Halogenated Hydrocarbons

Ecotoxicology | Halogenated Hydrocarbons

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Halogenated Hydrocarbons M A Q Khan, University of Illinois, Chicago, IL, USA S F Khan, University of Denver, Denver, CO, USA F Shattari, University of Boston, Boston, MA, USA ª 2008 Elsevier B.V. All rights reserved.

Introduction Halogenated Aliphatic Hydrocarbons Halogenated Aromatic Hydrocarbons HHCs Used in Agriculture HHCs in Polymers and By-Products Naturally Produced HHCs

Environmental Fate of HHCs Biotransformation and Biodegradation of HHCs Toxicity and Mechanisms of Toxicity of HHCs Ecotoxicology of HHCs Further Reading

Introduction

alkyl halides, namely haloalkanes, haloalkenes, and haloalkynes. Some of the unsaturated aliphatic and alicyclic HHCs are used (Table 2) as industrial solvents, others as chemical intermediates (vinyl chloride, phosgene, hexachlorocyclopentadiene, chlorohydrins, etc.) in the synthesis of other economical compounds. Still others are used in the manufacture of various important HHCs, such as chlorinated paraffins (C10 to C30 chain length), chlorofluorocarbons (banned), hexachlorobutadiene, halothane anesthetics, insecticidal aliphatic and alicyclic cyclodienes, Toxaphene, mirex, kepone, hexachlorocyclohexanes, chlorinated pyrethroids, and Chlorpyriphos. Various HHCs, especially saturated ones, are used as intermediates for nonhalogenated products (polyurethanes, polycarbonates), epichlorohydrin in resins, chlorohydrin for synthesis of propylene oxide, and for specialty chemicals, such as Grignard’s reagent, Freidel– Crafts reaction. Phosgene (COCl) is extensively used onsite – 80% in producing isocyanates and di-isocyanates for synthesis of polyurethane (>2 million metric tons yr1 globally), 10% in polycarbonate plastics (0.2 million metric tons yr1 globally). The remaining phosgene is used in other chemicals, such as herbicides, pharmaceuticals, specialty chemicals, etc. Vinyl chloride (about 12 million tons used annually in USA) is used in PVC, the most abundantly used polymer. Other products include polyvinylidene chloride and chlorobutyl rubber. Saturated HHCs are used in metal-cleaning, fire-extinguishing compounds, rubber, plastic, paint and varnish, healthcare, textile, etc., as well as in agriculture (soil fungicides, insecticides). Perfluoroacetic acids (PFAs), perfluorooctanoic acid, and perchlorooctone sulfonate have broad-spectrum industrial and consumer applications in surfactants, coatings (fabrics, upholstery, carpets, paper products), firefighting foam, and pesticides.

The United States produces about $19 billion worth of organic (petroleum-based) chemicals annually. These organic chemicals are used as intermediates in synthesis of economical chemicals, such as plastics, nylon fibers, adhesives, agrochemicals, and pharmaceuticals. Many of these synthesis processes either use chlorine or halogens directly or as intermediates, such as chlorobenzenes in the manufacture of pesticides and dyes, and vinyl chloride (12 million tons yr1 in USA) in the synthesis of polyvinyl chloride (PVC). The export of downstream products of these syntheses, such as ethylene dichloride, vinyl chloride monomer, and PVC polymer rose to 1229 million metric tons in 1995. This article identifies those economical HHCs, produced and used in the USA and abroad, which have caused and are causing ecological and human health (occupational, environmental) concerns. Hydrocarbons in which the hydrogen (forming the carbon and hydrogen bond, R?C–H) is replaced with a halogen substituent (R?C–X or RX) become chemically more stable and hydrophobic. These properties can be affected by various other factors also, such as carbon chain length and its branching, functional groups, etc. This halogenation of aliphatic (acyclic and alicyclic) and aromatic (one and more benzene rings) hydrocarbons includes a diversity of economical chemicals, used globally in amounts of millions of tons per year (Table 1).

Halogenated Aliphatic Hydrocarbons Large amounts of halogenated hydrocarbons (HHCs), including vinyl halides, are produced in massive amounts in the USA (Table 2). These HHCs can include

1832 Ecotoxicology | Halogenated Hydrocarbons Table 1 Some abundantly used HHCs and their ecosystem health and concerns

Name Aliphatic HHCs Acetyl chloride Bis(2-chloroisopropyl) ether Bis(chloromethyl) ether

Bromodichloromethane Bromoform Carbon tetrachloride

Chlorinated paraffins 2-Chloro-1,3-butadiene Chloroform

Chloromethyl methyl ether 3-Chloro-2-methyl1-propane (and allyl bromide, tetrachloroethylene) 2,39-Dichloro-1,4-dioxane 1,1-Dichloroethane

Dichloroethyl ether Dimethyl carbamoyl chloride Ethylene dichloride Hexachloro-1,3-butadiene Hexachloroethane Methyl bromide Methyl chloride

Methylene chloride

1,1,1-Trichloroethane

Uses

Effect(s)/system(s)

Human exposure

In pharmaceutical and pesticide manufacture Solvents In industry and in laboratory, an alkylating agent in the manufacture of polymers. As solvent of polymerization reactions, in the preparation of ion-exchange resin. Intermediate for organic synthesis

HS, HW SC, HS, HW, PTP SC, HS, HW, PTP

Occupational Occupational

As a solvent, flame retardant, floating agent, rubber vulcanizing, mineral separation, chemical synthesis Specialty process solvent, in semiconductors, metal recovery, cables, as a catalyst, azeotropic drying agent for wet spark plugs, soap fragrance, extracting oils As plasticizers in plastics, in paints, as metal lubricant, in adhesives, as fire retardants Manufacture of artificial rubber In synthesis of fluorochemicals and fluoro polymers, in dry cleaning, as a rubber solvent In the chemical industry for synthesis of organic chemicals Insecticidal fumigants

Rat/mouse, NMC, causes tumors in liver

Rat/mouse liver, NMC, causes tumors, SC, HW, PTP SHC, HW, PTP

AC Solvent, paints and varnish remover, in rubber cement, insecticide sprays, fire extinguishers, gasoline, high-vacuum rubber, ore-flotation, plastic and fabric spreading, produces vinyl chloride on thermal cracking AC, HW, PTP APC, HW Paints, varnish and finishing remover Solvent, intermediate in lubricants and rubber, fumigant Degreasing metals, in pyrotechnics, explosive and military In degreasing wool, sterilizing food, extracting oils An intermediate in HHCs, in silicone industry, as a methylating agent, solvent and diluent for butyl rubber, foaming agent for plastics, in thermoequipment fluids As a solvent, in paint stripping, extracting coffee and other chemicals from natural food, in manufacture of plastics, pharmaceuticals, in cleaning of metals, degreasing, in aerosols, adhesives Restricted production and use, major industrial solvent, cleaning plastic mold, cold metal cleaning, coolant, lubricant for cutting oils, solvent for dyes, cleaning agent, in textile spotting fluid

1,1,2-Trichloroethane Trichloroethylene

SC, PTP C, HW, PTP

In degreasing and dry cleaning, solvent, paint thinner, extracting caffeine, dental anesthetic, insecticide (fumigant)

CP, HS, HW, PTP C, HW, PTP CP, HW, PTP, causes tumors in liver SC, HW, PTP

SC, HW, PTP

70 000 workers exposed

C, HW, PTP

ACP, HW, PTP, causes tumors in liver CP, HS, HW, PTP, mouse liver, NMC, causes tumors in liver (Continued )

Ecotoxicology | Halogenated Hydrocarbons

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Table 1 (Continued)

Name

Uses

19,1,292-Tetrachloroethane Tetrachloroethylene

A solvent in cleaning cloths and metals, for degreasing

Vinyl cyclohexene dioxide Vinylidene chloride Vinyl chloride

Synthesis of PVC

Aromatic HHCs Benzoyl chloride Benzyl chloride

CCIU Chlorambem

Chlorambucil Chlorobenzenes Chloronaphthalenes Chloroprene Dichlorobenzene Epichlorohydrin Hexachlorobenzene

Hexachlorophene

Textile and dye industries as a fastness compound Intermediate in benzoil compounds (benzal chloride, benzyl alcohol, and benzaldehyde), manufacture of quaternary ammonium chloride, plastics, dyes, synthetic tannins, pharmaceuticals, perfumes, and resins Formulation or application of this pre-emergence herbicide Drug against cancer In synthesis of chloroanilide herbicides, bacteriocides Heat transformer media, solvents, lubricant, dielectric fluid, electric insulation In the production of artificial rubber Intermediate in polyphenylene insecticide for termites (fumigant), disinfectant Fungicide, intermediate for dye and hexafluorobenzene, synthetic rubber, plasticizer in PVC, military pyrotechnic, electrodes Topical anti-infective agent, detergent, antibacterial soaps, surgical scrubs, hospital equipment, fungicide

Lindane Monochlorobenzene

Effect(s)/system(s) CP, HW, PTP CP, HW, PTP, causes tumors in liver AC C, HS, HW, PTP HC, HW, PTP

AC, HS, HW

C, HS, HW, PTP CP

HC, AC, HS

C

In synthesis of nitrochlorobenzene as a dye intermediate, solvent APC AC, HS, HW, PTP, rat/ mouse liver, NMC C, HS APC, HW CP AC, HW, PTP, rat liver, lungs, NMC Heat transformer media, transformer fluid, and solvent

Pesticides Aldrin

Pesticide manufacture, formulator and applicators

C, HS, HW, PTP

In the manufacture of epichlorophydrin and glycerol Processing or formulating pesticides, control rootborers on bananas, wireworm control in tobacco and ants

HS C, HS, HW

Chloronaphazine DDT DDVP

2500 workers

APC, HS, HW C

Trichlorobenzene

Chlorobenzilate p-Chlorobenzotrichloride Chlorodane

Workers involved in the manufacture

C(N,P), HS, HW, PTP, mouse liver, NMC

O-Nitrochlorobenzene P-Nitrochlorobenzene PCBs (polychlorinated biphenyls) P-Chlorobenzyl chloride Pentachloronitrobenzene Picloram TCDD

Allyl chloride Chlordecone

Human exposure

Pesticide manufacture Broad-spectrum insecticide for homes, gardens, and soil insects Treatment of leukemia and related cancer

In air, water, and food 5000 workers 600 workers

Rat liver, NMC AC CP, HS, HW HC, HS ASC, HS, HW, PTP C, HS, HW, PTP (Continued )

1834 Ecotoxicology | Halogenated Hydrocarbons Table 1 (Continued)

Name

Uses

1,2-Dibromo3-chloropropane 1,2-Dibromoethane

3,39-Dichlorobenzidine and salts P, P9-Dichlorodiphenyl 1,2-Dichloroethane

Dichloroethylene Dieldrin HCB HHC (hexachlorocyclohexane) Heptachlore 4,49-Methylenebis(2-chloroaniline) Mirex Phenazopyridine hydrochloride 2,4,5-T TDE Toxaphene Trichlorophenyl

Effect(s)/system(s)

Human exposure

Stomach, mammary gland Subcutaneous, stomach, blood vessels, lungs AC, HW, PTP

Subcutaneous, stomach, blood vessels, mammary gland Mouse liver, NMC Mouse liver, NMC C, HW, PTP C, HW, PTP C, HS, HW, PTP C, HW C, HS, HW C C, HS, HW C, HW, PTP C, HS, HW, PTP SC, HW, HS, PTP

C, human carcinogen; AC, animal carcinogen; SC, suspected human carcinogen, PTP, USEPA’s toxicity priority pollutant; HW, hazardous waste (USEPA).

Halogenated Aromatic Hydrocarbons Some of the commonly used aromatic HHCs include chlorinated benzenes, benzyl chloride, chlorinated phenols, chlorinated pyridines, chlorinated naphthalenes, chlorinated biphenyls, chlorinated dibenzodioxins, chlorinated dibenzofurans, chlorinated terphenyls, chlorinated benzoyl toluene, chlorinated phenoxyacetic acids, chlorobutyl rubber, Grignard’s reagent, Friedel–Crafts’s reagent, Diels–Alder Reaction, and alkanolamine. Monochlorobenzene, dichlorobenzene (m- and p-dichlorobenzenes), trichlorobenzenes (1,2,3-, 1,3,5-, and 1,2,4trichlorobenzenes), and their derivatives (1-chloro-3-nitrobenzene, 1-bromo-4-chlorobenzene) have been widely used as chemical intermediates and solvents. p-Dichlorobenzene is used as a fumigant (insecticide) and disinfectant. A mixture of trichlorobenzene isomers is used in termite control. 1,2,3and 1,3,5-trichlorobenzenes have been used as heat-transfer media, transformer fluids, and solvents. Hexachlorobenzene (HCB) is used as a fungicide and as an intermediate for dyes and hexafluorobenzene, synthetic rubber, PVC, an additive for military’s pyrotechnique compositors, and as a porositycontrolling agent in manufacture of electrodes. Benzoyl chloride is an intermediate in the synthesis of benzyl compounds, quaternary ammonium chloride, dyes, tanning materials, pharmaceuticals, and perfume

preparation. It is used in the textile and dyes industries as a fastness improver for dyed fiber and fabrics. Hexachlorophene is a topical anti-infective agent, used in detergents and as an antibacterial agent for soaps, surgical scrubs, hospital equipment, cosmetics, etc. It is used as a fungicide for vegetables and ornamental crops. Benzethonium chloride is used as a topical anti-infective agent in medicine and as a germicide for cleansing food and dairy utensils, and as a controlling agent for removing pool algae. It is an additive in deodorants and hairdressing preparations. Tri-, tetra-, penta-, hexa-, and octachloronaphthalenes have been formerly used in heattransfer media, solvents, lubricant additives, dielectric fluids, and electric insulating material. In addition to the agrochemicals, a few other HHCs that have caused most serious ecotoxicological and health effects include polychlorinated biphenyls (PCBs), polybrominated biphenyls (PBBs), chlorinated naphthalenes, terphenyls, dioxins, dibenzofurans, and diphenyl ethers. PCBs are mixtures of various congeners/isomers (Table 3). Mixtures of various congeners are marketed as Aroclors (Clophen outside USA) in which the last two digits indicate the degree of chlorination, such as Arochlor 1254 and 1260 (and Clophen A 60) (Table 4). These are chemically stable, unreactive, viscous liquids of low volatility. These have been used in closed, semiclosed, and

Ecotoxicology | Halogenated Hydrocarbons Table 2 HHC production in USA Million metric tons yr1a Chemical

Current

Past

Vinyl chloride Solvents Methyl chloride Methyl bromide Chloroethanes 1,2-Dichloroethane 1,2-Dibromoethane 1,1,1-Trichloroethane Hexachloroethane Ethylene dichloride Ethylene dibromide Trichloroethylene Tetrachloroethylene Carbon tetrachloride Chloroform

6–12 (10)

0.599 (694 in 1978) 0.198 (1971) 0.036 (1975)

2.1 0.3 >1.0

0.3 0.7 0.5 0.3

Other halogens Chlorobenzene p-Chloronitrobenzene o-Chloronitrobenzene Dichlorodifluoromethane Trichlorofluoromethane Chlorinated paraffins Hexachlorocyclopentadiene Total Pesticides Herbicides 2,4-D 2,4,5-T Propachlor Insecticides Silvex Methoxychlor Chloropicrin Toxaphene DDT Cyclodienes Aldrin/Dieldrin Ethylene dibromide Chloral Alachlor Fungicides Trifluralin PCP HCB

11 (1978) 0.230 (1978) 0.644 (1978) 0.228 0.016 (1980) 0.008 5 (1980) 0.299 (1978) 0.725 (1978) 0.737 (1978) 0.349 (1978) 0.240 (1967) 0.050 (1967) 0.017 (1967) 0.083 (1967) 0.120 (1967) 0.028 (1967) 0.050 (1967) 1.388 (1.0) 0.674 0.044 (1970) 0.012 (1970) 0.011

0.28

PCBs USA Rest of the world

0.013

Chlorofluorocarbons

0.12

0.002 (1970) 0.005 5 (1975) 0.005 7 (1975) 0.31 0.059 (1970) 0.89 (1975) 0.009 0.088 (1975) 0.026 (1967) 0.089 (1976) 0.143 0.028 0.040 (1975)

900 (1978) 1000 (1978)

a

Data from Anonymous (1979) Environmental Quality. The Annual Report of Council on Environmental Quality, 816pp. Washington, DC: US Government Printing Office.

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Table 3 Numbers of possible congeners (isomers) of halogenated aromatics Halogen substitution

Benzenes

Dioxin

Furans

Mono Di Tri Tetra Penta Hexa Hepta Octa Nona Deca

1 3 4 3 1 1

2 10 14 22 14 10 2 1 0 0

4 16 28 38 28 16 4 1 0 0

Total

13

75

135

Biphenyls 3 12 24 42 46 42 24 12 3 1 209–265

oils, carbonless copying paper, wall coatings, surface treatment in textiles, wood, metal, and concrete; in caulking material, impregnated fruit wrappings, cutting oils, microscopic mounting and immersion oil, vapor suppressants; in insecticide and bactriocide formulations, etc., from agriculture to office buildings, automobiles, and homes. PCBs have caused widespread contamination. However, major environmental sources of PCBs include manufacturing wastes, careless disposition, and dumping. From 1929 to the mid1970s, USA produced 1.4 billion tons of PCBs and rest of the world about the same amount. In USA about 300 000 t of PCBs have been disposed in dumps and landfills; and about 60 000 t in fresh water and coastal waters, while air contains less than 30 000 t of PCBs. The worst contamination with PCBs in USA occurred in Escamba Bay, FL; Lake Michigan, IL; the Ohio River, OH; Francisco Bay, CA; the Hudson River, NJ; and Puget Sound, WA (Table 5). PBBs have been used mostly as flame retardants and have caused only local problems based on accidental contamination of cattle feed and waste disposition in Michigan. The brominated hydrocarbon flame retardant hexabromocyclododecane (HBCD) is blended with textile and polystyrene foam. It can leach out from these products and contaminate water and biota. Flame retardants bromodiphenyl ethers have become common environment and human contaminants. Polychlorinated dioxins (PCDDs) and dibenzofurans (PCDFs) are present in halogenated aromatics as contaminants or are produced during their synthesis or incineration. Some of these are persistent and extremely toxic to wildlife, including higher animals and humans.

HHCs Used in Agriculture ‘open-end’ systems, such as hydraulic fluids, coolants, electric transformers, capacitors, insulations (electric wire and cable), heat-transfer systems, fluorescent light ballasts, lubricating oils, plasticizers, paints, inks, paper, dielectric fluids, heat-transformer fluids, lubricants, vacuum pump

HHC agrochemicals include insecticides, fungicides, and herbicides (Table 2). Dichlorodiphenyltrichloroethane (DDT) and its derivatives (dichlorodiphenyldichloroethylene (DDE), dichlorodiphenyldichloroethane (DDD),

1836 Ecotoxicology | Halogenated Hydrocarbons Table 4 Percentage of various congeners in commercial PCB mixtures Compound

Dichloro

Trichloro

Tetrachloro

Pentachloro

Hexachloro

Heptachloro

Octachloro

Arochlor-1242 Ar-1254 Ar-1260

16 0.5 ND

49 1 <0.5

29 21 1.5

8 48 12

1 23 38

0.1 6 41

ND ND 8

Table 5 Sites with high levels of HHC HHC

Site

Animal contaminants

PCB

Lake Michigan (Waukegan Harbor) Great Lakesa

Fish, birds, human

St. Lawrence Seawaya New York (Hudson R.)

TCDD

Wisconsin (Sheboygan R.) Italy (Sveso)

Kepone

Maryland (James R.) Maryland (Chesapeake Bay)

Fish, piscivorous birds Fish, whales Fish, birds, marine animals Fish, birds Wildlife, livestock, humans Wildlife Invertebrates, fish, wildlife

a

DDT, DDE, and dieldrin also present.

Kelthane, methoxychlor), cyclodienes (dieldrin, chlordanes, heptachlor, endrin, mirex, kepone), endosulfans, hexachlorocyclohexanes, ethylene dibromide, methyl chloride, Abate, and Chlorpyrifos are/have been most abundantly and indiscriminately used as residual insecticides and are/have been causing ecological and health problems. Cyclodienes were banned in the 1970s and Toxaphene and mirex in the 1980s. Only a few of these insecticides are allowed a restricted use because of their health and ecological effects. However, these (especially DDT) may still be used in developing countries (mosquito control in Africa) as well as in public health and military for control of arthropod vectors and body lice. Chlorinated phenols (especially PCPs) were more commonly used in lumbar treatment. Bleaching of pulp with chlorine can produce chlorophenols, polychlorinated dibenzodioxins (PCDDs), and polychlorinated dibenzofurans (PCDFs). Chlorophenols are acidic, water soluble, chemically reactive, but have limited persistence. Chlorophenoxy herbicides are used to control broadleaf weeds (dicotyledons). These derivatives of phenoxyalkane carboxylic acids (2,4-D, 2,4,5-T, (4-chloro-2-methyl-phenoxy)acetic acid (MCPA), 2,4-DB) are water soluble as alkali salts and lipophilic as esters. These are readily biodegradable. These are of concern because of phytotoxicity, but mostly because of the serious ecological and health effects of their contaminant PCDDs, especially 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

PCDDs are flat molecules with varying substituents of chlorine resulting in 75 possible congeners (Table 3). These are chemically stable and highly lipophilic with limited solubility in organic solvents. These are not commercial products and exist as by-products formed during synthesis of chlorinated phenols, as well as during the incineration of chlorinated aromatics and dispersion of chlorophenols. The most toxic PCDD is TCDD. Chlorinated anilide herbicides, such as propanil, have been shown to be contaminated with extremely toxic tetrachlorazo- and tetrachloroazoxy-benzenes. The latter can also be produced on microbial degradation of these herbicides.

HHCs in Polymers and By-Products PVC, one of the most versatile thermoplastics, accounts for 28% of the global annual chlorine consumption (19 million tons PVC). By-products, such as 1,1,2-trichloroethane, and gaseous and liquid wastes on incineration/ oxidation are sources of concern. PVC accounts for 150 000 t yr1 of global production. Other end products using HHC include Neoprene or chlorobutyl rubber. Chlorohydrins are used in the production of propylene oxide to manufacture propylene oxide polymers. It is also used in synthesis of epichlorohydrin for resins and polymers, and specialty chemicals (alkanolamines). Other polymers include nylon-6, 6-hexamethylenediamine for carpeting, etc., and fluoropolymers (50 000 t yr1, globally), and Silicone (400 000 t yr1, globally).

Naturally Produced HHCs About 1500 different HHCs, from simple alkanes to complex polyhalogenates, are produced naturally by a diversity of aquatic and terrestrial organisms in microgram per kilogram body mass levels. Methyl chloride, methyl iodide, and carbon tetrachloride, which are animal carcinogens, occur naturally in marine environment. Several of those produced in large amounts include chloromethanes, chlorophenols, and chlorinated humic/fulvic compounds. Largest amounts of these HHCs are produced in soil and sediments. Some of these HHCs include haloperoxidase enzymes, which yield volatile

Ecotoxicology | Halogenated Hydrocarbons

and phenolics. Reactions of chlorine with lignin pulp and humic/fulvic acids produce chloroliginin. Numerous other halogenated hydrocarbons, many structurally similar to known animal carcinogens and toxicants, occur in both terrestrial and marine organisms. Several halogenated hydrocarbons are essential for normal functioning of living organisms.

Environmental Fate of HHCs Aliphatic HHCs are used mostly as solvents, and their production, use, and disposal can pose ecological and health (environmental and occupational) problems. Chlorination of drinking water produces chloroform and carbon tetrachloride, which, in USA alone, can continuously expose 29 million humans including infants and children. Tri- and tetrachloroethylenes used in dry cleaning are common environmental contaminants, especially at hazardous waste sites. These are present in groundwater and ambient and indoor air as well as in drinking water. Highly stable perfluoroalkyl acids, perfluorooctanoic acids, and perfluorooctane sulfone are present in environment, wildlife, and humans. Aromatic HHCs have a wide range of physical properties, which determine their environmental fate and effects. These HHCs range widely in their distribution in different environmental compartments and phases, some of which is related with differences in their persistence. Low molecular weight HHCs are more volatile than higher molecular weight HHCs and can be present in occupational, urban, and industrial air. The major reactions during their transport in air involve hydroxyl radical and photolysis. Estimates of sources of HHCs and of their concentrations can be more accurately predicted by using quantitative structure–activity relationship (QSAR) models. For example, the inputs of carbon tetrachloride in the troposphere should be 1–2 million tons while anthrapogenic sources amount to only one-tenth of this. Environmetal sources of mono-, di-, and trichloroacetic acids are not fully known. Some of these can be biological and environmental products of perfluorooctanoic acids. These are present globally in ppb (mg l1) concentrations in rain and surface water, which are greater than any other low molecular weight HHC. Trends in release of HHCs and by-products at manufacturing sites are more effectively controlled now and this has reduced their emissions and disposition. There is a dramatic reduction in PCDDs, PCDFs, and chlorophenol discharges from the paper and pulp industry due to the new delignification and bleaching technologies. Legislative restrictions and new technologies have also reduced emissions of PCDDs/PCDFs from waste incineration plants. HHC pesticide usage has declined

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Table 6 Biological concentration of HHC in biota Bioaccumulation:  in water HHC

Algae

Fish

PCP 2,4,6-TCP HCB 2,4,29,49-Pentachlorobiphenyl 2,5,4-Trichlorobiphenyl 2,29-Dichlorobiphenyl Pentachloronitrobenzene Hexachlorocyclopentadiene 2,4-D p-Chlorobenzoic acid 2,4-DCBA

1 240 800 24 000 11 500 7 700 3 050 3 600 1 140 6 63 0.9

350 230 400 770 650 830 380 308 2 1.1 0.3

tremendously. However, nonbiodegradable mirex is now distributed all over North America. Kepone had contaminated James River, VA. In the 1970s, the usage of these insecticides was minimized and most of these were banned by 1980. Volatility and lipophilicity of polychlorinated aromatics (PCB, PCDD, PCDF, etc.) are associated with the degree of chlorination. Chlorination increases lipophilicity but also reduces volatility. Thus, low concentrations of HHCs, especially less chlorinated ones, are present in surface waters, while highly chlorinated aromatics remain in sediments and are picked up by invertebrates in high concentrations, as has been reported for 4-, 5-, and 6-chlorinated congeners of PCBs. In surface waters, photolytic ortho-dechlorination is common. The octanol:water partition coefficients for PCB 101, 128, 136, and 1 are 2.5, 5, 10, and 0.002, respectively. Bioconcentration factors for these chlorinated aromatics relate with their partition coefficients (Table 6).

Biotransformation and Biodegradation of HHCs Dichloromethane is metabolized to CO and HCHO (carcinogen). The metabolites of trihalomethanes start with loss of halide (via P4502E1), leading to CO production. Covalent bonding to macromolecules occurs via phosgene in case of chloroform and via dibromocarbonyl in the case of bromoform. Chloroform is metabolized to reactive phosgene, and carbon tetrachloride forms trichloromethyl, trichloromethylperoxy, and chlorine-free radicals. Several haloalkanes are first conjugated with GSH in liver and then metabolized to cysteine conjugates in kidney. The latter conjugates are converted, by -lyase, to episulfonium ions.

1838 Ecotoxicology | Halogenated Hydrocarbons

Metabolism of haloethylenes (trichloroethylene, perchloroethylene, vinyl chloride, vinyl bromide, vinyl fluoride, vinylidene chloride, vinylidene fluoride) starts with epoxidation (by P4502E1). Resulting oxiranes are highly reactive and bind covalently to nucleic acids. Chlorinated ethylene epoxides breakdown as a function of halogenated substituents on the carbon. Compared to ethylene oxide, vinyl chloride and vinylidene chloride with increasing chlorination show an increase in bond strength of the chlorinated carbon to the oxygen and a decrease in the bond strength to nonchlorinated carbon. When each carbon is substituted with single chlorine, the C–O bonds become equally stable. When there are two chlorines on one carbon and one on the other, there is, again, a weakening of the less chlorinated C–O bond. The asymmetrical chloroethylene is more carcinogenic than symmetrical ones because of the bond breakage, which potentiates covalent bonding to DNA. There are limits to the effectiveness of highly reactive species, for example, the weak carcinogenic activity of vinyl chloride may be due to the instability of its putative metabolite (1,1-dichloroxirane), which is likely to be degraded rapidly. The less reactive oxiranes bind to DNA more readily and stably. Trichloro- and tetrachloroethylenes are metabolized to monochloroacetic acid and trichloroacetic acid, which are excreted as such or as their glucuronides and alcohols. The environmental fate of most aromatic HHCs is determined by halogen substituents and the types of organisms exposed to them. The position of chlorination is more important than the degree of chlorination in biotransformation and degradation. Chlorination of biphenyls at ortho-position causes steric hindrance and decreases the degree of coplanarity at 2,29,6,69. Chlorinated dioxins and furans are held in coplanar orientation by the oxygen bridge. Aerobic bacterial degradation of PCBs involves dechlorination at o- and m-positions. In sediments, bacterial dechlorination is inversely proportional to their lipophilicity. In soils and sediments, biodegradation, hydrolysis, and photolysis determine their fate. The dechlorinated products can be attacked by bacterial deoxygenases as well as by animal P450 oxygenases. Animal metabolism of polychlorinated aromatics starts with attack by P450 monooxygenases causing hydroxylation (addition plus keto–enol rearrangement) via epoxidation, with or without displacement of the chlorine (NIH shift). Vinyl halogens favor epoxidation. PCBs with 4,49 and/or 3,39,5,59-chlorination are refractory to biotransformation, while PCBs with four or more chlorines but with hydrogen in either 4 and/or in 4,59-positions of one or both rings are readily metabolized. Polyhalogenated aromatics induce P450 monoxygenases; coplanar PCBs and TCDD induce P4501A1 while noncoplanars induce P4502B isozymic forms. P4501A1 can oxidize coplanar

PCBs readily while P4502B preferentially oxidizes o-substituted congeners. Resulting hydroxylated metabolites can be conjugated with glucuronic acid and/or glutathione, which are excreted in bile; but glutathione conjugates are re-absorbed or metabolized to meracaptans, which are excreted as mercapturic acid or form corresponding sulfhydryl and methylated products. The methyl-thio-PCB can be further oxidized to corresponding sulfoxides and sulfones, which may be retained in tissues. The methylsulfonyl metabolites of PCBs, HCB, and DDT show high tissue-specific binding and toxic effects. Similar hydroxylations and dechlorinations and/or NIH shifts occur in dioxins and furans. The dihydroxy products following p-oxidation can also lead to ring opening and reduction of furans, which reduces their toxicity.

Toxicity and Mechanisms of Toxicity of HHCs HHCs exert specific or broad-spectrum effects on living organisms. They can be acutely lethal or exert subchronic and chronic toxic effects, such as developmental (teratogenic), hormonal (endocrine disruptors), carcinogenic, neurotoxic, immunotoxic, and neurobehavioral effects. Haloethylenes undergo epoxidation by P4502E1 and form oxiranes depending on halogen substituents, which are highly reactive and bind covalently to DNA. Compared to ethylene oxide, vinyl chloride and vinylidene chloride, with increasing chlorination, show an increase in bond strength of the chlorinated carbon to the oxygen and a decrease in the bond strength to nonchlorinated carbon. The asymmetric chloroethylenes are more carcinogenic than symmetrical ones because the bond breakage potentiates covalent bonding to DNA. There are limits to the effectiveness of highly reactive species, for example, weak carcinogenic activity of vinyl chloride may be due to instability of its putative metabolite (1,1-dichloroxirane), which is likely to be degraded rapidly. The less reactive oxiranes are more DNA binding. Glutathione conjugates of several haloalkanes in liver are converted to cysteine conjugates in kidney, where their episulfonium ions bind covalently to DNA and proteins leading to nephrotoxicity and carcinogenicity. Vinyl chloride and bromide are genotoxic and carcinogenic. Trichloroethylene is not carcinogenic in liver while vinylidene chloride is. Dichloromethane is a central nervous system (CNS) depressant and may even suppress normal inspiration via this route. It is metabolized to CO, which forms COHb and HCHO (which can react with DNA). Chloroform affects liver and causes renal epithelial tumors. Its metabolite phosgene covalently binds to liver proteins and depletes hepatocyte GSH. Carbon tetrachloride forms trichloromethyl, trichloromethylperoxy,

Ecotoxicology | Halogenated Hydrocarbons

and chlorine-free radicals, which can attack unsaturated bonds of fatty acids in the endoplasmic reticulum leading to lipid peroxidation and membrane damage. It causes centrilobular necrosis and fatty liver. In experimental mammals, HHCs that cause fatty liver without necrosis include chlorobromomethane, dichloromethane, cis-1,2-dichloroethylene, tetrachloroethylene, and 2-chloroethylene. Those HHCs which cause fatty liver and necrosis include carbon tetrachloride, carbon tetraiodide, carbon tetrabromide, bromotrichloromethane, chloroform, iodoform, bromoform, 1,1,2,2-tetrachloroethane, 1,2-dichloroethane, 1,2-dichloromethane, 1,1,1-trichloroethane, 1,1,2-trichloroethylene, 2-chloro-n-propane, and 1,2-dichloro-p-propane. Those HHCs which cause no liver hypertrophy but only necrosis are methylene chloride, methyl bromide, methyl iodide, dichlorodifluoromethane, trans-1,2-dichloroethylene, ethylene chloride, ethyl bromide, ethyl iodide, and n-butylchloride. Aliphatic HHC insecticides can be neurotoxic (which inhibit GABA-A1 chloride ion channels in brain and ATP-ases in axons), respiratory poisons, endocrine disruptors, teratogens, carcinogens, etc. Some of these HHCs can cause liver enlargment and induction of cytochrome P-450 isozymic forms, mostly P4502B. Aromatic halogens and polyaromatic HHCs also cause hepatic hypertrophy and induction of P450 isozymes, both P4501A and 2B. This induction of P4501A is mediated via transport of these HHCs by cytosolic Ah receptor (AHR, a member of the basic-helix-loop-helix/ per, ARNT/AHR, SIM homology (bHLH/PAS) protein) inside the nucleus where heterodimer ARNT (Ah-receptor nuclear translocator) binds to specific nucleotide recognition sequence on regulatory region of the target gene DNA (dioxin response element, DRE). This leads to altered gene expression and results in hepatotoxicity, carcinogenicity, teratogenicity, etc. These and other responses are highly tissue, sex, age, and species specific. Differences in ARNT domain may be responsible for differential gene expression and altered sensitivities of strains and species, as well as to differences in genomic sequence at promoter and enhancer region. The gene expression of AHR and ARNT during embryonic development is stage and tissue specific. AHR mRNA appears in fetal mouse tissue between gestation days (GDs) 10 and 16. In DRE–lacZ mouse model, AHR is present in several developing tissues including genital tubercle, palate, and paws. In a transgenic mice model, the TCDD exposure in utero at GD 14.5 induced lacZ expression in the mesenchymal epithelium of developing paws and alteration in gene expression profile were observed after 24 h. In liver cells of rats exposed subchronically for 13 weeks to AHR agonists TCDD (toxicity equivalent factor, TEF ¼ 1), pentachlorobenzofuran (TEF ¼ 0.5), 3,39,4,49,5pentachlorobiphenyl (TEF ¼ 0.1) several genes exhibited altered expression. Out of these genes, Serpia 7 (27-fold),

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Cyp3a13 (1000-fold), and Ces3 (fivefold) were downregulated. PCB126 and 153 had no effects but their mixture mimicked TCDD downregulation of 11 genes. Genderand species-specific repression occurred within this subset of genes. In AHR knockout mice, seven of the 11 genes were downregulated. This early downregulation is followed by upregulation and liver carcinogenesis. In utero exposure of mice to TCDD upregulates amphiregulin (one of the epidermal growth factor signaling ligand) gene expression in fetal ureter. In mice, disruption of AHR signaling by TCDD decreases body weight and fecundity, and causes liver defects and disruption of cardiac and vascular development. The -, / -, and -isoforms of the nuclear hormone receptor superfamily of ligand-activated transcription factors (peroxisome proliferator activated receptors) respond to perfluorooctanoic acid and perfluorooctane sulfonate (in vivo and in utero) and alter gene expression in various tissues during development and in adults leading to developmental toxicity and other adverse effects. Tetrachloroazo- and tetrachloroazoxybenzenes inhibit adrenocorticotropic hormone release and affect thymus and other lymphatic systems. Toxic potency of congeners of polychlorinated aromatics is usually compared with that of TCDD and expressed as ‘dioxin equivalent factor’. DEF depends on the coplanarity and chlorination in paraand meta-positions. The net toxicity of the PCB mixtures depends on these coplanar congeners, whose concentration in most commercial mixtures is very low. The DEF is reflective of the affinity of the congener for the cytosolic AHR causing its activation. The increased synthesis of the CYPIA1 gene product P4501A1 increases the catalysis (hydroxylation) of coplanar HHCs. The interaction of HHCs with AHR initiates a constellation of effects, such as thymic atrophy, hypo- and/or hypertrophy of liver, chloracne, wasting, teratogenesis, etc. TCDD is 40–400 times more potent than other halogenated aromatics in binding with AHR. The non-AHR-type effects include hepatomegaly, induction of Phase II enzymes, and porphyria. However, the acute lethality of TCDD and other halogenated aromatics is dependent on species. In the case of PCBs, the confromational restrictions and hydroxylations are important in their estrogenic activity. Porpyhria-related diseases are species specific and frequently slow to develop. These polyhalogenated aromatics and their metabolites are, also, potent inducers of -aminolevolunic acid synthase, the rate-limiting enzyme of porphyrin synthesis.

Ecotoxicology of HHCs Factors that affect toxicity of individual HHCs are increasing numbers of halogens in the molecule, increasing the size of the molecule, increasing ease of homolytic

1840 Ecotoxicology | Halogenated Hydrocarbons

cleavage, electronegativity of halogens, and/or their chain length. Differences in closely related compounds, such as positional isomers (Table 8) and functional groups, have pronounced effects on ecodisposition, bioconcentration, biodispersion, and biological effects. These major differences within subsets of generic properties are important in understanding the ecotoxicology of HHCs. The relation between structure, metabolism, and toxic action for one subgroup of HHCs may not be duplicatable in other groups. So caution must be taken in conclusively generalizing from experimental deductions.

Bioconcentration Most of the serious ecological problems caused by HHCs are related with bioaccumulation and bioconcentration via food chain. For example, DDT, dieldrin, PCBs, etc., at their parts per trillion concentrations in water can be found in top carnivores in parts per million (ppm) concentrations, more than a millionfold ecological concentration. For example, terns in Lake Michigan can have 26 ppm in their fat and their eggs can have up to 100 ppm PCBs.

Effects on Aquatic Wildlife The bodies of water close to industrial, agricultural, and urban centers show high levels of HHCs in water, sediments, and biota. Even in Arctic and Antarctic residues of PBBs, chlorobornanes, PBDEs, PCN, PCBs, and DDT can be detected in water and biota. Embryos and young animals are generally more sensitive to HHCs and other toxicants. Bioconcentration of these stable compounds can lead to high concentrations in organisms higher up in the food chain. Each level of organisms may be affected by chronic exposures to these halogens. However, the effects on lower organisms are not easily available and recorded. HHCs differ widely in their toxicities to aquatic food chain organisms as exemplified by water flea Daphnia magna (Table 7). Fish, amphibians, and reptiles

Tumors in English sole (Puget Sound, WA), Medeka, and other species may be due to their exposure to HHCs along with polycyclic aryl hydrocarbons (PAHs). In addition to this, mortality of hatchlings (fry), adult survival, and reproductive effects (feminization) may occur. The decline in frog populations and their hind leg and other deformities have been assumed to be related with HHC pesticides. Alligators exposed to DDE and PCBs have been reported to show atrophy of their testes causing lowering of testosterone and feminization.

Table 7 A list of commonly used halogenated hydrocarbons and their toxicities to D. magnaa HHC Alkanes Methyl chloride Methyl bromide, methyl iodide 1,2-Dichloromethane Ethyl iodide, ethyl bromide 1,1-Dichloropropane 1,2-Dichloropropane 1,3-Dichloropropane n-Butyl chloride Vinyl chloride Vinyl bromide 2-Chloro-n-propane 1,2-Dichloro-p-propane Chlorobromomethane Trichloromethane 1,1,2-Trichloroethane 1,1,1-Trichloroethane Hexafluoropropane Tetrachloromethane Tetraiodomethane Dichlorofluoromethane 1,1,1,2-Tetrachloroethane 1,1,2,2-Tetrachloroethane 1,1,2,2,2-Pentachloroethane Hexachloroethane Alkenes 1,3-Dichloropropene Tetrachloroethene Vinylidene chloride Hexachloropropene Alkynes 1,1-Dichloroethylene trans-1, 2-Dichloroethylene 1,1,2-Trichloroethylene Methylene chloride Tetrachloroethylene cis-1,2-Dichloroethylene 1,1,2-Trichloroethylene Monohaloethylenes Tetrafluoromethylene Chlorotrifluoromethylene 1,1-Dichloro-2,2-difluoroethylene Chlorotrifluoroethylene 2-Chloroethanol 2,2,2-Trichloroethanol Halogenated aromatics Chlorobenzene 1,2-Dichlorobenzene 1,4-Dichlorobenzene 1,3-Dichlorobenzene 1,2,4-Trichlorobenzene 1,2,5-Tetrachlorobenzene Pentachlorobenzene Chlorinated phenols 2-Chlororophenol 4-Chlorophenol 3-Chlorobiphenyl 2-Chlorobiphenyl 2,4-Dichlorophenol

LC50 (g l1)

363 23 52 280

198 70 530 35

24 41 12 0.006 6 14

135 220 51

17 0.042 0.088 2.07 1.88 9.7 5.3 5.24 4.89 5.30 0.43 0.26 (Continued )

Ecotoxicology | Halogenated Hydrocarbons Table 7 (Continued) HHC 3,4,5-Trichlorophenol 2,4,6-Trichlorophenol 2,4,5-Trichlorophenol 2,3,4,6-Tetrachlorophenol Tetrachlorophenol 2,4,5,6-Tetrachlorophenol Pentachlorophenol Pentachlorophenol-sodium Hexachloro-1, 3-butadiene Hexachlorocyclopentadiene Pesticides Dichlorovos 2,4-Dichlorophenoxyacetate Picloram Trichloropropane Chloramp Chloroxuron Lindane Dibenzofuran DDT Chloropheniphos Endosulfan Permethrin

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Table 8 Oral toxicity of TCDD in mammals LC50 (g l1) 0.68 3.03 2.70 0.29 0.41 0.56 0.73 0.40

0.004 0.83 59 0.117 212 2.95 0.899 0.005 0.003 0.043 0.283 0.002

a Data from Adams WJ, Champan GA, and Landis WG (eds.) (1988) Aquatic Toxicology and Hazard Assessment, Vol. 10. 579pp. Philadelphia: ASTM.

Water birds

Residues of HHCs in food and water of water birds has contaminated and affected fish-eating birds’ reproduction (feminization of males, nest abandonment, ineffective incubation). This has been observed in Great Lakes Region in cormorants, terns, raptors, and other species, and in local and migratory waterfowl in Lake Michigan, Green Bay, Long Island Sound as well as in Adeline penguins and south polar skua. In Lake Michigan Basin, hatchling failure and malformations and sex reversal in male double-crested cormorants have been noticed. Foster tern eggs contain very high levels of PCBs leading to embryotoxicity, aberrant parental behavior, and hormonal changes. High concentration of DDT, dieldrin, and PCBs dangerously reduced the number of raptors in North America and Britain and seriously affected their reproduction in the Great Lakes region.

LD50 (g kg1 body wt.) Animal

Average of male and female

Guinea pigs Rat Mice Rabbit Monkey Hamster

0.6–2.1 22–45 283 115 50–70 100

LD50 values (mg kg1) for male rats for DDT, dieldrin, Toxaphene, dichlorovos, and lindane are 113, 46, 90, 80, and 200, respectively. Data from Kimbrough RD (1981) Chronic toxicity of halogenated biphenyls and related compounds in animals and health effects. In: Khan MAQ and Stanton RH (eds.) Toxicology of Halogenated Hydrocarbons, pp. 23–37. New York: Pergamon.

high concentrations of DDT and its metabolites showed pathological changes in their uteri. Those with high PCBs had implantation failure and adrenal cortex atrophy. California sea lions have also shown reproductive disorders (premature birth), immune suppression, gastric and intestinal ulceration, and liver, skin, and kidney lesions, which are also seen in adult beluga whales. Land mammals

In Michigan, mink and ferret populations fed PBB/ PCB-contaminated lake fish showed reproductive failure, induction of P450 in hepatocytes, degenerative renal changes, anorexia, gastric ulcers, loss of hair, and enlargement of liver, pancreas, and adrenals. The toxicities of various HHCs to experimental mammals (Table 8) indicate the severity of TCDD and its related coplanar chlorinated aryl hydrocarbons. Species-specific differences in sensitivity to these HHCs are very prominent (Table 9). In rats, dietary intake of PCBs for 130 days showed no symptoms at 0.001 mg kg1 d1 (¼0.13 mg kg1), but a 10 times higher dose reduced fertility in two to three generations and a 100 times higher dose affected neonatal survival. A 2-year dietary exposure (0.1 mg kg1 d1) of rats caused several chronic effects, such as wasting, fatty liver, lung lesions, hypothyroidism, chloracne, liver cancer, and mortality.

Sea mammals

In St. Lawrence Seaway, whales/seals contain high concentrations of PCBs and PAHs, which are high in sediments: concentrations of PCB (180 ppm) in male belugas and in blubber of young ones (270 ppb) (young ones showing metastasized bladder carcinoma and males with other tumors). Juvenile females had about 600 ppm PCB in blubber. Mink whales from the Antarctic contained PCBs, HHCs, HCB, and DDT in blubber and food. Baltic seals are also contaminated with PCBs and DDT. Females with

Humans

While adult humans can be exposed to HHCs through dermal absorption, inhalation, and dietary intake, the neonates can be exposed as fetuses in utero and via breast milk. Embryos, fetuses, infants, and young children are more sensitive than adults. Clinical exposure of children to chloroform, dichloromethane, ethyl chloride, trichloroethane, and halothane is closely watched.

1842 Ecotoxicology | Halogenated Hydrocarbons Table 9 Toxic effects of some commonly used HHCs in rodents Effect

TCDD

PCB

PBB

Chloronaphthalenes

LD50: mg kg1 Liver Porphyria Necrosis Vit. A deficiency P450 induction Tumors

0.004–0.01

4000–10 000

21 500

0.011–2000

þ þ  þ þ (þ Lung)

þ  þ þ þ

þ   þ þ

þ Atrophy þ



þ

þ

Immune suppression In mice

þ (þ Lung)

Hyperkeratosis In rabbit ear

þ

þ

þ

þ

Embryo toxicity

þ (þ Neonate, postnatals)

þ

þ

Neonates

Data from Kimbrough RD (1981) Chronic toxicity of halogenated biphenyls and related compounds in animals and health effects. In: Khan MAQ and Stanton RH (eds.) Toxicology of Halogenated Hydrocarbons, pp. 23–37. New York: Pergamon.

Table 10 A list of HHCs, which have tested positive for carcinogenicity

HHC

System

Nonmutagenic carcinogenicitya

Chlorobenzilate Chloroform Carbon tetrachloride Dieldrin P, P9-Dichlorodiphenyl dichloroethylene Lindane PCB TCDD Trichloroethylene 1,2-Dichloroethane

Rat liver Rat/mouse liver Rat/mouse Mouse liver Mouse liver

þ þ þ þ þ

Mouse liver Rat/mouse liver Rat liver, lung Mouse liver

þ þ þ þ

1,2-Dibromoethane 1,2-Dibromo-3-chloropropane Hexachloroethane Tetrachloroethylene 1,1,2-Trichloroethane

The effects of halogenated aromatics (PCBs, PCDDs, PCDFs) depend on the type of the compound. They cause acute irritation of eyes, mucus membranes, lungs, and gastrointestinal tract besides affecting nervous systems. These also cause acne (chloracne), liver dysfunction, porphyria, and malignancies (Table 9) and exert developmental effects. Chlorinated toluenes (benzyl and benzal chlorides, benzotrichloride) are group 2A carcinogens. Other HHCs with carcinogenic potential are listed in Table 10. PCDD residues are widely distributed, especially in aquatic environment, fish, and fish-eating birds and mammals. Their residues in human food (Table 11) can have significant chronic effects, especially in the presence of other HHCs. TCDD causes several symptoms of toxicity, such as wasting, fatty liver, lung lesions, hypothyroidism, chloracne, liver cancer (Tables 9 and 10). TCDD-linked

Tumorsb

Kidney, thyroid, liver Liver

Liver Subcutaneous, stomach, blood vessels, mammary gland Subcutaneous, stomach, blood vessels, lung Stomach, mammary gland Liver Liver Liver

cancer has been reported in factory workers in the form of brain cancer and malignant melanomas. PCDF congeners are not as toxic as PCDDs. A list of effects in experimental mammals is summarized in Tables 9 and 10. The daily dietary intake of TCDD in humans (about 118 pg (TEQ) in North America and the Netherlands) is mostly via meats, fish, eggs, milk, and other dairy products (Table 11). There is a federal warning about the consumption of Lake Michigan fish by pregnant women and those expecting pregnancy and of fish in Lake Michigan Basin by children and young adults. The high concentrations of these HHCs in human breast milk have advisories against breast-feeding of infants. In utero exposure to HHC has shown newborn and children and young adults exhibit neurobehavioral deficits, which become more severe with age.

Ecotoxicology | Halogenated Hydrocarbons Table 11 PCDD and PCDF levels in food consumed in USA

Food

Conc. (pg/g fresh wt) Toxic equivalent

Beef Pork Chicken Eggs Dairy products Milk Fish

0.48 0.26 0.19 0.13 0.36 0.07 1.2

The residues of stable/persistent and toxic pesticides used in past are still present in global ecosystems and humans. Their presence in human breast milk has created concerns about effects in neonates leading to neurobehavioral deficits in children and young adults. It will take several decades for their residues to completely disappear. Their residues are still biomagnified in top carnivores. These HHCs are nerve and liver toxins. The LD50 of DDT to mammalian species ranges between 113 and 450 mg/kg body wt. and that of cyclodienes between 40 and 60 mg/kg body wt. Environmental products of cyclodiene insecticides (aldrin, dieldrin, heptachlor, chlordanes), namely their corresponding photoisomers, can become more toxic than the corresponding parent chemical and can be metabolized to even more toxic products. These toxic metabolites result from epoxidation of unsaturated bonds or oxidative dehydrochlorinations. The metabolite of DDT, DDE, is more persistent in environment than DDT and is esterogenic. Methoxychlor, also, has estrogenic effects. DDD, a contaminant in DDT, causes adrenocorticoid atrophy. PCBs have very low water solubility (3–21 mg l1). Individual congeners with chlorine substitution in ortho-position on both rings vary in their persistence, stability, and toxicity. Coplanar PCBs have chlorine in ortho-position on both rings, such as 3,39,4,49tetrachlorobiphenyl. Planars have chlorine substitutions in 2-, 3-, or 4-ortho-positions, which moves rings out of phase because of interactions with adjacent chlorines in different rings. These have globular structures. PCBs are persistent and poorly metabolized in biota and thus are biomagnified in ecosystems harming top carnivores. Their half-life in humans varies from 30 days to 10 years. PCBs are transferred to offspring through the placenta and via milk. They cause neurobehavioral deficits in neonates due to their exposure in utero as fetuses. Birth defects and lowering of male sex hormones (testicular atrophy) are reported in several bird and mammalian species. PBBs are used as fire retardants (Fire master) and resemble PCBs in their effects. TCAB and TCAOBs are immunosuppressive agents and may even affect anterior pituitary secretion of ACTH.

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See also: Reproductive Toxicity.

Further Reading Adams WJ, Chapman GA, and Landis WG (eds.) (1988) Aquatic Toxicology and Hazard Assessment, vol. 10, 579pp. Philadelphia: ASTM. Anonymous (1979) Environmental Quality. The Annual Report of Council on Environmental Quality, 816pp. Washington, DC: US Government Printing Office. Anonymous (1985) The Effects of Great Lakes Contaminanats on Human Health. Report to Congress. USEPA 905-R-95-107, Sep. 1985. Chicago: Great Lakes National Program Office. Anonymous (1988) The Great Lakes Clean-up effort. Chemical and Engineering News Frb 2: 22–27. Avono S, Tanabe S, Fujise Y, Kato H, and Tatsukawa R (1998) Persistent organochlorines in mink whale (Balaenoptera acutorostrata) and their prey species from the Antarctic and the north Pacific. Environmental Pollution 98: 81–89. Brown AWA (1982) Ecology of Pesticides, 340pp. New York: Plenum. Brooks GT (1974) Chlorinated Hydrocarbons. Columbus: CRC Press. Carey T, Cook P, Giesy J, et al. (1998) Ecotoxicological Risk Assessment of the Chlorinated Organic Chemicals, 375pp. Pensacola, FL: SETAC Press. Colborn T, Dumanoski D, and Myers JP (1995) Our Stolen Future. New York: Dutton Press. Court GS, Davis LS, Focardi S, et al. (1997) Chlorinated hydrocarbons in the tissues of south polar skuas (Catharacta macocormicki) and Adelie penguins (Pygoscelis adeliea) from Ross Sea, Antarctica. Environmental Pollution 97: 295–301. Evenenset A, Christensen GN, and Kallenborn R (2005) Selected chlorbornanes, polychlorinated naphthalenes, and brominated flame retardants in Bjornoya (Bear Island) freshwater biota. Environmental Pollution 136: 419–430. Hansen LG (1994) Halogenated aromatic hydrocarbons. In: Cockerham LG and Shane BS (eds.) Basic Environmental Toxicology, pp. 199–230. Ann Arbor, MI: CRC Press. Home AS and Ho IK (1994) Toxicity of solvents. In: Cockerham LG and Shane BS (eds.) Basic Environmental Toxicology, pp. 157–184. Ann Arbor, MI: CRC Press. Hutzinger O, Frei RW, Merian E, and Pocchiari F (1982) Chlorinated Dioxins and Related Compounds, 558pp. New York: Pergamon. Khan MAQ (1976) Pesticides in Environment, 320pp. New York: Plenum. Khan MAQ (1990) Biochemical effects of pesticides on mammals. In: Haug G and Hoffman H (eds.) Chemistry of Plant Protection, vol. 6, pp. 109–172. Berlin: Springer. Khan MAQ and Stanton RH (1981) Toxicology of Halogenated Hydrocarbons. New York: Pergamon. Kimbrough RD (1981) Chronic toxicity of halogenated biphenyls and related compounds in animals and health effects. In: Khan MAQ and Stanton RH (eds.) Toxicology of Halogenated Hydrocarbons, pp. 23–37. New York: Pergamon. McEwen FL and Stephenson GR (1979) The Use and Significance of Pesticides in the Environment, 538pp. New York: Wiley Interscience. Snyder R and Andrews LS (1995) Toxic effects of solvents and vapors. In: Klaassen CD (ed.) Toxicology – The Basic Science of Poisons, 5th edn., pp. 737–772. New York: McGraw. Sun YV, Boverhof DR, Bourgon LD, Fielden MR, and Zacherowski TR (2004) Comparative analysis of dioxin response elements in human, mouse, and rat genomic sequence. Nucleic Acid Research 32: 4512–4522. USEPA (1994) Health Assessment Document for 2,3,7,8Tetrachlorodibenzo-p-dioxin (TCDD) and related compounds. Review draft. Vol. II, August 1994. Walker CH, Hopkin SP, Silby RM, and Peakall DB (2006) Principles of Ecotoxicology, 3rd edn. New York: Taylor and Francis. Weisburger HE (1981) Halogenated substances in environmental and industrial materials. In: Khan MAQ and Stanton RH (eds.) Toxicology of Halogenated Hydrocarbons, pp. 3–24. New York: McGraw.