture
The chemical properties of fluoride relate to its myriad number of uses across metallurgy, medicine, water treatment, and other fields. The ubiquitous non-stick coating Teflon even contains long carbon chains with fluorine atoms attached. The first recorded uses were as a flux in metal working, but the element and its derivatives are commonly used in medical and scientific applications.  Fluorine is also a necessary ingredient for uranium enrichment, and was used extensively in the Manhattan Project to help build nuclear weapons in the US (Edmunds and Smedley, 2013). About 20% of current pharmaceutical drugs and 30% of agricultural chemicals are man-made organofluorine compounds (Emsley, 2011). A very common drug is the selective serotonin reuptake inhibitor (SSRI) fluoxetine, marketed under the brand name Prozac. Drugs commonly used fluorine-containing compounds to add bond strength to compounds, allowing them to reach areas otherwise impossible, such as fluconazole for fungal treatments in extremities. Fluorine-18 is an isotope that is used in positron emission tomography (PET) due to its short half-life (110 minutes). The 18F isotope is attached to a glucose molecule, injected into the patient, and high resolution images (such as this one) can be produced as the fluorine emits a position as it decays, which collides with an electron and annihilates – releasing gamma radiation, which can be detected and used to image the human body, especially cells heavily using glucose, such as some cancers (Emsley, 2011).

The first noted record of fluoride compounds in water was in the 1930’s when settlers in Arizona and Colorado showed signs of mottled teeth which were linked to groundwater wells containing traces (likely high concentrations due to the high detection limits of the times) of fluorine (Smith, et al 1931). Although high levels of fluorine compounds in water can cause fluorosis, as fluorine compounds replace elements within the enamel structure, strengthening it (Fejerskov et al, 1990). The strength makes it more resistant to acid demineralization through its high electronegativity, and this is the reasoning behind fluoridation of water supplies. However, there has been debate around the benefits of fluoridation of water supplies (Hamilton, 1992) and the adverse effects of chronic low doses of fluorine are unclear, as some believe that the effects are deleterious even near current safe drinking water levels (Connett, 2007).

The goals of this paper are to: (1) outline the current state of the literature on the toxicological properties of fluorine and relevant compounds within human populations and (2) use this knowledge to provide an overview of fluoride’s toxic impacts on human health.

Exposure of humans and animals to fluoride can occur from high levels in groundwater, residential or industrial spills, and natural sources such as volcanic smoke and ash (Edmunds and Smedley, 2013), and even within foodstuffs, but varies widely geographically.  This paper will focus on the impacts of fluorine on human impacts. Although the impact of environmental fluoride on wildlife is an area of concern and active research, an assessment of the overall exposure and toxic effects of fluoride on wildlife is not available (Azorit et al, 2012), so the population of interest was selected to be humans.

II.                Exposure

Fluorides naturally occur in the earth’s system, and can cycle through reservoirs, similar to the way nitrogen, water and carbon cycle, which impacts the regions in which populations can be exposed to fluoride. Globally, concentrations of fluorine in surface waters are around 300 µg/L. Surface waters can become concentrated if hydrothermal interaction with fluoride-containing source rocks occurs. This fluorine is commonly derived from weathering of the minerals in earth’s crust, which has a fluorine abundance of 625 mg/kg (Edmunds and Smedley, 2013).  Ranges of detectible fluorine in worldwide drinking water can be from 0.1 to 10 mg/L; a map of predicted geogenic fluoride concentrations above the WHO guideline is shown in Figure 1. The WHO guideline for fluoride in drinking water is 1.5 mg/L (WHO, 1984), and drinking waters are commonly fluorinated to 1.0 mg/L concentrations.

Figure 1 – Predicted probability of geogenic groundwater fluoride with concentrations greater than the WHO guideline of 1.5 mg/L. Note the presence of an equatorial “fluoride belt” due to the presence of igneous and metamorphic rock structures (Amnin et al, 2008).
In air and rain, fluorine is found in low concentrations, except near coal-fired power plants or as industry-related aerosols (e.g. smoke from aluminum smelting or phosphorus fertilizer plants, (EPA, 1998)). In soils, the values can range from 200 to 300 ppm (without external contamination). The affinity of fluorides for soils is due to the tendency of most fluorine compounds to association with other ions, including substituting for OH- ions in clay structures. Due to this environmental distribution, foods and drinks can also be sources of naturally high levels of fluoride. For example, tea plants can accumulate fluoride in their leaves, and brewed teas can contain high levels of fluorine. Also, medical and dental products such as fluorinated toothpaste and antifungal medicines such as flucytosine contain fluoride. Finally, industrial workers may come into contact with fluorine in the form of hydrogen fluoride, which is commonly used to etch optical components and silicon computer chips (ATSDR, 2013).

The most likely routes of exposure for fluorides are through: (1) groundwater with naturally high concentrations of fluorides, especially those in contact with fluorapatite, (2) acute poisoning from absorption through repertory tract or skin if gaseous HF is released in an industrial environment and (3) chronic exposure of low doses through ingestion of fluoride-containing products such as toothpaste, and some fluoride containing products (Smith et al, 1993).

Oral Route of Exposure
Fluorides are commonly consumed via the oral route, as since fluoride is abundant in soils and plants, we inevitably ingest a small amount 1.0 – 3.0 mg/day on average, depending of dietary differences (Burt 1992). This amount is a larger concern for children, but is dependent on the presence of calcium in the water, as fluoride with readily bind with calcium in aqueous solution. The predominant source of fluorides daily intake for global populations is through drinking water (Murray, 1986), but sometimes diet can provide higher dosages of fluorides (WHO, 2006). At the same time, a diet high in calcium can provide a buffer against ingested fluoride. Either way, a good estimate of the total daily fluoride exposure through drinking water is 0.6 mg per adult per day in a non-fluorinated area, and 2 mg per adult per day in a fluorine-amended water supply area (WHO, 1984). Areas in China where cooking with high fluoride coal can contaminate food with high levels of fluorine have estimated oral intakes of 9.63 mg per adult per day (WHO, 2006).

Respiratory Route of Exposure
Airborne concentrations of fluorides in North America are viewed as “negligible” at a maximum of 0.04 mg of fluoride per day (Burt, 1992), but can rise to 1.4 mg of fluorine/m3 near industrial coal plants (Murray, 1986). However, most exposures of fluorides occur within industry or at the workplace, due to exposure to either hydrogen fluoride of hydrofluoric acid (where the latter is HF in aqueous form), and very limited documented exposure to pure fluorine (as its high reactivity leads to quick bonding with ambient water to form HF). Inhalation of hydrogen fluoride can cause burns along the respiratory tract, as occurred with a set of German industrial workers exposed to the gas. Nasal, bronchial and eye irritation and pulmonary hemorrhages were noted, as well as an increased risk of purulent tracheobronchitis (Bruan et al, 1984). Fluorine gas is similarly irritating, and both can also create systemic changes in electrolyte concentration (such as a decrease of Ca2+ concentration and subsequent heart impacts), as the fluorine enters systematic circulation.

Dermal Route of Exposure
Due to the high reactivity of the fluorine ion, hydrogen fluoride can produce dermal degradation and burns. Since fluorine ions will bond with intercellular calcium, the calcium near nerves will deplete, causing local nerve endings to continuously release potassium and discharge frequently (Bertolini, 1992). This causes a characteristically strong pain response in those exposed. Aqueous hydrogen fluoride can deliver mobile fluorine deep into the skin, and pain doesn’t directly correlate with exposure at high levels, as delayed effects are commonly seen (Bertolini, 1992).

Populations Most at Risk
Millions of people are exposed to fluorine in the global population, predominantly through drinking water supplies which are naturally enriched in fluorides (WHO, 2006). Drinking water is also the main source of fluoride intake by humans, given a lack of concentration industrial exposures. An estimated 200 million people currently rely on water with a concentration higher than the WHO limit of 1.5 mg/L (Amini et al, 2008). The occurrence of fluorosis is in part increased by calcium deficient diets (Murray, 1986), and much of the burden of this disease exists in India, China, Tanzania, Mexico, and Argentina, among other locations (Amini et al, 2008).  Therefore, the populations at risk are: (1) those exposed to high levels of fluoride in drinking water and (2) those exposed to fluorides in an industrial setting or due to industrial releases or pollution.

III.             Absorption
Fluorides can be absorbed through many different pathways in the human body including the gastrointestinal tract, lungs, and skin (ATSDR, 2003). Due to the high reactivity of fluoride, it is commonly associated with either hydrogen (as HF) or sodium (NaF or Na2SiF6), though it will dissociate and across multiple biological membranes to exhibit toxic actions (ATSDR, 2003).

Approximately 75-90% of orally ingested fluoride is absorbed, as all fluorides are converted into HF in the highly acidic stomach and can pass through the intestinal lining in that form (WHO, 2006). These compounds are rapidly absorbed through the stomach and intestines through passive diffusion, and blood plasma levels peak 30 to 60 minutes after ingestion (Ekstrand et al, 1978). Absorption of fluoride compounds are in part a function of the dose (diffusion limited), pH of the stomach (higher pH leads to more HF and faster absorption), the rate of gastric empting and the amount of ambient calcium and magnesium (as binding agents). The rate of stomach empting can increase the exposure in the upper gastrointestinal tract, and thereby increase absorption. Similarly, the presence of ions such as calcium and magnesium, and even aluminum decreased fluoride absorption (Stookey et al 1964)

Inhaled hydrogen fluoride can also provide a source of fluorides in systemic circulation, especially in blood. Absorption occurs predominantly through the upper respiratory tract (as suggested by rat studies by Morris and Smith, 1982), and had absorption rates from inhaled air of almost 100% for exposures from 30 to 176 mg fluoride/m3. Full blood diffusion of the fluorides occurred within 40 minutes, and the concentrations correlated extremely closely with inhaled fluoride (R2= 0.98, p<0.01) (Morris and Smith, 1982). Similarly, exposure to inhaled dusts containing hydrogen fluoride and fluoride-bearing dusts, as shown in urinary output of fluoride by aluminum production workers in the potroom was absorbed (Søyseth, V., et al. 1994), through a quantification of the rate and extent of absorption has not been documented for particulate fluorides (ATSDR, 2003).

Dermal exposure to fluorides such as hydrofluoric acid results in rapid penetration of fluoride ions into the skin, and if high amounts are present, large levels of cellular necrosis can occur along with bone decalcification (e.g. Dale, 1951, among others). The rapid adsorption of fluorine into the tissues can create systematic problems after dermal contact, but the percent of absorption has not adequately been reviewed (ATSDR, 2003). Similarly, no separation between HF (g) inhalation exposure and whole-body dermal fluorine exposure was made in the literature (ATSDR, 2003) though most exposures occur as joint dermal-inhalation impacts (Bruan et al, 1984).

Blood-Brain Barrier & Placental Protection
The blood brain barrier is effective in preventing the transfer of fluorides into the central nervous system, shown in studies of both ewes where brain fluoride concentrations did not exceed 10% of plasma concentrations (Whitford et al, 1979). However, fluoride will transfer across the maternal placenta. At low levels, the baby’s fluoride level was 60% of the mother’s, though this trend decreased at higher concentrations, suggesting a partial placental barrier (Gupta et al, 1993). This has impacts on developmental changes, as the growing baby is at risk of incorporating the fluorides into the bone structure. On the other hand, fluoride is not well transferred from plasma into breast milk (Ekstrand et al 1981). A dose of 1.5 mg sodium fluoride did not produce a rise in breast milk fluoride concentrations after three hours, and levels of fluoride in human milk commonly range from 5 to 10 µg/L (Gupta et al, 1993).

IV.              Distribution
There was limited data found the distribution of fluoride in human tissues via non-oral or dermal routes, likely due to the propensity for the fluorine to quickly move into the blood and plasma streams after exposure (Whitford, 1990) and the high prevalence of research on oral exposures (ATSDR, 2003).

In general, around 99% of the fluoride in the body at any given time can be found in bones and teeth (Hamilton 1990), along with the pineal gland which can also accumulate fluoride. Fluoride ions are incorporated into bone as they substitute for the hydroxyl ion in hydroxyapatite to form hydroxyfluroapatite (Ekstrand et al, 1977). No matter what the route of exposure is, some fluoride is deposited into teeth, and smaller amounts are distributed into soft tissues, and excreted in the urine, sweat and saliva. Fluoride distributes between the plasma and blood, with plasma levels over two times that of blood levels (Whitford, 1990), and limited protein binding, and a half-life within the plasma compartment of two to nine hours in a dual compartment model (Ekstrand et al, 1977, Figure 3).

Figure 3 – The two-box compartment model describing fluorine flux through measured plasma fluoride concentrations (ng/mL) in humans.
 e.g. plasma [fluoride] ß àbone/teeth/soft tissue
The lines compare the three and two-box models, with the two box model having a better coefficient of fit (Ekstrand et al, 1977).

Target Organs & Concentration of Fluoride
The primary target organs for fluoride are bones, lungs and teeth, with some emerging effects on the functioning of the kidneys at 1 ppm concentrations in rats (Tsunoda et al, 2005). Fluoride was shown to have a very limited impact on the central nervous system and live in rats (Tsunoda et al, 2005). As tissue fluoride levels are not regulated by the body’s homeostatic functions, the fluoride can move quickly through soft tissue and settle into bone. The level of distribution into bone is influenced by age, past fluoride exposure, and the rate of bone dissolution (which relates to nutrition status; Desmarais, 2014). The concentration of fluoride uptake in bone is related to the rate of bone growth, which decreases with age; as such, infants absorbed 68.1% to 83.4% of fluoride supplements, where adults only retained 55.3% from the same supplement (Ekstrand et al, 1994).  The concentration of fluoride within the teeth can produce fluorosis, a staining and disruption of the chemical formation of enamel (Figure 4).
Figure 4 – The progression of fluorosis of the tooth enamel, where fluoride replaces either the OH- or HCO3- ions to create hydroxyfluorapatite. Severe fluorosis can lead to dental problems, especially if during tooth formation (1-8 years old) including cracking and chipping of teeth (Image source:

V.                 Metabolism & Excretion
Fluoride metabolism is thought to be mainly through distribution and storage of the toxicant (Whitford, 1994), as fluorine is not bio-transformed directly by the body (US DOH, 1991). The primary route of removal of fluoride from plasma and blood is through the replacement of negatively charged ions (e.g. OH- or less commonly HCO3-) in the hydroxyapatite mineral structure of bone (Figure 5). It can also associate with aluminum, calcium, beryllium and magnesium in the body (Whitford et al, 1987).
The main location of metabolism through apatite incorporation is through the periosteal of the long bones, specifically in cancellous bones matter, at the rate of 50% of total daily fluoride being absorbed by the bones within 24 hours of exposure. After absorption, the remaining fluoride is excreted through either sweat and urine (< 1%) or urine (~50%) (Whitford, 1994; Ayoob and Gupta; 2007).  The high rate of absorption in these cancellous bone areas, especially during bone growth, is due to the high concentration of blood supply in those areas, which normally provides calcium ions, and the high surface area of bone crystallites. The rate of absorption of fluorine into bone is much higher than calcium, and so for children the rate of incorporation of fluorine into bone can be much greater than 50% (Whitford, 1994), increasing the level of bone metabolism and decreasing excretion of free fluorine. Once attached to bone, it is very strongly bond but not irreversibly so, as it is housed in two reservoirs (1) a rapidly exchanged pool in the hydration shells of bone crystallites, and (2) a slowly exchangeable pool which can be released from bones during bone reabsorption, bone remodeling, or during bone healing (Buzalaf, 2011). This pattern is consistent for all routes of absorption of fluorine and hydrogen fluoride (US DOH, 1991).

Figure 5The main features of fluoride metabolism in the human body are plotted across a curve of typical plasma concentrations. Not the similarity in shape to experimental concentrations in Figure 4. The main excretion pathway through urine is shown larger than the secondary pathways (feces, sweat) (Whitford, 1994).

Molecules which contain fluorine tend to have enhanced lipophilicity and increased passive diffusion through biological membranes, which is one of the reasons why fluorine is prominent in medicines developed today (Park et al, 2001). These organic fluorine-bearing molecules have various actions in the body, and many Phase I/Phase II biotransformation pathways. The p450 enzyme can be inhibited by the presence of fluorine in a bond, which can increase the residence time of a medicine in the body (Park et al, 2001; Bohm et al 2004). However, reviews of the metabolism of fluorine-derived medicines are beyond the scope of this paper, due to their high number and varied mechanisms, but much research has been completed in that field (e.g. Bohm et al, 2006; Hagmann et al, 2008; Park et al, 2001; etc).

Almost all of the excretion of fluorine from the body is through urine from the kidney, as fluoride is filtered by the glomerulus and partially re-absorbed (10-70%, similar to other negatively charged ions) by the tubular system (ATSDR, 2003). The extent of reabsorption is related to pH, and is approximately 30 to 40 mL/min in average adults (Buzalaf, 2011). Renal clearance of fluoride is directly related to pH, as at lower pH fluorides exist predominantly as HF, which can be excreted, whereas at higher pH values, HF would dissociate and fluorine would return to circulation (Whitford et al, 1976).

Substances that would inhibit these processes of metabolism and excretion would be agents which could increase urinary pH (e.g. ammonia), which could slow the primary excretion pathway for fluorine (urination) (Tannen, 1978). Similarly, any oliguric agents that could slow the output of urine could also decrease the rate of excretion. The secondary excretion pathways of fecal and sweat excretion are negligible in terms of inhibition of excretion. The presence of enhanced calcium in both blood serum and in the stomach can bind systematic fluoride and decrease the fluoride concentration. No reliable data was found on interactions that directly impact the negative effects of fluoride in the body (ATSDR, 2003).

VI.              Toxic Effects
The process which metabolizes fluorides from the body is the same process which can produce many of its toxic effects on the human body – the substitution of fluorine for other ions, such as OH- in bone minerals. Fluoride can substitute into the structure of the bones and teeth, and provide both positive and negative impacts depending on: the dose, age of the populations exposed, and patient nutrient status (NAS, 1997).

Chronic Effects - Fluorosis of Teeth
Dental fluorosis (as shown in Figure 4) can occur as the adult teeth are developing in the jaw and before they erupt into the mouth (age < 8 years). The no-observed-adverse-effect level (NOAEL) was identified to be 0.10 mg/kg/day for moderate enamel fluorosis in children from 0-8 years old (NAS, 1997). Fluorosis of teeth is related to chipping and cracking of the dental surface, which can relate to endpoints sepsis and localized inflammation if paired with poor dental hygiene, and possibly social ostracizing. Fluoride also may inhibit amelogeninase, a calcium-dependent metalloenzyme through competitive inhibition for calcium which is utilized in enamel formation (Whitford, 1997).

Chronic Effects - Fluorosis of Bones
Fluorine can also substitute for ions within the structure of bones, similar to fluorosis in teeth. Fluoride blood plasma and bone strength have a bi-phasic relationship in rats (Turner, 1992), where both extremely low and high concentrations of fluoride can have a negative impact in bone strength, suggesting that the quality of new bone with high levels fluoride inclusions is lower. The mechanism for this toxicity is an alteration at the interface between the collagen and the mineral, where fluorine forms wider crystals, which are not as well-linked to collagen fibers and have decreased mechanical strength (Turner, 1997). Therefore, although fluorosis can increase bone density and strength in low doses, as chronically high doses (~ 1.5 mg/L concentrations in areas of high water intake; near equator) negative impacts on bones can occur. Beyond physiochemical changes, fluoride can impact the immune system, inhibiting the osteoblasts which would commonly resorb bone tissue for both maintenance and repair of bones (Chachra et al, 1999). Fluorine is both toxic to individual osteoblasts and decreases the amount of bone resorbed by osteroclasts (Chachra et al, 1999).  This is of greater concern with those with weakened immune systems and children (ATSDR, 2003), and those with poor nutrition (Teotia et al, 1998). As such, fluoride in the drinking water of the developing world may be a prime candidate for a global public health intervention.

Acute Toxic Effects – Dermal & Respiratory Irritation & Necrosis
The most relevant toxic effects to those working with fluorides in an industrial setting are most likely the dermal and respiratory impacts. Exposure to low concentrations of HF (> 0.5 ppm) via inhalation can produce irritation, where higher concentrations can produce pulmonary edema, hemorrhaging, necrosis and even pulmonary collapse (Bruan et al, 1984). Dermal exposure to aqueous HF can cause extensive necrosis and even systemic fluoride intoxication due to quick absorption through dermal route. Fluoride intoxication is when fluorine alters electrolyte concentrations (e.g. Figure 5; altering of calcium concentrations and cardiac changes), (Barbier et al, 2011).

Carcinogenic Effects
Some community based studies have found associations between drinking from a fluorinated water supply and cancer, including osteosarcoma or bone cancer (Cohn, 1992; Erickson, 1978; among others). Some studies on rats have found a weak fluoride-mediated increase in osteosarcomas in males rats (ASTDR, 2003). Most studies show no significant association between fluorides and cancer, and the International Agency for Research on Cancer (IARC) has determined that carcinogenic nature of fluorides are not classifiable, which means the data are insufficient to make an evaluation (IARC, 1987). 
Genotoxic Effects
Results across the literature have been inconsistent, but a consensus is forming that at toxic levels (>10 μg/mL, and usually >40 μg/mL), there may be a general inhibition of enzymes, including DNA polymerase (Caspary et al. 1987), which may impact the p53 generation. Recent results after the publication of the ATSDR suggest that even at daily dosages of millimolar concentrations, fluoride can induce apoptosis, inhibit protein secretion/ synthesis, and generate oxidative stress and reactive oxygen species (ROS) through microchondrial interactions (Figure 5).
Figure 5 – Multiple mechanisms of fluoride toxicity occur, with signaling in the cardiac system being of the greatest acute importance (as Ca2+ availability can lead to heart rhythm changes), but alterations to oxidative stress, cell respiration, and DNA changes can occur (Barbier et al, 2011).

Developmental Effects
Current data on fluorides potential to induce developmental effects is inconclusive (ATSDR, 2003). However, recent studies by Lu et al. (2000) suggested that a decrease in IQ scores was noted in children in China exposed to high fluoride from coal mining soot. However, in this study there was no control for other contaminants, such as lead, in the soot. Limited data suggest that fluoride at therapeutic drinking water levels does not impact the developing fetus, as the body can regulate fluoride passage through the placenta. However, more research is suggested on developmental effects of fluoride in high concentrations, especially as a co-contaminant with arsenic, as is commonly endemic in some developing countries (Foster et al, 2008).

Toxic Effects on Organ Systems
The most primary toxic effects after inhalation of fluorine or hydrogen fluoride are the inflammation and disruption of the trachea, bronchi and alveoli. The respiratory tract is a primary target organ for gaseous fluorine (ATSDR, 2003).  Inhalation of hydrogen fluoride can produce symptoms such as irritation, pulmonary edema, hemorrhaging, necrosis and even pulmonary collapse (Bruan et al, 1984), and depend on concentration and duration of exposure. However, in cases of exposure to gaseous HF where death occurs, toxic effects on the respiratory system are commonly the culprit (Figure 6).

Figure 6 – Toxic effects of fluorine on (A) the lung tissue (B) the trachea and (C) the alveoli after exposure to HF (g) (images from Bruan et al, 1984; diagram from

Toxic effects on the skin are similarly intense, as fluoride is highly lipophilic and can easily pass through the skin. Dermal exposure to aqueous HF can cause extensive necrosis and even systemic fluoride intoxication due to quick absorption through dermal route. Fluoride intoxication is when fluorine alters electrolyte concentrations (e.g. Figure 5; altering of calcium concentrations and cardiac changes), (Barbier et al, 2011). Less than 1% of the distributed fluorine stays in tissues after 24 hours (Whitford, 1994), so removal of the source chemical and immediate topical application or intravenous administration of calcium gluconate is paramount (Bruan et al, 1984).

Also related are the toxic effects on the ocular system, which can be irritated by 0.5 – 4.5 ppm HF gas. Necrosis of ocular tissue can occur with exposure to aqueous HF, but data on toxic ocular impacts from high systemic levels of fluorides are extremely limited (ATSDR, 2003). The final organ system where toxic effects of fluorides are paramount is within the renal system. The kidneys are sensitive to disruption by ingested fluoride, as they will concentrate HF in order to excrete it from renal tubules. In rodents, necrosis of renal tubules occurred after high dosage of hydrofluoric acid was administered. In general, renal impairment occurs at higher concentrations than the respiratory effects (Keplinger and Suissa 1968). Concurrent kidney stress may lead to increased levels of necrosis, such as exposure to industrial solvents, and co-contamination should be monitored closely. Some necrosis was also noted in the liver parenchymal tissue in these studies, but insufficient human data exists on liver damage (ATSDR, 2003).

VII.           Summary
As oral fluoride exposure effects over 200 million people (Amini et al, 2008), and a majority of rural populations rely on groundwater as their drinking water source (Foster et al, 2008), the impact of hydrological and climate changes on the distribution of fluoride may be drastic. Changes in the magnitude of fluoride concentrations both orally and through other exposure routes could have a myriad of impacts on human populations. Similarly, the use of fluorine in medicine development is showing no sign of slowing (Figure 7), and the release of compounds into wastewater after ingestion is another important emerging source of fluorine to the environment.

The very nature that makes fluorine useful as a metal flux and a medical additive – its high electronegativity and affinity for bonding – are the same root of its toxic effects in humans. Fluorine is truly a savage (but useful) beast among the elements, and a double edged sword as a triumph of public health weighted by a risk possible harm. In other words:

“All substances are poison; there is none which is not a poison. The right dose differentiates a poison from a remedy.” ~Philippus Aureolus Theophrastus Bombastus von Hohenheim-Paracelsus, 1567

Figure 7 – A graph of all launched drugs from 1957 to 2006 containing fluoride (red bars) verses total number of drugs launched; there has been a notable increased of the percentage of fluorine containing drugs in recent times, which is expected to continue (Hagmann et al, 2008).

Agency for Toxic Substances and Disease Registry (ATSDR). 2003. Toxicological profile for Fluorine. Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service.

Ayoob, S., and A. K. Gupta. "Fluoride in drinking water: a review on the status and stress effects." Critical Reviews in Environmental Science and Technology 36.6 (2006): 433-487.

Azorit, C., et al. "Periodontal disease and fluoride bone levels in two separate Iberian red deer populations." Animal Production Science 52.8 (2012): 774-780.

Barbier, O., L. Arreola-Mendoza, and L.M. Del Razo. 2011 Molecular mechanisms of fluoride toxicity. Chem Biol Interact. 2010 Nov 5;188(2):319-33. Epub 2010 Aug 3.

Bertolini JC. Hydrofluoric acid: a review of toxicity. J Emerg Med. Mar-Apr 1992;10(2):163-8.

Böhm, HansJoachim, et al. "Fluorine in medicinal chemistry." ChemBioChem 5.5 (2004): 637-643.

Burt, B. A. "The changing patterns of systemic fluoride intake." Journal of dental research 71.5 (1992): 1228-1237.
Braun, J., H. Stöss, and A. Zober. "Intoxication following the inhalation of hydrogen fluoride." Archives of toxicology 56.1 (1984): 50-54.

Buzalaf, M. A. R., and G. M. Whitford. "Fluoride metabolism." (2011): 20-36.

Caspary WJ, Myhr B, Bowers L, et al. 1987. Mutagenic activity of fluorides in mouse lymphoma cells. Mutat Res 187:165-180.

Chachra D, Turner CH, Dunipace AJ, et al. 1999. The effect of fluoride treatment on bone mineral in rabbits. Calcif Tissue Int 64:345-351.

Cohn PD. 1992. An epidemiologic report on drinking water and fluoridation. Environmental Health Service. New Jersey Department of Health.

Dale, R. H. "Treatment of hydrofluoric acid burns." British medical journal 1.4709 (1951): 728.

Desmarais, Anne Marie. “CEE-167: Toxic Responses.” Toxicology. Tufts University. 10-15-2014.

Dolbier Jr, William R. "Fluorine chemistry at the millennium." Journal of fluorine chemistry 126.2 (2005): 157-163.

Edmunds, W. Mike, and Pauline L. Smedley. "Fluoride in natural waters." Essentials of medical geology. Springer Netherlands, 2013. 311-336.

EPA. 1998. Background Report: AP-42 Section 12.1. Primary aluminum.

Emsley, John. Nature's building blocks: an AZ guide to the elements. Oxford University Press, 2011.

Ekstrand, J., et al. "Pharmacokinetics of fluoride in man after single and multiple oral doses." European journal of clinical pharmacology 12.4 (1977): 311-317.

Ekstrand J, Ehrnebo M, Boréus LO. 1978. Fluoride bioavailability after intravenous and oral administration: Importance of renal clearance and urine flow. Clin Pharm Ther 23:329-337.

Ekstrand J, Boreus LO, de Chateau P. 1981c. No evidence of transfer of fluoride from plasma to breast milk. Br J Med 283:761-762.

Erickson JD. 1978. Mortality in selected cities with fluoridated and non-fluoridated water supplies. N Eng J Med 298:1112-1116.

Fejerskov, O., F. Manji, and V. Baelum. "The nature and mechanisms of dental fluorosis in man." Journal of dental research 69 (1990): 692-700.

Foster, Stephen, et al. "Groundwater in rural development: facing the challenges of supply and resource sustainability." (2008).

Gupta S, Seth AK, Gupta A, et al. 1993. Transplacental passage of fluorides. J Pediatr 123:139-14

Greenwood, N. N.; Earnshaw, A. (1998). Chemistry of the Elements (2nd ed.). Oxford: Butterworth Heinemann. ISBN 0-7506-3365-4.

Hagmann, William K. "The many roles for fluorine in medicinal chemistry." Journal of medicinal chemistry 51.15 (2008): 4359-4369.

Hamilton IR. 1990. Biochemical effects of fluoride on oral bacteria. J Dent Res 69(special issue):660667.

Hamilton M (1992) Water fluoridation: a risk assessment perspective. J Environ Health 54:27–32

IARC Monographs, Fluoride, 27, 237-303, 1987.

Jowsey, Jenifer, and B. Lawrence Riggs. "Effect of concurrent calcium ingestion on intestinal absorption of fluoride." Metabolism 27.8 (1978): 971-974.

Keplinger ML, Suissa LW. 1968. Toxicity of fluorine short-term inhalation. Am Ind Hyg Assoc J 29(1):10-18.

Kleinfeld M. 1965. Acute pulmonary edema of chemical origin. Arch Environ Health 10:942-946.

Lu Y, Sun ZR, Wu LN, et al. 2000. Effect of high-fluoride water on intelligence in children. Fluoride 33(2):74-78.

Morris, John B., and Frank A. Smith. "Regional deposition and absorption of inhaled hydrogen fluoride in the rat." Toxicology and applied pharmacology 62.1 (1982): 81-89.

Messer HH, Ophaug RH. 1993. Influence of gastric acidity on fluoride absorption in rats. J Dent Res

Murray, John J., and World Health Organization. "Appropriate use of fluorides for human health/edited by JJ Murray." (1986).

NAS. "Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride." (1997) National Academy of Sciences. Institute of Medicine. Food and Nutrition Board.

Park, B. Kevin, Neil R. Kitteringham, and Paul M. O'Neill. "Metabolism of fluorine-containing drugs." Annual review of pharmacology and toxicology 41.1 (2001): 443-470.

Søyseth, V., et al. "Relation between exposure to fluoride and bronchial responsiveness in aluminium potroom workers with work-related asthma-like symptoms." Thorax 49.10 (1994): 984-989.

Suess, Hans E., and Harold C. Urey. "Abundances of the elements." Reviews of Modern Physics 28.1 (1956): 53.

Smith, Frank A. "Fluoride toxicity." Handbook of Hazardous Materials (1993): 277-284.

Smith, Margaret Cammack, Edith M. Lantz, and Howard Vernon Smith. "The cause of mottled enamel, a defect of human teeth." (1931).

Stookey, EL Dellinger, JC Muhler; In vitro studies concerning fluoride absorption. Proc. Soc. exp. Biol. Med., 115 (1964), pp. 298–301.

Teotia, M., S. P. S. Teotia, and K. P. Singh. "Endemic chronic fluoride toxicity and dietary calcium deficiency interaction syndromes of metabolic bone diease and deformities in India: Year 2000." The Indian Journal of Pediatrics 65.3 (1998): 371-381.

Turner CH, Akhter MP, Heaney RP. 1992. The effects of fluoridated water on bone strength. J Orthop Res 10(4):581-587

Turner CH, Garetto LP, Dunipace AJ, et al. 1997. Fluoride treatment increased serum IGF-1, bone turnover, and bone mass, but not bone strength, in rabbits. Calcif Tissue Int 61:77-83

Tsunoda, Masashi, et al. "Changes in fluoride levels in the liver, kidney, and brain and in neurotransmitters of mice after subacute administration of fluoride." Fluoride 38.4 (2005): 284-292.

Toon, Richard. "Fluorine, an obsession with a tragic past." Education in Chemistry 48.5 (2011): 148.

US DOH. Review of Fluoride: Benefits and Risks. Ad Hoc Subcommittee on Fluoride. US Public Health Service, Department of Health and Human Services, Bethesda MD 1991.

Whitford GM, Pashley DH, Reynolds KE. 1979. Fluoride tissue distribution: Short-term kinetics. Am J Physiol 236:F141-148.

WHO (World Health Organization) (1984) Guidelines for drinking water quality, Vol 3. Drinking water quality control in small community supplies. WHO, Geneva.

World Health Organization (WHO), in: K. Bailey, J. Chilton, E. Dahi, M. Lennon, P. Jackson, J. Fawell (Eds.), Fluoride in Drinking-water, WHO Press, Switzerland, 2006.

Monday, November 23, 2015

Is development as an enabling condition for terrorism?

Is development an enabling condition for terrorism?

Enabling conditions have been a useful framework across many academic disciplines, as moving beyond the mechanistic cause and effect framework to include more complex issues tends to better reflect observed outcomes. These have been adapted into the fields of psychology (Cheng and Novick, 1991), biology (Ruiz-Mirazo et al, 2008), and many other fields (Tinsley and Faunce, 1980; Moore and Rodger, 2010). In complex systems, concepts like necessary and sufficient and linear-styled thinking are limited, as the scales in time and space is too variable, especially when systems are coupled with social factors

With the recent terrorist attacks in Paris, resulting in over 120 deathswe can reflect on the global reach of the effects that ripple through social systems. In the wake of such a tragedy, it is important to understand the complexity of the task of identifying risks of national security, and the sensitive balance between civil liberties and the steps taken to ensure the safety of a nation's citizens. No matter where the loss of life occurs, it is a tragedy for all, both in the loss of unique individuals and all the benefits they may have brought to the world. 

Figure 1 The first image which comes up when one searches "terrorism" in Google Images. The image shows some commonalities of terrorist groups: a small group of gunman, isolated, and anonymous in silhouette (Image source:

However, it's easy to look back with hindsight, or to comment hastily with an agenda in mind. I suggest that it's potentially better to understand the root causes, or in absence of that, the enabling conditions for a terrorist group to form. In epidemiology, this is commonly referred to as primary prevention - preventing the development or exposure which causes the disease. 

It should be noted that I don't expect to break new ground with this blog post, however I think an brief overview of the research between development and terrorism is warranted. I will go through this in a few short summaries over the next few weeks. From my previous post linking global protests with networks of MNCs, we see that social movements even on a local level can have wide reaching implications, especially in densely connected networks.  

We know that the development of terrorism occurs within coupled social, economic and cultural systems, and across many contexts. Models have shown limited impact of economic development on the presence of terrorism (Piazza, 2006), although the study found that factors such as state repression, party politics, and ethno-religious diversity is more predictive.

Some have suggested that the political structures within Iraq are the dominant factor, with the former ambassador to Syria Robert S. Ford stating that only a political solution which fully incorporate Sunnis into Iraq would be successful (Source: NYTimes). If the regression model above by Piazza (2006) is valid globally, the influence of political repression by states is especially important, suggesting that an inclusive culture at the federal level would help to prevent the radicalization which is one condition which can create fertile soil for more extreme ideologies to form. Similar studies have shown that the both ideologies and the amount of territorial area controlled by a group is most predictive of the projected deaths of a group. Groups that were both religious, ethno-nationalist, and controlled territory were the most likely to kill in a regression of data from 1998 to 2005 (Figure 2; Asal and Rethemeyer, 2008).

Figure 2 Predicted lethality of terrorist groups estimated by linear regression given ideology, size, and control of territory, note the lack of effect modification of the variables on projected deaths by organizational size (Asal and Rethemeyer, 2008).

This is a complex question, which might be inappropriate to answer in the length and rigor of a blog post. Knowing this, I think it could be asked again - can development be an enabling condition for terrorism? Should we search for enabling conditions for these complex problems, or it is a waste of time? Does the reflexive response to such global tragedies (including such attacks in a Kenyan mall, and many others) help or harm society? 

And one final question - do blog posts such as this one add "fuel to the fire", such as the news coverage of school shootings - do we need a constant re-framing of the news events in order to fully understand a problem (Chyi and McCombs, 2004)? Feel free to comment below. 


Asal, Victor, and R. Karl Rethemeyer. "The nature of the beast: Organizational structures and the lethality of terrorist attacks." The Journal of Politics 70.02 (2008): 437-449.

Cheng, Patricia W., and Laura R. Novick. "Causes versus enabling conditions." Cognition 40.1 (1991): 83-120. [link]

Chyi, Hsiang Iris, and Maxwell McCombs. "Media salience and the process of framing: Coverage of the Columbine school shootings." Journalism & Mass Communication Quarterly 81.1 (2004): 22-35. [link]

Moore, Susan A., and Kate Rodger. "Wildlife tourism as a common pool resource issue: Enabling conditions for sustainability governance." Journal of Sustainable Tourism 18.7 (2010): 831-844. [link]

Piazza, James A. "Rooted in poverty?: Terrorism, poor economic development, and social cleavages 1." Terrorism and Political Violence 18.1 (2006): 159-177. [link]

Ruiz-Mirazo, Kepa, Jon Umerez, and Alvaro Moreno. "Enabling conditions for ‘open-ended evolution’." Biology & Philosophy 23.1 (2008): 67-85. [link]

Tinsley, Diane J., and Patricia S. Faunce. "Enabling, facilitating, and precipitating factors associated with women's career orientation." Journal of Vocational Behavior 17.2 (1980): 183-194. [link]