Childhood Cancer: Solvents: Benzene and TCE

A variety of solvents, including benzene, carbon tetrachloride, methylene chloride, styrene, toluene, trichloroethylene (TCE), tetrachloroethylene (PCE), and xylene, have been linked to various types of cancer (Clapp et al. 2005). Occupational exposures to benzene, carbon tetrachloride, and TCE have been linked with an increased risk of cancer (Glass et al. 2003; Wilcosky et al. 1984; Scott and Chiu 2006). Of these chemicals, the strongest causal association between exposure and cancer development is for benzene, where relatively low levels of exposure have been linked to cancer (Smith et al. 2007; Mehlman 2006). A strong associated has also been established between parental occupational exposure to these solvents and an increased risk of childhood leukemia in their children. Limited data also exists that suggests a link between paternal exposure to solvents such as well paints and/or inks and an increased risk for central nervous system (CNS) or brain cancer among their children (Feychtinget al. 2001; Colt and Blair, 1995).

Direct exposure to organic solvents such as benzene, TCE, PCE, and styrene during childhood has also been associated with an increased risk for the development of cancer, specifically Non-Hodgkin’s Lymphoma (NHL). Numerous case-control studies have associated increased prevalence of NHL among children who live near railways, oil refineries, and petrochemical plants with an increased exposure to solvents, primarily benzene (Clapp et al. 2005; Fagliano et al. 2003). Furthermore, case control studies have demonstrated increased risks of NHL among children whose fathers had occupational exposures to solvents, indicating that germline cell (in this case, sperm) DNA mutations from solvent exposure may have the potential to cause cancer in one’s offspring (Clapp et al. 2005).

For childhood cancers, the solvents benzene and trichloroethylene are of particular concern, due to the increased risk of carcinogenesis they pose, their prevalence in industry, and their ability to persist in the environment (IARC 1987, IARC 1995, ATSDR 2003). The International Agency for Research on Cancer (IARC) has classified benzene as a Group 1 carcinogen (known human carcinogen) and TCE is classified as a Group 2A carcinogen (probable human carcinogen); the EPA has also classified benzene as a known human carcinogen (EPA 2008a) and acknowledges the evidence of TCE as a potential human carcinogen, although it has made no formal carcinogen classification of the latter (IARC 1995, EPA 2008b).

This section provides background information on the presence and potential health effects of these solvents and reviews existing Michigan policies related to regulating these solvents. Best policy practices from other states are highlighted and recommendations are provided to further protect Michigan’s children from exposure to these solvents.

Background Information

Sources and Routes of Exposure

Solvents are a class of liquid organic chemicals that are generally used to dissolve or dilute materials that are otherwise insoluble in water. There are many different types of solvents, but most solvents are derived from petroleum. Solvents are widely used in industry and in households in paints, varnishes, lacquers, inks, aerosols, dyes, adhesives, fuels, and fuel additives (Bruckner, Warren 2001). Although most daily human exposure to solvents involves exposure to a complex mixture of chemicals, this section will focus on only two of the many common solvents for which we have the strongest data on possible links to cancer in childhood: benzene and 1,1,2-trichloroethylene (TCE).

Benzene

Benzene, an aromatic hydrocarbon, was historically used as a general purpose solvent, but it is currently used primarily in the production of plastics, resins, and some synthetic and nylon fibers (Bruckner, Warren 2001; Clapp et al. 2005). Benzene is also used in the production of some types of rubbers, lubricants, dyes, detergents, drugs and pesticides (Clapp et al. 2005).

Benzene is found in crude oil and can be released during incomplete combustion of fossil fuels (Belsonet al. 2007; Clapp et al. 2005). In addition, benzene is added to gasoline to reduce knocking, and accounts for roughly 1-2% by volume of gasoline (Bruckner, Warren 2001). These sources (gasoline vapor and transportation exhaust) account for a large proportion of the benzene component of outdoor air contamination, and the majority of benzene exposure among nonsmokers (Bruckner and Warren 2001; EPA 2007; Wallace 1996). Benzene is found in cigarette smoke, and environmental tobacco smoke is a major source of indoor benzene exposure in places where indoor smoking occurs (Wallace 1996). Benzene is also added to some paints and hobby glues, which can also serve as important points of exposure. (Belson et al. 2007).

Like most solvents, the primary exposure route for benzene is via inhalation of contaminated air or vapors. Other possible exposure routes include dermal absorption after direct contact with substances containing benzene or ingestion of drinking water contaminated with benzene (Bruckner and Warren 2001).

Acute effects of high levels of benzene exposure, either through inhalation or consumption, can include dizziness, drowsiness, increased heart rate, confusion, headaches, and unconsciousness; rapid exposure to very high levels of benzene can result in death (Agency for Toxic Substances and Disease Registry, 2011; EPA 2000). Benzene has a well-documented association with cancer, and is classified as a Group A human carcinogen by the EPA (EPA 2000). Non-cancer chronic health effects of benzene exposure, which will not be discussed further in this section, may include blood disorders, impaired fertility in women, and low birth weight (EPA 2000). Leaking underground storage tanks (USTs) may be a potential source.

Relatively few epidemiologic studies concerning the association between leaking underground storage tanks and cancer have been conducted. Notably, researchers found an increased risk of leukemia in the affected area of a gasoline spill from a UST in Pennsylvania. This association suggests a possible association between long-term exposures to benzene in gasoline vapors from UST spills and the development of leukemia (Talbott et al. 2011).

Follow this link for a map of leaking underground storage tanks in Michigan: (http://circleofblue.org/LUST.html).

TCE

TCE (1,1,2-trichloroethylene) is a halogenated hydrocarbon, and is widely used as a metal degreasing solvent (Bruckner and Warren 2001). TCE is also used in the U.S. in adhesive solvents, in paints and varnishes, in printing inks, and as a paint stripper. Vapor from degreasing operations is responsible for the bulk of atmospheric TCE emissions in the U.S. (Wu and Schaum 2000; Clapp et al. 2005). TCE can also be released into the air from hazardous waste incinerators, and into the water from leaching landfills or industrial discharges (Wu and Schaum 2000). Therefore, children may be exposed to TCE via inhalation of vapors or contaminated air, ingestion of contaminated drinking water, or via direct dermal contact with TCE or contaminated water. Because TCE readily volatizes from water, significant exposure may also occur via inhalation during showering or bathing when drinking water is contaminated (Wu and Schaum 2000).

Childhood Exposure to Benzene and TCE

Childhood Exposure in the US

A study by the Environmental Working Group (EWG) collected data from 39,751 public water suppliers in 42 states from 1998-2003. The study found that benzene was reported as present in the drinking water from 31,920 of those plants – plants that provide drinking water for over 1.7 million people in the U.S. Benzene levels were above EPA limits for drinking water [5 ppb (parts per billion)] for nearly 500,000 of those people. These higher ratings were found in 116 communities spread over 26 states (EWG 2005).

The EWG study found that 31,909 public water suppliers reported TCE in their final product, accounting for the drinking water of nearly 1.3 million people. Levels were above EPA limits (5 ppb) for more than 13,000 people (EWG 2005). While the number of highly contaminated areas is fewer than for benzene, TCE contamination is widespread.

Another study found that TCE is the most commonly reported organic contaminant in drinking water, and persons consuming drinking water originating from private wells may be at higher risk for exposure to TCE, particularly if the well is in the vicinity of a landfill or contaminated waste site. This study also found that between 9% and 34% of Another study found that TCE is the most commonly reported organic contaminant in drinking water, and persons consuming drinking water originating from private wells may be at higher risk for exposure to TCE, particularly if the well is in the vicinity of a landfill or contaminated waste site. This study also found that between 9% and 34% of public drinking water supply systems are thought to have some TCE contamination, and average daily intake of TCE via water in the general population is estimated to be between 2 and 20 micrograms (µg) per day. The authors of this study also estimated that the general population is exposed to roughly 18 µg TCE per day simply by breathing the air (Wu and Schaum 2000).

Childhood Exposure in Michigan

In 2007, 356,291 pounds of benzene were released into the air in Michigan from industrial facilities required to report releases through the EPA’s Toxic Release Inventory (TRI) program. Just over 1,305 pounds of benzene were disposed of at off-site facilities, while 2,653 pounds were disposed of at publicly-owned sites and 111,081 pounds were disposed of at off-site treatment facilities (MDEQ 2007).

In 2009, 79,586 pounds of benzene were released into the air in Michigan from industrial facilities required to report releases through the EPA’s Toxic Release Inventory (TRI) program. The majority of these releases were in Alpena, River Rouge, Ecorse, and Detroit. Of the 40 Superfund sites throughout Michigan there are currently 40 which are reported to contain benzene (EPA 2011).

TCE is present at 19 of Michigan’s 434 Superfund sites, and in 2009, approximately 41,827 pounds of TCE were released into the air from facilities required to report releases through TRI, with the majority of releases occurring in Howell, Monroe, Boyne City, and Adrian (EPA 2011; RTKnet 2011).

An Environmental Working Group analysis showed that 112,000 people from 12 Michigan communities drank tap water containing trichloroethylene between 1998 and 2003. In one of these communities, Gaines Township, 1,227 people were exposed at levels exceeding the EPA’s enforceable limit for trichloroethylene in drinking water of 5 ppb (EWG 2005).

Figure 1shows Michigan locations where any of a group of 21 Volatile Organic Compounds, including benzene and trichloroethylene, has been found in drinking water. Figure 2 shows Michigan Superfund sites containing TCE or benzene, as of 2008; at this time 12 sites contained TCE and 32 sites contained benzene (EPA 2011).

Figure 1.County Volatile Organic Compound Maps for Michigan.Source: MDEQ (1983-2002). Water Quality Maps for Michigan by County. Accessed September 8, 2009 at: http://www.deq.state.mi.us/documebnts/deq-wd-gws-ciu-voc.htm.

Figure 2. Location of Superfund sites within Michigan containing benzene (orange), TCE (yellow), or both TCE and benzene (red) as of 2008 (EPA 2011)

Solvents and Cancer

Exposure to solvents during childhood and prenatally—and even parental exposure to solvents prior to conception—has been hypothesized as a risk factor for development of cancer during childhood or later in life. This section will briefly discuss the evidence surrounding benzene and TCE exposure and cancer development. However, it is important to note that exposure to solvents often occurs in mixtures, and therefore solvent-specific conclusions regarding cancer risk become difficult to make with certainty (Wartenberget al. 2000). Nonetheless, such exposure misclassifications are likely to reduce the appearance of correlations between certain chemicals and cancer (Wartenberg et al. 2000), which suggests there could be more substance to the positive associations discussed below.

Benzene

Benzene is a known carcinogen, and is classified by the EPA and IARC as such (EPA 2007, IARC 1987). Benzene has frequently been associated with leukemia, particularly acute myeloid leukemia (AML), in occupational studies of adults (Belson et al. 2007; Smith et al. 2011) and it has been shown to damage DNA in animal studies (EPA 2007).Because benzene is detectable in significant concentrations in ambient air in the U.S. (EPA 2007), assessment of exposure and health effects in the general population is difficult; however, Smith et al. (2011) estimate that as much as 5% of all leukemia cases in the United States are caused by benzene exposure, with the most likely estimate to be 1% (the causes of 82% of leukemia cases remain unknown). As there were an estimated 43,050 new leukemia cases in 2010(American Cancer Society, 2010), that would mean a likely 430 and up to 2,150 cases of leukemia are attributable to benzene exposure annually.

While benzene exposure has primarily been linked to AML in adults thus far, there are indications that it may cause acute lymphoblastic leukemia (ALL) and AML in children as well. For example, proximity to gas stations and road traffic has been associated with childhood leukemia in epidemiologic studies (Belson et al. 2007; Brosselin et al. 2009). Although some studies evaluating risk of childhood cancer from benzene exposure have presented conflicting results (EPA 2007), there are mechanistic explanations which back up the epidemiological evidence for a causal association between childhood leukemia and benzene exposure (Smith 2010). More research is needed to fully assess if a causal association exists benzene exposure and childhood leukemia.

Studies of neonatal blood samples have suggested that DNA mutations which lead to the development of childhood leukemia tend to be present in utero in children that develop childhood leukemia (Smith 2010, Wiemels et al. 1999). Smith (2010) asserts that this may be an indication that a mother’s exposure to benzene or other carcinogens during pregnancy, or even the pre-conception exposure prior to conception in either parent may lead to mutations which can cause the development of childhood leukemia. Furthermore, a variety of studies have found associations with parental exposures to a variety of solvents, some which contain benzene, and the development of childhood cancer (Buka et al. 2007). More research is still needed before a definitive link between parental exposures to benzene and childhood leukemia development can be determined, as well as the mechanism for leukemia development (Anderson et al. 2006).

Many factors could increase childhood exposure and susceptibility to benzene exposure including: activity patterns, breathing and metabolic rates, or biochemical processes that increase sensitivity to benzene (EPA 2007). These factors, coupled with the above data on the known carcinogenicity of benzene in humans and animals, suggest that it is critical to minimize childhood exposure to benzene.

TCE

TCE has been the subject of regulatory, scientific, and political attention for years. The IARC classifies TCE as a probable human carcinogen, and the EPA acknowledges the epidemiologic evidence suggesting links between TCE and cancer, and acknowledges that it is a likely human carcinogen, but has yet to come to a full consensus on whether to officially classify it as such (IARC 2007, EPA 2011). Elevated incidence of many different types of cancers with TCE exposure has been well documented in occupational settings, but there is a possibility that this association between exposure to TCE and cancer development in such settings may be confounded by exposure to other carcinogenic substances (Wartenberg et al. 2000, Bruckner and Warren 2001). In adults, TCE is most strongly associated with increased risk of kidney cancer, liver cancer, and non-Hodgkins lymphoma, and more weakly associated with excess incidence of multiple myeloma, Hodgkin’s lymphoma, and prostate, skin, and cervical cancers (Bruckner and Warren 2001; Wartenberg et al. 2000; Scott and Chiu, 2006). However, these studies have been primarily conducted in populations with elevated exposure (such as in occupational settings) (Bruckner and Warren 2001), and many uncertainties regarding TCE’s toxicology and mechanisms of action remain (Bruckner and Warren 2001). While some research has been done to elucidate the mechanism of TCE-induced kidney and liver cancer development, the numerous uncertainties in our understanding of these mechanisms make it is highly difficulty to determine safe exposure levels (Bruckner and Warren 2001; Scott and Chiu, 2006).

Policy Summary and Analysis

Evidence of the carcinogenicity of benzene and trichloroethylene and of children’s potential exposures to these chemicals supports the need to protect children from these chemicals.

Benzene

1. Michigan Policy Highlights
   1. In Michigan, hazardous materials, including benzene, are to be kept, transported, handled, and disposed of in a manner that shall not risk a fire hazard or menace to public peace, health, or safety, or cause risk of loss or damage to persons or property (MCL § 29.5).
   2. Suspected or confirmed leakages of underground storage tanks containing fuel must be reported to the state within 24 hours. It is the owner’s responsibility to identify and mitigate any hazards
2. Analysis and Policy Highlights of Other States
   1. The California legislature considers benzene a toxic air contaminant released by cars and trucks. As such, all schools must be at least 500 feet from freeways and very busy roadways, as concentrations of benzene from fuel exhaust were found to be highest within 500 feet of roads (Cal Ed Code 17213; Cal Pub Resources Code 21151.8).
   2. In California, gasoline and diesel pumps are required to have hold-open latches in order to reduce the risk of consumers coming in contact with benzene in fuel. The implementation cost of this statute at a typical gas station was estimated to be only $55 (Cal Health &Saf Code 41960.6).
   3. In Vermont, all underground storage tanks holding fuel, oil, or non-petroleum hazardous chemicals must be registered with the Vermont Department of Environmental Conservation (Vermont Department of Environmental Conservation, 2009).
3. Evaluations and Recommendations
   1. Michigan should enact more stringent practices to reduce exposure to benzene in fuel exhaust. These should include changes made to fueling station systems in the state and building codes placing greater distances between busy roadways and certain types of buildings, including schools.
   2. Require fueling stations to have “hold-open” latches at fuel pumps, allowing consumers to avoid inhalation of fuel fumes and the benzene contained in the fuel, as California has done.

1,1,2-Trichloroethylene

1. Michigan Policy Highlights
   1. There was no Michigan legislation that met the criteria for our search.

1. Analysis and Policy Highlights from Other States
   1. In Montana, it is unlawful for any person to distribute, sell, or offer for sale within the state quantities of 20 gallons or more of any halogenated solvent annually—including TCE—to any single purchaser for commercial or government use unless the purchaser possesses proof of registration with the state government (Mont. Code Anno. § 75-10-451).
   2. In Pennsylvania, it is unlawful for any person or municipality to put, place, discharge, or allow the discharge of TCE into the waters of the Commonwealth, or to perform actions discharging TCE from property owned by the person or municipality that would result in TCE being discharged into the waters of the Commonwealth (35 P.S. § 691.401).
   3. In Virginia, it is unlawful for any person to knowingly sell or distribute for retail sale in the Commonwealth any product used in or as adhesives for hardwood floors if they contain TCE. It is also unlawful to sell or distribute for retail sale in the Commonwealth any product for household or residential use that contains TCE manufactured on or after January 1, 2004 (Va. Code Anno. § 10.1-1424.2).
2. Evaluations and Recommendations
   1. Michigan should prohibit the discharge of TCE and mixtures containing TCE into any water source within the state’s borders.
   2. Michigan should ban household products containing TCE.
   3. Michigan should limit the amount of TCE purchased per customer.

Summary of Recommendations for Solvent Policy in Michigan

Michigan currently has very limited legislation regarding public health and solvents. In order to strengthen policy and protect the health of Michigan residents, the state should:

• Enact legislation requiring that newly constructed schools and daycare centers be built away from busy roadways where exposure to benzene in fuel exhaust is heightened, similar to what has been done in California.
• Require fueling stations to have “hold-open” latches at fuel pumps, allowing consumers to avoid inhalation of fuel fumes and the benzene contained in the fuel, as California has done.
• Ban household products containing 1,1,2-trichloroethylene, as has been done in Virginia.
• Ban the discharge of TCE or any compounds or mixtures containing TCE into bodies of water within the state or under the jurisdiction of the state, similar to what has been done in Pennsylvania.
• Limit the amount of TCE that may be purchased by any single person or entity for a given time period, like what has been done in Montana.

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