Toxicological Chemistry of Chemicals PDF

TOXICOLOGICAL CHEMISTRY of CHEMICALS, Cont. Toxic Organic Compounds 1 Toxic Organic Compounds Synthetic chemicals
Most are derived from petroleum or natural gas
Types:  Polycyclic aromatic hydrocarbons (PAHs...

TOXICOLOGICAL CHEMISTRY of CHEMICALS, Cont. Toxic Organic Compounds 1 Toxic Organic Compounds Synthetic chemicals
Most are derived from petroleum or natural gas
Types:  Polycyclic aromatic hydrocarbons (PAHs)  Organochlorine insecticides  Organophosphate and carbamate insecticides  Organic herbicides  Dioxin contaminant of herbicides and wood preservatives 2 1  Polycyclic Aromatic Hydrocarbons (PAHs) 3 Polycyclic Aromatic Hydrocarbons (PAHs)
PAHs consist of fused benzene rings
Examples: 4 2  PAHs - Cont. Uses:
Only naphthalene is made commercially - used as precursor to plasticizers, insecticides, surfactants, etc)
Other PAHs don’t have uses Source:
Incomplete combustion of C-based fuel (coal, wood, diesel) - Diesel engine exhaust recently labeled “probable human carcinogen”
“Tar” of cigarette smoke
Surface of charred or burnt food; Smoked food NOTE: PAHs constitute 0.1% (= 1000 ppm) of airborne particulate matter 5 PAHs (Cont.) Health effects:
Carcinogenic to test animals  Probable human carcinogen Most notorious is benzo[a]pyrene Level in several urban sites in the Great Lakes exceeds the current guidelines
Bioaccumulates in the food chain => a worrisome pollutant 6 3  PAHs (Cont.) Baird, p. 365 7 PAHs (Cont.) Mechanism of PAH carcinogenity: Box 6-4, p. 363, Baird
Research showed that PAHs themselves are not carcinogenic  Their metabolic products are carcinogenic
Chemical transformation: (1) oxidation into an epoxide ring (2) Subsequent hydration produces the active carcinogen + H2O  Addition of H+ forms a stable cation that can bind to DNA, inducing mutations and cancer carcinogen 8 4 PAHs (Cont.) Environmental Chemistry of PAHs: Transport in the atmosphere
≤ 4 fused ring remain gaseous  Form degradation products upon reaction with free radicals in the air
> 4 fused ring have low vapor P  Condense and adsorb onto surface of soot and ash  They become respirable 9 PAHs - Environmental Chemistry (Cont.) Transport in the hydrosphere
Creosote, a coal tar derivative used as wood preservative, contains PAHs  Used in fishing docks (immersed in water) PAHs leach out Water pollution (Lobster, fatty tissues of fish, whales)
Oil spills from tankers, refineries and off-shore drilling sites also cause pollution of water with PAHs 10 5  Organochlorine Insecticides 11 Organochlorine Insecticides NOTE: The following information were taken from Baird, C. “Environmental Chemistry, 2nd ed. (2003), pp. 297-. Characteristic properties
Stable towards environmental degradation
Low solubility in water Properties responsible for their
High solubility in fatty materials bioaccumulation (hydrocarbon-like) in living matter
Relatively high toxicity to insects
Low toxicity to humans 12 6 Organochlorine Insecticides (Cont.) Example: HCB or hexachlorobenzene
Used as fungicide for cereal crops after WWII
Extremely persistent => Led to its widespread env’l contamination
Toxicity effect:  Carcinogenic to lab rodents  Probable human carcinogen 13 Organochlorine Insecticides (Cont.) DDT or para-dichlorodiphenyltrichloroethane Historical perspective:
1939: Paul Müller (Swiss) discovered DDT as insecticide [He later received the 1948 Nobel Prize in medicine and physiology] 14 7 DDT – Cont. Historical perspective: (Cont.)
During WWII DDT was used to combat insect-transmitted illnesses  Malaria Transmitted by mosquitoes  Yellow fever  Typhus => transmitted by body lice  Plague => carried by fleas
W.H.O. estimated that > 5M lives have been saved by DDT 15 DDT – Cont. Historical perspective: (Cont.)
After WWII, DDT became widely used as insecticide (accounted for 80 % of manuf. DDT)  Fruit trees  Vegetables  Cotton 16 8 DDT – Cont. Desirable properties of DDT as insecticide
Persistent chemical  One spraying lasted for weeks or years (depending on method of application)  Persistence due to its:
Low vapor pressure (low volatility) Resisted
Low reactivity to light and degradation; microorganisms transport
Low solubility in water 17 DDT – Cont. Environmental effects of DDT
Persisted in soil for several years  Biomagnified in the food chain
Some insect populations developed resistance
Affected the reproductive abilities of birds  Metabolic prod. interfered with a Ca-regulating enzyme  Very thin shells; Baby bird unable to survive
1962: Rachel Carson (biologist) published the “Silent Spring” Env’l problems associated with DDT
1973: EPA banned all DDT uses (except those essential to public health) 18 9  Accumulation and fate of DDT 19 DDT – Cont. Accumulation and fate of DDT  DDT levels accumulated in fatty tissues => higher levels in older trout 20 10  Accumulation and fate of DDT DDT in humans is slowly eliminated  Stored in human fat mostly as its metabolic product DDE Source: Toxic Chemicals in the Great Lakes and Associated Effects, vol 1, part 2. 1991 Ottawa, Canada: Minister of Supply and Services. 21 Organochlorine Insecticides - Analogs to DDT DDT Analogs
Same insecticidal properties as DDT
Reasonably biodegradable  No bioaccumulation
Best known is methoxychlor (insecticide)  Used domestically and in agriculture Controls flies; mosquitoes 22 11  Other Organochlorine Insecticides Lindane
Contains one of 8 isomers of hexachlorocyclohexane  Called gamma isomer = has insecticidal properties  Same isomer in medical preparations for lice and scabies control  Treatment of seeds and seedlings 23 Other Organochlorine Insecticides – Cont. Chlorinated cyclodienes
Aldrin, Dieldrin, Chlordane, Heptachlor, etc.  Used to control various pests:  Fire ants; cockroaches; termites; locusts Undesirable properties  Persistent chemicals; Bioaccum. due to solubility in fatty tissues Chlorinated  Caused liver cancer in test animals cyclodienes  Some are teratogenic Prohibited use in the U.S. 24 12  Modern Insecticides: Organophosphates and Carbamates 25 Organophosphate Insecticides - Esters, amides, or simple derivatives of phosphoric acid
Nonpersistent  Decompose within days or weeks
Much more acutely toxic to humans and other mammals than are organochlorines
Function as nerve poisons to insects  Inhibit enzymes in the insects’ nervous system 13 Organophosphate (Cont.) Undesirable properties
Exposure by inhalation, swallowing or absorption th/ the skin can lead to immediate health problems Clinical Signs (Organophospahe toxicity, http://www.michigan.gov/dnr/) Excess salivation, lacrimation, abdominal pain, vomiting, and diarrhea. Bronchoconstriction and an increase in bronchial secretions Involuntary irregular, violent muscle contractions and weakness of voluntary muscles. Death occurs as a result of respiratory failure.
Concentrates in fatty tissues 27 Carbamate Insecticides Carbamates
Nonpersistent  Decompose upon reaction with water, forming nontoxic products
Low dermal toxicity
Examples: Carbaryl; Aldicarb; Carbofuran  Lawn and garden insecticide  Low toxicity to mammals  Toxic to honeybees 28 14  Naturally-Occurring Pesticides 29 Natural Insecticides
Manufactured by plants as defensive mechanism against insects
Examples: Nicotine; Rotenone; Pheromones and Juvenile hormones Pyrethrins  Obtained from crysanthemum (certain species)  Have been used by humans for centuries Ex. Ground up dried flower heads used to control body lice during the Napoleonic times  Paralyze insects (like organophosphates) 30 15 Pyrethrins (Cont.) Desirable properties  Generally safe to use  Mode of action: Cause paralysis on insects Undesirable properties  Photodecomposition Synthetic pyrethrins = designed to withstand sunlight  Outdoor application  Names end in -thrin: Ex. Permethrin 31 Organic Herbicides 32 16 Herbicides
Prior to use of organic pesticides:  Inorganic compounds like sodium arsenate were used as weed-killers Toxic to humans; Persistent chemicals
Organic pesticides now dominate the market  High selectivity for certain plants Leave other plants unharmed 33 Organic Herbicides Triazines
Alternating N & C atoms in a six-membered ring
Useful triazine herbicides contain Cl and -NH2 or -NHR groups bonded to the ring carbon (next slide) 34 17  Triazines (Cont.)
Best known is atrazine Atrazine Mode of action (as herbicide)
Blocks photosynthesis  Higher plants (e.g. corn) are not affected because they rapidly degrade atrazine 35 Atrazines (Cont.) Uses
Kills grassy weeds in corn and soybean fields Undesirable properties
Concentrations can build up in dry soil => No moisture to degrade it  Can eradicate all plants  High levels used to clear vegetation to create parking lots
Widespread use can kill sensitive plants in water systems close to agricultural fields
A possible human carcinogen (EPA list) 36 18  Other Organic Herbicides Phenoxy herbicides
Introduced as weed-killers after WWII
Prepared from phenol
Examples: 2,4-D and 2,4,5-T 37 Phenoxy Herbicides (Cont.) 2,4-D & 2,4,5-T Uses
2,4-D: Control of broad-leaf weeds in lawns, golf course greens and agricultural fields
2,4,5-T: Clearing bush on roadsides and power line corridors Undesirable properties
Increased incidence of the cancer non-Hodgkin’s lymphoma among farmers in the Midwest who applied large quantities of 2,4-D 38 19  Dioxin Contamination of Herbicides 39 Cause of Dioxin Contamination Synthesis of 2,4,5-T Do this on the board 40 20 Cause of Dioxin Contamination (Cont.)
Trichlorophenol is a weak acid  Ionizes to a small extent into trichlorophenoxy ion  Self-reaction of phenoxy ion at high T produces “dioxin”  High T and high [phenoxide] => higher levels of dioxin formed Structure of real dioxin 41 Dioxin Contamination: Historical Perspective Agent Orange
A 1:1 mixture of 2,4-D and 2,4,5-T
Used as defoliant during the Vietnam war
Contains about 10 ppm dioxin as contaminant! HOW come? http://www.landscaper.net/agent.htm 42 21  Dioxin Nomenclature
The three-ring unit is called dibenzo-p-dioxin
Carbons shared between 2 rings (and thus are not bound to H) are not numbered --- can’t take any more substituent
C #ing follows a clockwise pattern from C-1 43 Dioxin Congeners Congeners
Members of a chemical family that differ only in the number and position of the same substituents
There are 75 dioxin congeners 44 22  Dioxin: Health and Environmental Effects Health Effects
One of the most toxic of all synthetic substances to some animals  LD50 of 0.6 ug/Kg body mass in male guinea pigs
The type and degree of its toxicity to humans is largely unknown  Known to cause a severe skin condition called chloracne Environmental Effects
A stable, persistent environmental pollutant
Emission product from incineration of organochlorine compounds 45 Dioxins “Dioxin” is a general term for a group of hundreds of chemicals that are highly persistent in the environment.  The most toxic compound is 2,3,7,8-tetrachlorodibenzo-p- dioxin or TCDD. TCDD structure. Image available at http://www.greener- industry.org/pages/chlorine/3chlorine_Issues. htm Reference: Dioxin Homepage at http://www.ejnet.org/dioxin/ 46 23  Dioxins Dioxin is formed as an unintentional by-product of many industrial processes involving chlorine, such as:  Waste incineration,  Chemical and chlorinated pesticide manufacturing,  Production of polyvinyl chloride (PVC) plastics and  Pulp and paper bleaching Dioxin was the primary toxic component of Agent Orange, was found at Love Canal in Niagara Falls, NY and was the basis for evacuations at Times Beach, MO and Seveso, Italy. Reference: Dioxin Homepage at http://www.ejnet.org/dioxin/ 47 In January 2001, the U.S. National Toxicology Program upgraded 2,3,7,8-TCDD from "Reasonably Anticipated to be a Human Carcinogen" to "Known to be a Human Carcinogen. Reference: Dioxin Homepage http://www.ejnet.org/dioxin/ 48 24  Levels of Dioxin in Food Supply (N. America) Image available at http://www.nrdc.org/breastmilk/diox.asp 49 Figure 7 shows that dioxin and furan levels in breast milk collected between 1996 and 1999 from women in the Aluoi Valley in central Vietnam were about six times higher than those in breast milk collected in 1988 in the city of Hanoi in northern Vietnam, where no Agent Orange was sprayed Image available at http://www.nrdc.org/breastmilk/diox.asp 50 25  Polychlorinated Biphenyls (PCBs) 51 Structure and Properties of PCBs Structure
An example of a PCB molecule is:
Ring C #ing similar to dioxins Properties
High chemical, thermal and biological stability
Low vapor pressure
Insoluble in water; Soluble in fatty/oily substances
Inexpensive, yet excellent electrical insulators 52 26  Uses of PCBs
Coolant-insulation fluids in transformers and capacitors
Plasticizers = agents used to make other materials more flexible
Deinking solvent for recycling newsprints
Heat-transfer fluid in machinery 53 Environmental Contamination of PCBs
From PCB-containing discarded electrical equipment
Incineration plants --- since PCBs escape as vapors
Waste discharges from capacitor manufacturing plants  Source of PCB contamination in the sediments of Hudson River
Bioaccumulated in fish and other aquatic organisms 54 27 Environmental Contamination of PCBs 55 Environmental Contamination of PCBs 56 28  Aside: Toxic Alkaloids Alkaloids are naturally-occurring complex amines, usually isolated from plants Medical uses of alkaloids
Stimulants – Ex. Caffeine, Nicotine
Analgesic – Ex. Morphine, Codeine
Tranquilizers Other properties
Addictive
Narcotics – Ex. Morphine; Heroin
Some are toxic – Coniine (cup of hemlock); Nicotine 57 Alkaloids (Cont.) Some alkaloids from nature: The opium poppy “Incisions in the seed capsules of this plant yield a milky sap. When air-dried and kneaded, the sap forms a soft material known as opium, which contains opioids, a class of alkaloids known for their pain-killing and tranquilizing effects.” Source: J. Suchocki. “Conceptual Chemistry,” Addison Wesley, San Francisco: 2001. Chapter 14 opening photograph, p. 436 58 29