Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants Volume 4 (2000) / Chapter Skim
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B4 Isoprene
B4 Isoprene
Pages 89-118
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From page 89... ...
Johnson Space Center Toxicology Group Medical Operations Branch Houston, Texas PHYSICAL AND CHEMICAL PROPERTIES Tsoprene is a colorless, highly volatile liquid or gas with a weak aromatic odor (TARC 1994~. Formula: Synonyms: CAS no.: Molecular weight: Boiling point: Melting point: Vapor pressure at 20°C: Conversion factors at 25°C: H2C=C(CH3~-CH=CH2 2-Methyl-1,3-butadiene (IUPAC)
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Industrially, isoprene is used to make isoprene rubber,which is used in vehicle tires; styrene block polymers, which are useful in adhesives; and busy! rubber, which is useful in lining hoses and tires to limit gas escape (TARC 1994~.
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~ 987~. As the exposure concentrations increased, the percentage of unchanged isoprene exhaled increased from 75% to 96% and the percentage inhaled and metabolized decreased from 25% to 4%.
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1987~. There are important species differences in the metabolism of inhaled isoprene in Fischer 344 (F344)
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1991~. As shown in Figure 4- 1, the epoxidation of isoprene occurs with preferential oxygen attack at the all-substituted carbon-carbon double bond.
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Exposed mice that recovered from narcosis were able to do better than control mice in a swin test administered 24 h later. White mice exposed for 40 min to a mean concentration of 2200 mg/m3 (790 ppm)
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1990~. Male Wistar rats exposed 4 hid for 30 ~ to isoprene vapor at a concentration of 0.36 ppm or 0.035 ppm showed variations in thymus cellularity and mitotic index (Mamadov 1979~.
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Epidemiological Data Three Russian epidemiological studies reported effects in workers associated with isoprene exposure in the isoprene rubber industry. Workers exposed to
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The confounding of exposures and the unknown concentrations prevent those data from being useful for setting limits. Similarly, isoprene rubber workers were reported to have excess fatigue, as measured by a photogenic reflex test, at the end of their work shift because of exposure to many organic compounds, including isoprene.
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From page 98... ...
No discernable effects were apparent in rats exposed for 13 w, and the change in rats after 26 w of exposure was limited to interstitial-cell hyperplasia in the testis ofthe 7000-ppm group. After a 26-w recovery of rats exposed for 26 w, rats in the 700-ppm and higher groups showed an increased incidence of interstitial-cell adenomas, with a very weak dose-response relationship (MeInick et al.
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The incidences ofthe lesions are given in Table 4-3. The dose-response relationship for olfactory epithelial degeneration in "recovered" mice suggests that this lesion is directly related to isoprene exposures; however, the dose-response curve for spinal-cord degeneration in recovered mice is difficult to understand in terms of isoprene exposures.
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The mouse data clearly show the carcinogenic potential of isoprene, although the dose-response relationship appears flat for liver and harderiangland tumors induced at concentrations above 220 ppm. The weight of evidence supports the hypothesis that isoprene induces cancer by mechanisms that are threshold in nature.
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101 au o D au o o Lo U)
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For example, the authors concluded that "a threshold effect level and strong nonTinearities with respect to concentration appeared to exist for tumor development." Statistical analysis of the tumor incidence data to test the applicability of the equivaTent-dosemetric hypothesis indicated that that concept was not applicable for isoprene carcinogenesis in mice (Cox et al.
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Carcinogenic activity caused by an aneugen could have a Tow-concentration threshold for cancer induction and might also show a plateau at high concentrations where spindle destruction occurs. Developmental Toxicity An inhalation developmental study has been reported in Swiss (CD-~)
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Interactions with Other Chemicals No reports of interactions of isoprene with other chemicals were found. A summary of the toxicity data on isoprene is presented in Table 4-5.
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105 Cal x C)
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IARC 1994 STEL, short-term exposure limit. TABLE 4-7 Spacecraft Maximum Allowable Concentrations Concentration, Concentration, Duration ppm mg/m3 Target Toxicity 1 h 50 140 Mucosal irritation 24h 25 70 Mucosal irritation 7 da 2 6 Anemia, mucosal irritation 30 ~2 6 Anemia, mucosal irritation 180 ~1 3 Anemia, respiratory-system injury, neurotoxicity Previous 7-d SMAC = 200 ppm (560 mg/m3~.
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From page 108... ...
No details of the test method, controT method, or statistical analyses were given, so these reported findings are not suitable for setting limits for acute neurotoxicity. Mucosal Irritation In the Gostinskii report, 10 human subjects experienced sTight mucosal irritation when exposed to isoprene at 160 mg/m3 (57 ppm)
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, or 6 ppm. Time factors were not applied, because mucosal irritation generally is experienced only in the first few minutes of exposure untiT adaptation occurs, and the 1 O-fold factor applied to the LOAEL is conservative.
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(1994) described an anemia in mice resulting from isoprene exposures that was initially (3 d)
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These effects were not mentioned in male mice exposed for 26 w and recovered for 26 w; however, liver tumors were significantly increased in exposed mice when compared with control mice at exposures of 700 ppm or more (Table 4-4~. The NOAEL for such tumors was 220 ppm.
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Respiratory-System Injury Olfactory degeneration and lung tumors have been associated with isoprene exposures in mate mice (Tables 4-l, 4-2, 4-3, and 4-4~. Again, the data are perplexing because the lowest concentration that induced olfactory degeneration for 2-w exposures was between 1750 and 3500 ppm (Table Ill)
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Endogenous Production of Isoprene For systemic effects such as neurotoxicity, it would be illogical to set an acceptable exposure concentration for isoprene that would lead to an uptake rate much below the endogenous production rate. According to an abstract, the endogenous production rate for isoprene in humans is 0.15 ,umol/(kg~h)
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114 en o .
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_1 o By · - ~ Gil ~ cot o ~ 'e , 'v ^ =~ c)
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MA CS FOR * ELECTED AIRBORNE CONTAMINANTS RECOMMENDATIONS The isoprene exposure limits proposed may be extremely conservative because they were based on the most susceptible species, mice.
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1990. Pharmacokinetics and endogenous production of isoprene in humans.
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1992. Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants.
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