Priority Substances List Assessment Report - 1,3-Butadiene

2.0 Summary of Information Critical to Assessment of "Toxic"under CEPA 1999 (continued)

2.4 Effects characterization

2.4.4 Toxicokinetics and metabolism

2.4.4.4 Genotoxicity

The potential genotoxicity of butadiene has recently been investigated in several studies of groups of workers exposed in the production of butadiene, styrene-butadiene rubber or polybutadiene rubber. Although the data available to date are not completely consistent, they indicate that there is some evidence that exposure to butadiene induces genetic effects in occupationally exposed populations and that sensitivity to the induction of these effects is related to genetic polymorphism for enzymes involved in the metabolism of butadiene, most notably those within the glutathione-S-transferase class. The results of several in vitro studies in human lymphocytes have demonstrated that sensitivity to DEB-induced sister chromatid exchanges and micronuclei is associated with the presence or absence of homozygous deletion of the GSTT1 gene, which codes for GSTΘ (Kelsey et al. 1995; Norppa et al. 1995; Wiencke et al. 1995; Landi et al. 1996; Pelin et al. 1996; Vlachodimitropoulos et al. 1997). Similarly, sensitivity to sister chromatid exchanges induced by EB appears to be related to genotype for GSTM1, which codes for GSTµ (Wiencke and Kelsey, 1993; Uuskula et al. 1995), and possibly also GSTT1 genotype in GSTM1-null individuals (Bernardini et al. 1998). However, there were no differences in sensitivity to sister chromatid exchanges induced by EBdiol in individuals with and without deletions for GSTT1 or GSTM1 (Bernardini et al. 1996).

Although no increased frequencies of sister chromatid exchanges, chromosomal aberrations or micronuclei were observed in earlier studies in butadiene production workers in Portugal and the Czech Republic compared with controls (Sorsa et al. 1994, 1996b), positive results for chromosomal aberrations and sister chromatid exchanges were obtained in the most recent study of the Czech workers (Tates et al. 1996; Srám et al. 1998). When genotype was considered, there was a significant increase in the frequency of chromosomal aberrations in both exposed and control subjects from both plants who were deficient for the GSTT1 gene (Sorsa et al. 1996a).

An increased frequency of hprt - mutants in peripheral blood lymphocytes has been observed in two studies of exposed workers at a butadiene production facility in Texas (Legator et al. 1993; Ward et al. 1994; Au et al. 1995) and in preliminary results of a study of styrenebutadiene rubber workers from the same region (J.B. Ward et al. 1996; Ward, 1997a). Although analyses by genotype are not yet available, it was noted that the highest frequency of hprt - variants occurred in an individual who was GSTT1 null. In contrast to the observations in the Texan plants, however, no increase in hprt - mutant frequency was observed in workers exposed to similar levels of butadiene at the monomer plant in the Czech Republic (Tates et al. 1996) or in a population of polybutadiene rubber workers in China (Hayes et al. 1996) (no information on genotype was presented). These investigations involved different analytical methodologies (autoradiographic versus clonal assays), which may account for the discordance in the results; in addition, differences in occupational scenarios, exposure levels, age, smoking habits or other lifestyle factors may have contributed to the discrepancy. Current ongoing research (including genotyping) may explain the differences in the results.

Decreased DNA repair ability was also observed in peripheral blood lymphocytes of exposed workers at the monomer production and styrene-butadiene rubber facilities in Texas in both a γ-radiation challenge assay and a CAT-Host Cell Reactivation assay (Hallberg et al. 1997; Ward, 1997b). However, the difference between exposed and "unexposed" monomer workers in the response to the challenge assay was no longer significant after ambient levels in the plant were reduced. Similarly, the effect on DNA repair ability in styrene-butadiene rubber workers was less when only non-smokers were considered.

The detection of alkylated DNA (the same adduct as detected in the liver of mice and rats exposed to butadiene; Jelitto et al. 1989; Koivisto et al. 1997) in the urine of an exposed worker (Peltonen et al. 1993) also provides some evidence of the interaction of butadiene or its metabolites with genetic material in humans.

2.4.5 Abiotic atmospheric effects

The potential for butadiene to contribute to the depletion of stratospheric ozone, to global warming or to formation of ground-level ozone was examined.

Since butadiene is not a halogenated compound, its Ozone Depletion Potential (ODP) is 0, and it will therefore not contribute to the depletion of stratospheric ozone (Bunce, 1996).

Gases involved in global warming strongly absorb infrared radiation of wavelengths between 7 and 13 µm, enabling them to trap and re-radiate the Earth's thermal radiation (Wang et al. 1976; Ramanathan et al. 1985). Worst-case calculations were made to determine if butadiene has the potential to contribute to climate change (Bunce, 1996), assuming it has the same infrared absorption strength as the reference compound CFC-11. The Global Warming Potential (GWP) was calculated to be 2.5 × 10^-5 (relative to the reference compound CFC-11, where GWP for CFC-11 = 1), based on the following formula:

GWP = (t_butadiene/t_CFC^-11) × (M_CFC^-11/M_butadiene) × (S_butadiene /S_CFC^-11)

where:

• t_butadiene = lifetime of butadiene = 5.9 · 10^-4 years
• t_CFC-11 = lifetime of CFC-11 = 60 years
• M_CFC-11 = molecular weight of CFC-11 = 137.5 g/mol
• M_butadiene = molecular weight of butadiene = 54 g/mol
• S_butadiene = infrared absorption strength of butadiene = 2389 cm^-2 atm^-1 (worst case)
• S_CFC-11 = infrared absorption strength of CFC-11 = 2389 cm^-2 atm^-1

Since this estimate for the GWP is much less than 1% of that of the reference compound, butadiene is not considered to be involved in climate change (Bunce, 1996).

The contribution of VOCs to the formation of ground-level ozone and the resulting contribution to smog formation is a complex process and has been studied extensively. The terms reactivity, incremental reactivity and photochemical ozone formation potential denote the ability of an organic compound in the atmosphere to influence the formation of ozone (Paraskevopoulos et al. 1995). Estimates of reactivity of a substance depend on the definition and method of calculation of the reactivity, the VOC/NOx ratio, the age of the air mass, the chemical mechanisms in the model, the chemical composition of the hydrocarbon mixture into which the VOC is emitted, the geographical and meteorological conditions of the airshed of interest (including temperature and intensity and quality of light), and the extent of dilution (Paraskevopoulos et al. 1995).

The Photochemical Ozone Creation Potential (POCP) is one of the simpler indices of the potential contribution of an organic compound to the formation of ground-level ozone, based on the rate of reaction of the substance with the hydroxyl radical relative to ethene (CEU, 1995). Ethene, a chemical that is considered to be important in ozone formation, has an assigned POCP value of 100. The POCP for butadiene was estimated to be 407 relative to ethene, using the following formula (Bunce, 1996):

POCP = (k_butadiene /k_ethene) × (M_ethene /M_butadiene) × 100

where:

• k_butadiene is the rate constant for the reaction of butadiene with OH radicals (6.68 × 10^-11 cm³/mol per second),
• k_ethene is the rate constant for the reaction of ethene with OH radicals (8.5 × 10^-12 cm³/mol per second),
• M_ethene is the molecular weight of ethene (28.1 g/mol), and
• M_butadiene is the molecular weight of butadiene (54 g/mol).

Because of its high reactivity, butadiene will be particularly important to photochemical ozone formation close to its sources of release. As it moves away from these sources, butadiene reacts with both hydroxyl radicals and ozone to form products such as formaldehyde, which are also active in the photochemical formation of ozone.

Various published reactivity values for butadiene and other selected VOCs are presented by Paraskevopoulos et al. (1995). The use of a maximum incremental reactivity (MIR) scale has been recommended by Carter (1994) as optimal when applied to the wide variety of conditions where ozone is sensitive to VOCs, being fairly robust to the choices of scenarios used to derive it.

Recently, butadiene was one of the VOCs identified in the Canadian 1996 NOx/VOC Science Assessment as part of the Multi- Stakeholder NOx/VOC Science Program (Dann and Summers, 1997). Based on air measurements taken at nine urban and suburban sites in Canada from June to August from 1989 to 1993, butadiene was ranked 60th of the most abundant non-methane hydrocarbon and carbonyl species. Based on these measurements and on an MIR value of approximately 10 mol ozone/mol carbon, butadiene represented approximately 0.9% of the total volatile organic carbon reactivity and was ranked 26th when sorted by the total volatile organic carbon reactivities. Total volatile organic carbon reactivity denotes the ability of organic compounds to contribute to the formation of ozone.

Therefore, because of its high reactivity and moderate concentrations encountered in Canada, butadiene plays a role in the photochemical formation of ground-level ozone.