Air Quality and Health and Welfare
2.7 Toxic Materials
2.7.5 Gaseous Air Toxics
2.7.5.1 Benzene
Benzene is an aromatic hydrocarbon which is present as a gas in both exhaust and evaporative emissions from motor vehicles. Benzene in the exhaust, expressed as a percentage of total organic gases (TOG), varies depending on control technology (e.g., type of catalyst) and the levels of benzene and other aromatics in the fuel, but is generally about three to five percent. The benzene fraction of evaporative emissions depends on control technology and fuel composition and characteristics (e.g., benzene level and the evaporation rate) and is generally about one percent (“Analysis of the Impacts of Control Programs on Motor Vehicle Toxics Emissions,” 1999).
The EPA has recently reconfirmed that benzene is a known human carcinogen by all routes of exposure (“Carcinogenic Effects of Benzene: An Update,” 1998). Respiration is the major source of human exposure. Long-term respiratory exposure to high levels of ambient benzene concentrations has been shown to cause cancer of the tissues that form white blood cells. Among these are acute nonlymphocytic leukemia, chronic lymphocytic leukemia and possibly multiple myeloma (primary malignant tumors in the bone marrow), although the evidence for the latter has decreased with more recent studies (“Interim Quantitative Cancer Unit Risk Estimates Due to Inhalation of Benzene,” (1985) and “Motor Vehicle Air Toxics Health Information,” 1991). Leukemia is a blood disease in which the white blood cells are abnormal in type or number. Leukemia may be divided into nonlymphocytic (granulocytic) leukemias and lymphocytic leukemias. Nonlymphocytic leukemia generally involves the types of white blood cells (leukocytes) that are involved in engulfing, killing, and digesting bacteria and other parasites (phagocytosis) as well as releasing chemicals involved in allergic and immune responses. This type of leukemia may also involve erythroblastic cell types (immature red blood cells). Lymphocytic leukemia involves the lymphocyte type of white bloods cell that are responsible for the immune responses. Both nonlymphocytic and lymphocytic leukemia may, in turn, be separated into acute (rapid and fatal) and chronic (lingering, lasting) forms. For example; in acute myeloid leukemia (AML) there is diminished production of normal red blood cells (erythrocytes), granulocytes, and platelets (control clotting) which leads to death by anemia, infection, or hemorrhage. These events can be rapid. In chronic myeloid leukemia (CML) the leukemic cells retain the ability to differentiate (i.e., be responsive to stimulatory factors) and perform function; later there is a loss of the ability to respond. Leukemias, lymphomas, and other tumor types have been observed in experimental animals exposed to benzene by inhalation or oral administration. Exposure to benzene and/or its metabolites has also been linked with genetic changes in humans and animals (“IARC Monographs on the Evaluation of Cacinogenic Risk of Chemicals to Humans,” 1982, p. 345-389) and increased proliferation of mouse bone marrow cells (Irons, Stillman, Colagiovanni, & Henry, 1992). The occurrence of certain chromosomal changes in individuals with known exposure to benzene may serve as a marker for those at risk for contracting leukemia (Lumley, Barker, Murray, 1990).
The latest assessment by EPA places the excess risk of developing acute nonlymphocytic leukemia at 2.2 H 10-6 to 7.7 H 10-6/:g/m3. There is a risk of about two to eight excess acute nonlymphocytic leukemia cases in one million people exposed to 1:g/m3 over a lifetime (70 years) (“Carcinogenic Effects of Benzene: An Update,” 1998). This range of unit risk represents the maximum likelihood (MLE) estimate of risk, not an upper confidence limit (UCL).
A number of adverse noncancer health effects, blood disorders such as preleukemia and aplastic anemia, have also been associated with low-dose, long-term exposure to benzene (“Motor Vehicle-Related Air Toxics Study,” 1993). People with long-term exposure to benzene may experience harmful effects on the blood-forming tissues, especially the bone marrow. These effects can disrupt normal blood production and cause a decrease in important blood components, such as red blood cells and blood platelets, leading to anemia (a reduction in the number of red blood cells), leukopenia (a reduction in the number of white blood cells), or thrombocytopenia (a reduction in the number of blood platelets, thus reducing the ability for blood to clot). Chronic inhalation exposure to benzene in humans and animals results in pancytopenia. Pancytopenia is the reduction in the number of all three major types of blood cells (erythrocytes, or red blood cells, thrombocytes, or platelets, and leukocytes, or white blood cells). In adults, all three major types of blood cells are produced in the bone marrow of the vertebra, sternum, ribs, and pelvis. The bone marrow contains immature cells, known as multipotent myeloid stem cells, that later differentiate into the various mature blood cells. Pancytopenia results from a reduction in the ability of the red bone marrow to produce adequate numbers of these mature blood cells.a condition characterized by decreased numbers of circulating erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (blood platelets) (Aksoy, 1991 and Goldstein, 1988). Individuals that develop pancytopenia and have continued exposure to benzene may develop aplastic anemia. Aplastic anemia is a more severe blood disease and occurs when the bone marrow ceases to function, i.e.,these stem cells never reach maturity. The depression in bone marrow function occurs in two stages - hyperplasia, or increased synthesis of blood cell elements, followed by hypoplasia, or decreased synthesis. As the disease progresses, the bone marrow decreases functioning. This myeloplastic dysplasia (formation of abnormal tissue) without acute leukemiais known as preleukemia. The aplastic anemia can progress to AML (acute mylogenous leukemia). Others may exhibit both pancytopenia and bone marrow hyperplasia (excessive cell formation), a condition that may indicate a preleukemic state (Aksoy, Erdem, & DinCol, 1974 and Aksoy & Erdem, 1978). The most sensitive noncancer effect observed in humans is the depression of absolute lymphocyte counts in the circulating blood (Rothman, Li, Dosemeci, Bechtold, Marti, Wang, Linet, Xi, Lu, Smith, Titenko-Holland, Zhang, Blot, Yin, & Hayes, 1996).
2.7.5.2 Formaldehyde
Formaldehyde is the most prevalent aldehyde in vehicle exhaust. It is formed for incomplete combustion of both gasoline and diesel fuel and accounts for one to four percent of total exhaust TOG emissions, depending on control technology and fuel composition. It is not found in evaporative emissions.
Formaldehyde exhibits extremely complex atmospheric behavior (Ligocki, Whitten, Schulhof, Causley, & Smylie, 1991)It is formed by the atmospheric oxidation of virtually all organic species, including biogenic (produced by a living organism) hydrocarbons. Mobile sources contribute both primary formaldehyde (emitted directly from motor vehicles) and secondary formaldehyde (formed from photooxidation of other VOCs emitted from vehicles).
EPA has classified formaldehyde as a probable human carcinogen based on limited evidence for carcinogenicity in humans and sufficient evidence of carcinogenicity in animal studies, rats, mice, hamsters, and monkeys (“Assessment of health risks to garment workers,” 1987). Epidemiological studies in occupationally exposed workers suggest that long-term inhalation of formaldehyde may be associated with tumors of the nasopharyngeal cavity (generally the area at the back of the mouth near the nose), nasal cavity, and sinus. Studies in experimental animals provide sufficient evidence that long-term inhalation exposure to formaldehyde causes an increase in the incidence of squamous (epithelial) cell carcinomas (tumors) of the nasal cavity. The distribution of nasal tumors in rats suggests that not only regional exposure but also local tissue susceptibility may be important for the distribution of formaldehyde-induced tumors (“Motor Vehicle Air Toxics Health Information,” 1991). Research has demonstrated that formaldehyde produces mutagenic activity in cell cultures (“Motor Vehicle-Related Air Toxics Study,” 1993).
The MLE estimate of a lifetime extra cancer risk from continuous formaldehyde exposure is about 1.3 H 10-6/:g/m3. In other words, it is estimated that approximately 1 person in one million exposed to 1 :g/m3 formaldehyde continuously for their lifetime (70 years) would develop cancer as a result of this exposure.
Formaldehyde exposure also causes a range of noncancer health effects. At low concentrations (0.05-2.0 ppm), irritation of the eyes (tearing of the eyes and increased blinking) and mucous membranes is the principal effect observed in humans. At exposure to 1-11 ppm, other human upper respiratory effects associated with acute formaldehyde exposure include a dry or sore throat, and a tingling sensation of the nose. Sensitive individuals may experience these effects at lower concentrations. Forty percent of formaldehyde-producing factory workers reported nasal symptoms such as rhinitis (inflammation of the nasal membrane), nasal obstruction, and nasal discharge following chronic exposure (Wilhelmsson & Holmström, 1987). In persons with bronchial asthma, the upper respiratory irritation caused by formaldehyde can precipitate an acute asthmatic attack, sometimes at concentrations below 5 ppm (Burge, Harries, Lam, O’Brien, Patchett, 1985). Formaldehyde exposure may also cause bronchial asthma-like symptoms in nonasthmatics (Hendrick, Rando, Lane, & Morris, 1982 and Nordman, Keskinen, & Tuppurainen, 1985).
Immune stimulation may occur following formaldehyde exposure, although conclusive evidence is not available. Also, little is known about formaldehyde's effect on the central nervous system. Several animal inhalation studies have been conducted to assess the developmental toxicity of formaldehyde: The only exposure-related effect noted in these studies was decreased maternal body weight gain at the high-exposure level. No adverse effects on reproductive outcome of the fetuses that could be attributed to treatment were noted. An inhalation reference concentration (RfC), below which long-term exposures would not pose appreciable non-cancer health risks, is not available for formaldehyde at this time.
2.7.5.3 Acetaldehyde
Acetaldehyde is a saturated aldehyde that is found in vehicle exhaust and is formed as a result of incomplete combustion of both gasoline and diesel fuel. It is not a component of evaporative emissions. Acetaldehyde comprises 0.4 to 1.0 percent of exhaust TOG, depending on control technology and fuel composition (“Analysis of the Impacts of Control Programs on Motor Vehicle Toxics Emissions,” 1999).
The atmospheric chemistry of acetaldehyde is similar in many respects to that of formaldehyde (Ligocki et al., 1991). Like formaldehyde, it is produced and destroyed by atmospheric chemical transformation. Mobile sources contribute to ambient acetaldehyde levels both by their primary emissions and by secondary formation resulting from their VOC emissions. Acetaldehyde emissions are classified as a probable human carcinogen. The MLE estimate of a lifetime extra cancer risk from continuous acetaldehyde exposure is about 0.78 ? 10-6 /?g/m3. In other words, it is estimated that less than 1 person in one million exposed to 1 ?g/m3 acetaldehyde continuously for their lifetime (70 years) would develop cancer as a result of their exposure.
Non-cancer effects in studies with rats and mice showed acetaldehyde to be moderately toxic by the inhalation, oral, and intravenous routes (“Health Assessment Document for Acetaldehyde,” 1987 and “Preliminary Draft: Proposed identification of acetaldehyde as toxic air contaminant,” 1992 and “Acetaldehyde,” 1997). The primary acute effect of exposure to acetaldehyde vapors is irritation of the eyes, skin, and respiratory tract. At high concentrations, irritation and pulmonary effects can occur, which could facilitate the uptake of other contaminants. Little research exists that addresses the effects of inhalation of acetaldehyde on reproductive and developmental effects. The in vitro and in vivo studies provide evidence to suggest that acetaldehyde may be the causative factor in birth defects observed in fetal alcohol syndrome, though evidence is very limited linking these effects to inhalation exposure. Long-term exposures should be kept below the reference concentration of 9 ?g/m3 to avoid appreciable risk of these non-cancer health effects (“2,4-Dinitrophenol,” 1999).
2.7.5.4 1,3-Butadiene
1,3-Butadiene is formed in vehicle exhaust by the incomplete combustion of fuel. It is not present in vehicle evaporative emissions, because it is not present in any appreciable amount in fuel. 1,3-Butadiene accounts for 0.4 to 1.0 percent of total exhaust TOG, depending on control technology and fuel composition (“Analysis of the Impacts of Control Programs on Motor Vehicle Toxics Emissions,” 1999).
1,3-Butadiene was classified by EPA as a Group B2 (probable human) carcinogen in 1985 (“Mutagenicity and Carcingenicity Assessment of 1,3-Butadine,” 1985). This classification was based on evidence from two species of rodents and epidemiologic data. EPA recently prepared a draft assessment to determine if sufficient evidence exists to propose that 1,3-butadiene be classified as a known human carcinogen (“Health Assessment of 1,3-Butadiene,” 1998). However, the Environmental Health Committee of EPA’s Scientific Advisory Board (SAB), in reviewing the draft document, issued a majority opinion that 1,3-butadiene should instead be classified as a probable human carcinogen (“An SAB Report: Review of the Health Risk of 1,3 Butadiene,” 1998). The SAB panel recommended that EPA calculate the lifetime cancer risk estimates based on the human data from Delzell et al. (1995) and account for the highest exposure of “360 ppm-year” for 70 years. Based on this calculation (Koppikar, 1999) the maximum likelihood estimate of lifetime cancer risk from continuous 1,3-butadiene exposure is 2.21 ? 10-6/microgram/m3. This estimate implies that approximately 2 people in one million exposed to 1 microgram/m3 1,3-butadiene continuously for their lifetime (70 years) would develop cancer as a result of their exposure.
An adjustment factor of 3 can be applied to this potency estimate to reflect evidence from rodent studies suggesting that extrapolating the excess risk of leukemia in a male-only occupational cohort may underestimate the total cancer risk from 1,3-butadiene exposure in the general population (Koppikar, 2000). First, studies in both rats and mice indicate that 1,3-butadiene is a multi-site carcinogen. It is possible that humans exposed to 1,3-butadiene may also be at risk of cancers other than leukemia and that the epidemiologic study had insufficient power to detect excess cancer risks for other tissues or sites in the body. Second, both the rat and mouse studies suggest that females are more sensitive to 1,3-butadiene-induced carcinogenicity than males, and the female mammary gland was the only 1,3-butadiene-related tumor site common to both species. Use of a 3-fold adjustment to the potency estimate of 2.21 ? 10-6/microgram/m3 derived from the occupational epidemiologic study yields a upper bound cancer potency estimate of 1.4 ? 10-5/microgram/m3, which roughly corresponds to a combination of the human leukemia and mouse mammary gland tumor risk estimates, at least partially addressing the concerns that the leukemia risk estimated from the occupational data may underestimate total cancer risk to the general population, in particular females.
2.7.5.5 Acrolein
Acrolein is extremely toxic to humans from the inhalation route of exposure, with acute exposure resulting in upper respiratory tract irritation and congestion. The US EPA developed a reference concentration for inhalation (RfC) of acrolein of 0.02 micrograms/m3 1993. Although no information is available on its carcinogenic effects in humans, based on laboratory animal data, EPA considers acrolein a possible human carcinogen (“Acrolein,” 1993).
Benzene is an aromatic hydrocarbon which is present as a gas in both exhaust and evaporative emissions from motor vehicles. Benzene in the exhaust, expressed as a percentage of total organic gases (TOG), varies depending on control technology (e.g., type of catalyst) and the levels of benzene and other aromatics in the fuel, but is generally about three to five percent. The benzene fraction of evaporative emissions depends on control technology and fuel composition and characteristics (e.g., benzene level and the evaporation rate) and is generally about one percent (“Analysis of the Impacts of Control Programs on Motor Vehicle Toxics Emissions,” 1999).
The EPA has recently reconfirmed that benzene is a known human carcinogen by all routes of exposure (“Carcinogenic Effects of Benzene: An Update,” 1998). Respiration is the major source of human exposure. Long-term respiratory exposure to high levels of ambient benzene concentrations has been shown to cause cancer of the tissues that form white blood cells. Among these are acute nonlymphocytic leukemia, chronic lymphocytic leukemia and possibly multiple myeloma (primary malignant tumors in the bone marrow), although the evidence for the latter has decreased with more recent studies (“Interim Quantitative Cancer Unit Risk Estimates Due to Inhalation of Benzene,” (1985) and “Motor Vehicle Air Toxics Health Information,” 1991). Leukemia is a blood disease in which the white blood cells are abnormal in type or number. Leukemia may be divided into nonlymphocytic (granulocytic) leukemias and lymphocytic leukemias. Nonlymphocytic leukemia generally involves the types of white blood cells (leukocytes) that are involved in engulfing, killing, and digesting bacteria and other parasites (phagocytosis) as well as releasing chemicals involved in allergic and immune responses. This type of leukemia may also involve erythroblastic cell types (immature red blood cells). Lymphocytic leukemia involves the lymphocyte type of white bloods cell that are responsible for the immune responses. Both nonlymphocytic and lymphocytic leukemia may, in turn, be separated into acute (rapid and fatal) and chronic (lingering, lasting) forms. For example; in acute myeloid leukemia (AML) there is diminished production of normal red blood cells (erythrocytes), granulocytes, and platelets (control clotting) which leads to death by anemia, infection, or hemorrhage. These events can be rapid. In chronic myeloid leukemia (CML) the leukemic cells retain the ability to differentiate (i.e., be responsive to stimulatory factors) and perform function; later there is a loss of the ability to respond. Leukemias, lymphomas, and other tumor types have been observed in experimental animals exposed to benzene by inhalation or oral administration. Exposure to benzene and/or its metabolites has also been linked with genetic changes in humans and animals (“IARC Monographs on the Evaluation of Cacinogenic Risk of Chemicals to Humans,” 1982, p. 345-389) and increased proliferation of mouse bone marrow cells (Irons, Stillman, Colagiovanni, & Henry, 1992). The occurrence of certain chromosomal changes in individuals with known exposure to benzene may serve as a marker for those at risk for contracting leukemia (Lumley, Barker, Murray, 1990).
The latest assessment by EPA places the excess risk of developing acute nonlymphocytic leukemia at 2.2 H 10-6 to 7.7 H 10-6/:g/m3. There is a risk of about two to eight excess acute nonlymphocytic leukemia cases in one million people exposed to 1:g/m3 over a lifetime (70 years) (“Carcinogenic Effects of Benzene: An Update,” 1998). This range of unit risk represents the maximum likelihood (MLE) estimate of risk, not an upper confidence limit (UCL).
A number of adverse noncancer health effects, blood disorders such as preleukemia and aplastic anemia, have also been associated with low-dose, long-term exposure to benzene (“Motor Vehicle-Related Air Toxics Study,” 1993). People with long-term exposure to benzene may experience harmful effects on the blood-forming tissues, especially the bone marrow. These effects can disrupt normal blood production and cause a decrease in important blood components, such as red blood cells and blood platelets, leading to anemia (a reduction in the number of red blood cells), leukopenia (a reduction in the number of white blood cells), or thrombocytopenia (a reduction in the number of blood platelets, thus reducing the ability for blood to clot). Chronic inhalation exposure to benzene in humans and animals results in pancytopenia. Pancytopenia is the reduction in the number of all three major types of blood cells (erythrocytes, or red blood cells, thrombocytes, or platelets, and leukocytes, or white blood cells). In adults, all three major types of blood cells are produced in the bone marrow of the vertebra, sternum, ribs, and pelvis. The bone marrow contains immature cells, known as multipotent myeloid stem cells, that later differentiate into the various mature blood cells. Pancytopenia results from a reduction in the ability of the red bone marrow to produce adequate numbers of these mature blood cells.a condition characterized by decreased numbers of circulating erythrocytes (red blood cells), leukocytes (white blood cells), and thrombocytes (blood platelets) (Aksoy, 1991 and Goldstein, 1988). Individuals that develop pancytopenia and have continued exposure to benzene may develop aplastic anemia. Aplastic anemia is a more severe blood disease and occurs when the bone marrow ceases to function, i.e.,these stem cells never reach maturity. The depression in bone marrow function occurs in two stages - hyperplasia, or increased synthesis of blood cell elements, followed by hypoplasia, or decreased synthesis. As the disease progresses, the bone marrow decreases functioning. This myeloplastic dysplasia (formation of abnormal tissue) without acute leukemiais known as preleukemia. The aplastic anemia can progress to AML (acute mylogenous leukemia). Others may exhibit both pancytopenia and bone marrow hyperplasia (excessive cell formation), a condition that may indicate a preleukemic state (Aksoy, Erdem, & DinCol, 1974 and Aksoy & Erdem, 1978). The most sensitive noncancer effect observed in humans is the depression of absolute lymphocyte counts in the circulating blood (Rothman, Li, Dosemeci, Bechtold, Marti, Wang, Linet, Xi, Lu, Smith, Titenko-Holland, Zhang, Blot, Yin, & Hayes, 1996).
2.7.5.2 Formaldehyde
Formaldehyde is the most prevalent aldehyde in vehicle exhaust. It is formed for incomplete combustion of both gasoline and diesel fuel and accounts for one to four percent of total exhaust TOG emissions, depending on control technology and fuel composition. It is not found in evaporative emissions.
Formaldehyde exhibits extremely complex atmospheric behavior (Ligocki, Whitten, Schulhof, Causley, & Smylie, 1991)It is formed by the atmospheric oxidation of virtually all organic species, including biogenic (produced by a living organism) hydrocarbons. Mobile sources contribute both primary formaldehyde (emitted directly from motor vehicles) and secondary formaldehyde (formed from photooxidation of other VOCs emitted from vehicles).
EPA has classified formaldehyde as a probable human carcinogen based on limited evidence for carcinogenicity in humans and sufficient evidence of carcinogenicity in animal studies, rats, mice, hamsters, and monkeys (“Assessment of health risks to garment workers,” 1987). Epidemiological studies in occupationally exposed workers suggest that long-term inhalation of formaldehyde may be associated with tumors of the nasopharyngeal cavity (generally the area at the back of the mouth near the nose), nasal cavity, and sinus. Studies in experimental animals provide sufficient evidence that long-term inhalation exposure to formaldehyde causes an increase in the incidence of squamous (epithelial) cell carcinomas (tumors) of the nasal cavity. The distribution of nasal tumors in rats suggests that not only regional exposure but also local tissue susceptibility may be important for the distribution of formaldehyde-induced tumors (“Motor Vehicle Air Toxics Health Information,” 1991). Research has demonstrated that formaldehyde produces mutagenic activity in cell cultures (“Motor Vehicle-Related Air Toxics Study,” 1993).
The MLE estimate of a lifetime extra cancer risk from continuous formaldehyde exposure is about 1.3 H 10-6/:g/m3. In other words, it is estimated that approximately 1 person in one million exposed to 1 :g/m3 formaldehyde continuously for their lifetime (70 years) would develop cancer as a result of this exposure.
Formaldehyde exposure also causes a range of noncancer health effects. At low concentrations (0.05-2.0 ppm), irritation of the eyes (tearing of the eyes and increased blinking) and mucous membranes is the principal effect observed in humans. At exposure to 1-11 ppm, other human upper respiratory effects associated with acute formaldehyde exposure include a dry or sore throat, and a tingling sensation of the nose. Sensitive individuals may experience these effects at lower concentrations. Forty percent of formaldehyde-producing factory workers reported nasal symptoms such as rhinitis (inflammation of the nasal membrane), nasal obstruction, and nasal discharge following chronic exposure (Wilhelmsson & Holmström, 1987). In persons with bronchial asthma, the upper respiratory irritation caused by formaldehyde can precipitate an acute asthmatic attack, sometimes at concentrations below 5 ppm (Burge, Harries, Lam, O’Brien, Patchett, 1985). Formaldehyde exposure may also cause bronchial asthma-like symptoms in nonasthmatics (Hendrick, Rando, Lane, & Morris, 1982 and Nordman, Keskinen, & Tuppurainen, 1985).
Immune stimulation may occur following formaldehyde exposure, although conclusive evidence is not available. Also, little is known about formaldehyde's effect on the central nervous system. Several animal inhalation studies have been conducted to assess the developmental toxicity of formaldehyde: The only exposure-related effect noted in these studies was decreased maternal body weight gain at the high-exposure level. No adverse effects on reproductive outcome of the fetuses that could be attributed to treatment were noted. An inhalation reference concentration (RfC), below which long-term exposures would not pose appreciable non-cancer health risks, is not available for formaldehyde at this time.
2.7.5.3 Acetaldehyde
Acetaldehyde is a saturated aldehyde that is found in vehicle exhaust and is formed as a result of incomplete combustion of both gasoline and diesel fuel. It is not a component of evaporative emissions. Acetaldehyde comprises 0.4 to 1.0 percent of exhaust TOG, depending on control technology and fuel composition (“Analysis of the Impacts of Control Programs on Motor Vehicle Toxics Emissions,” 1999).
The atmospheric chemistry of acetaldehyde is similar in many respects to that of formaldehyde (Ligocki et al., 1991). Like formaldehyde, it is produced and destroyed by atmospheric chemical transformation. Mobile sources contribute to ambient acetaldehyde levels both by their primary emissions and by secondary formation resulting from their VOC emissions. Acetaldehyde emissions are classified as a probable human carcinogen. The MLE estimate of a lifetime extra cancer risk from continuous acetaldehyde exposure is about 0.78 ? 10-6 /?g/m3. In other words, it is estimated that less than 1 person in one million exposed to 1 ?g/m3 acetaldehyde continuously for their lifetime (70 years) would develop cancer as a result of their exposure.
Non-cancer effects in studies with rats and mice showed acetaldehyde to be moderately toxic by the inhalation, oral, and intravenous routes (“Health Assessment Document for Acetaldehyde,” 1987 and “Preliminary Draft: Proposed identification of acetaldehyde as toxic air contaminant,” 1992 and “Acetaldehyde,” 1997). The primary acute effect of exposure to acetaldehyde vapors is irritation of the eyes, skin, and respiratory tract. At high concentrations, irritation and pulmonary effects can occur, which could facilitate the uptake of other contaminants. Little research exists that addresses the effects of inhalation of acetaldehyde on reproductive and developmental effects. The in vitro and in vivo studies provide evidence to suggest that acetaldehyde may be the causative factor in birth defects observed in fetal alcohol syndrome, though evidence is very limited linking these effects to inhalation exposure. Long-term exposures should be kept below the reference concentration of 9 ?g/m3 to avoid appreciable risk of these non-cancer health effects (“2,4-Dinitrophenol,” 1999).
2.7.5.4 1,3-Butadiene
1,3-Butadiene is formed in vehicle exhaust by the incomplete combustion of fuel. It is not present in vehicle evaporative emissions, because it is not present in any appreciable amount in fuel. 1,3-Butadiene accounts for 0.4 to 1.0 percent of total exhaust TOG, depending on control technology and fuel composition (“Analysis of the Impacts of Control Programs on Motor Vehicle Toxics Emissions,” 1999).
1,3-Butadiene was classified by EPA as a Group B2 (probable human) carcinogen in 1985 (“Mutagenicity and Carcingenicity Assessment of 1,3-Butadine,” 1985). This classification was based on evidence from two species of rodents and epidemiologic data. EPA recently prepared a draft assessment to determine if sufficient evidence exists to propose that 1,3-butadiene be classified as a known human carcinogen (“Health Assessment of 1,3-Butadiene,” 1998). However, the Environmental Health Committee of EPA’s Scientific Advisory Board (SAB), in reviewing the draft document, issued a majority opinion that 1,3-butadiene should instead be classified as a probable human carcinogen (“An SAB Report: Review of the Health Risk of 1,3 Butadiene,” 1998). The SAB panel recommended that EPA calculate the lifetime cancer risk estimates based on the human data from Delzell et al. (1995) and account for the highest exposure of “360 ppm-year” for 70 years. Based on this calculation (Koppikar, 1999) the maximum likelihood estimate of lifetime cancer risk from continuous 1,3-butadiene exposure is 2.21 ? 10-6/microgram/m3. This estimate implies that approximately 2 people in one million exposed to 1 microgram/m3 1,3-butadiene continuously for their lifetime (70 years) would develop cancer as a result of their exposure.
An adjustment factor of 3 can be applied to this potency estimate to reflect evidence from rodent studies suggesting that extrapolating the excess risk of leukemia in a male-only occupational cohort may underestimate the total cancer risk from 1,3-butadiene exposure in the general population (Koppikar, 2000). First, studies in both rats and mice indicate that 1,3-butadiene is a multi-site carcinogen. It is possible that humans exposed to 1,3-butadiene may also be at risk of cancers other than leukemia and that the epidemiologic study had insufficient power to detect excess cancer risks for other tissues or sites in the body. Second, both the rat and mouse studies suggest that females are more sensitive to 1,3-butadiene-induced carcinogenicity than males, and the female mammary gland was the only 1,3-butadiene-related tumor site common to both species. Use of a 3-fold adjustment to the potency estimate of 2.21 ? 10-6/microgram/m3 derived from the occupational epidemiologic study yields a upper bound cancer potency estimate of 1.4 ? 10-5/microgram/m3, which roughly corresponds to a combination of the human leukemia and mouse mammary gland tumor risk estimates, at least partially addressing the concerns that the leukemia risk estimated from the occupational data may underestimate total cancer risk to the general population, in particular females.
2.7.5.5 Acrolein
Acrolein is extremely toxic to humans from the inhalation route of exposure, with acute exposure resulting in upper respiratory tract irritation and congestion. The US EPA developed a reference concentration for inhalation (RfC) of acrolein of 0.02 micrograms/m3 1993. Although no information is available on its carcinogenic effects in humans, based on laboratory animal data, EPA considers acrolein a possible human carcinogen (“Acrolein,” 1993).
