Acute Exposure Guideline Levels for Selected Airborne Chemicals Volume 14 (2013) / Chapter Skim
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3 n-Hexane Acute Exposure Guideline Levels
3 n-Hexane Acute Exposure Guideline Levels
Pages 66-114
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From page 66... ...
Both the document and the AEGL values were then reviewed by the National Research Council (NRC) Committee on Acute Exposure Guideline Levels.
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From page 67... ...
Visible signs of acute toxicity from n-hexane are generally associated with effects on the nervous system, such as reduced respiration, ptosis, myoclonic seizures, ataxia, decreased motor activity, sedation, laying
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From page 68... ...
. Although the study focused on blood n-hexane concentrations, some toxicity data were provided; rats exposed for 25 or 30 min showed visible signs of toxicity (ataxia and decreased motor activity)
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From page 69... ...
c The AEGL-3 values for the 30-min, 1-h, 4-h, and 8-h durations are each 8,600 ppm (30,000 mg/m3) , which is higher than 50% of the lower explosive limit of n-hexane in air of 1.1% (11,000 ppm)
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From page 70... ...
2006 Vapor pressure 138 mm Hg @ 24°C; WHO 1991; 150 mm Hg @ 25°C ATSDR 1999 Flammability Highly flammable ATSDR 1999 Explosive Lower explosive limit = 1.1% WHO 1991 3 Conversion factors 1 mg/m = 0.284 ppm WHO 1991 1 ppm = 3.52 mg/m3 Commercial hexanes are manufactured by two-tower distillation of a suitable hydrocarbon feedstock (WHO 1991)
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From page 71... ...
Since most of the studies concern repeated exposure to solvents with a low percentage of n-hexane (not pure) , they were considered of little or no relevance for deriving AEGL values for n-hexane are not discussed in detail.
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From page 72... ...
No adverse clinical effects or subjective complaints were also reported in healthy male volunteers (19- to 26-years old) exposed twice (nose only; in a sitting position)
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From page 73... ...
No adverse clinical effects were also reported in four healthy shoe factory workers (women, 41-54 years old) exposed during four working days to a mean concentration of n-hexane in the breathing zone of 1.9-31 ppm (6.7-108.7 mg/m3)
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From page 74... ...
Only a negative unscheduled DNA synthesis assay using human lymphocytes has been reported. Although genotoxic effects have not been examined in humans after n-hexane exposure, genotoxicity in humans cannot be excluded because some positive results were reported in limited animal studies (polyploidy, structural aberrations, and sister chromatid exchanges in in vitro tests with mammalian cells, and morphologic alterations in sperm and chromatid breaks in bone marrow cells in studies of rats)
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From page 75... ...
This study could not be used for quantitative analysis, because mice were exposed in a closed system and n-hexane concentration as well as the oxygen concentration will have decreased during exposure while carbon dioxide will have increased; the number of animals exposed at each exposure concentration was unknown; and respiration rate steadily decreased during exposure.
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From page 76... ...
At 64,000 ppm, all mice had respiratory arrest within 4.5 min. During exposure at 64,000 ppm, respiration was highly irregular; excitation was followed by light anesthesia with body movements, irregular respiration, an increase in inspiratory effort, and a decrease in the expiratory effort.
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From page 77... ...
1974 64,000 <4.5 min Lethality a Initial concentration in a closed system. Concentrations were continuously monitored and were within 10% of the target concentrations.
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for 8 h to n-hexane (purity not specified) at nominal concentrations of 0 and 4,000 ppm (no monitoring of actual concentrations during exposure)
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From page 79... ...
Rats exposed to n-hexane showed some symptoms including sedation, hypothermia, and ptosis. The incidence and severity of symptoms were dependent on exposure concentration.
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From page 80... ...
(1984) were considered irrelevant for deriving AEGL values.
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From page 81... ...
Although the study focused on blood n-hexane concentrations, it was mentioned that only the animals exposed for 25 and 30 min showed visible signs of toxicity (ataxia and decreased motor activity)
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From page 82... ...
During exposure, respiration was highly irregular; excitation was followed by light anesthesia with body movements, irregular respiration, an increase in inspiratory effort, and a decrease in the expiratory effort. Respiratory arrest occurred at the end of inspiration.
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From page 83... ...
However, no data were identified to evaluate the potential for peripheral neuropathy to occur following exposure to a single high dose of n-hexane. Many studies reviewed in Section 3.2 (Animal Toxicity Data, Nonlethal Toxicity)
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From page 84... ...
This effect was more pronounced in animals exposed during gestation and postnatally. Furthermore, a delay in the maturation of cerebellar cortex was observed (fissura prima of the vermis cerebella; delay in migration of the outer granular cells and a persistence of Purkinje cells)
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From page 85... ...
nHexane was also negative in an in vitro test for induction of chromosome loss in Saccharomyces cerevisiae. Negative results for chromosomal aberrations, sister chromatid exchanges, and point mutation rate were generally also obtained in mammalian cells except for one observation of polyploidy in Chinese hamster lung (CHL)
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From page 86... ...
Chromatid breaks were reported in rat bone marrow cells (concentration and exposure duration not specified)
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From page 87... ...
could not be used for quantitative analysis because mice were exposed in a static system, the number of animals per exposure concentration was unknown, and respiration rate steadily decreased during exposure. Exposure for 5 min to n-hexane at 16,000 ppm caused light anesthesia in mice.
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From page 88... ...
n-Hexane was found to be not mutagenic in a dominant lethal test, micronucleus test, and sperm morphology test with mice. In rats, however, morphologic alterations in sperm and chromatid breaks in bone marrow cells were observed.
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From page 89... ...
n-Hexane concentrations were measured in inhaled and exhaled air. Physical exercise during exposure caused an important increase in lung clearance values from 2.30 L/min at rest to 5.36 L/min at 80 W of peak exercise.
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From page 90... ...
n-Hexane metabolites in rat blood were 2-hexanol, methyl-n-butyl ketone, 2,5dimethylfuran, and 2,5-HD. Humans chronically exposed to a mixture of hexane isomers containing n-hexane at 10-40 ppm had urinary concentrations of 2,5-HD ranging from 0.4 to 21.7 mg/L, which is the same proportion as rats exposed once to n-hexane at 5,000 ppm for 6 h (1.7 mg/L)
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From page 91... ...
Lower concentrations were found in a second series of experiments with rats exposed at 24,500 or 46,100 ppm for 10 min. Blood concentrations of n-hexane immediately after exposure were approximately 4 and 8 µg/mL, respectively, and corresponding brain concentrations were less than 20 and approximately 40 µg/g.
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From page 92... ...
In male Fischer-344 rats exposed to n-hexane (purity 95.8%) at 500, 1,000, 3,000, and 10,000 ppm for 6 h, steady-state n-hexane concentrations were achieved within 30 min in blood and within 2 h in all other tissues examined (brain, liver, kidneys, lungs, testes, and sciatic nerve)
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From page 93... ...
. Analysis of the urine of male Wistar rats exposed (whole body)
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From page 94... ...
Steady-state n-hexane concentrations in blood are rapidly reached in approximately 30 min. Physical exercise resulted in an increase in lung clearance values, a decrease in alveolar retention, and an increase in blood n-hexane concentration.
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From page 95... ...
Excretion of metabolites was linearly dependent on the exposure concentration of n-hexane to about 300 ppm; above 300 ppm, saturation kinetics occurred.
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From page 96... ...
report whether the operators were exposed to n-hexane vapor or solutions of n-hexane. Respiratory Tract Irritation Several effects on the lungs of laboratory animals have been reported following acute exposure to n-hexane.
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From page 97... ...
Male volunteers exposed to n-hexane at 54 ppm for 2 h during light physical exercise did not experience any signs of discomfort. Toxicokinetic studies of n-hexane with volunteers included exposures up to 200 ppm for 4 h at rest and up to 100 ppm for 3 h under increasing levels of exercise (Veulemans et al.
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From page 98... ...
When such effects occurred was not reported but this statement might indicate that 48,000 ppm can cause myoclonic seizures in rats. A kinetic study reported that no visible signs of toxicity were observed in rats exposed to n-hexane at 86,222 ppm for up to 20 min, but that ataxia and decreased motor activity was observed in rats exposed for 25 or 30 min (Raje et al.
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From page 99... ...
A kinetic study reported that no visible signs of toxicity were seen in rats exposed to n-hexane at 86,222 ppm for up to 20 min; ataxia and decreased motor activity was reported in rats exposed for 25 or 30 min (Raje et al.
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From page 100... ...
Adequate human data addressing the level of effects defined by the AEGL-2 were not available. Because of reporting insufficiencies in studies with rats and confounding methologic issues in studies with mice, there is considerable uncertainty regarding the no-effect level for AEGL-2 level effects.
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From page 101... ...
In that study, no deaths occurred in rats exposed to n-hexane at 86,222 ppm for 30 min. A total uncertainty factor of 10 was applied; a factor of 3 for interspecies differences and a factor for 3 for intraspecies variability.
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From page 102... ...
8.3. Data Quality and Research Needs An adequate acute toxicity study on n-hexane is lacking, and the available data do not provide a strong basis for AEGL values.
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From page 103... ...
TABLE 3-8 AEGL Values for n-Hexane Classification 10 min 30 min 1h 4h 8h AEGL-1 NR NR NR NR NR (nondisabling) AEGL-2 4,000 ppma 2,900 ppma 2,900 ppma 2,900 ppma 2,900 ppma (disabling)
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e TLV-TWA (threshold limit value - time weighted average, American Conference of Governmental Industrial Hygienists)
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9. REFERENCES ACGIH (American Conference of Governmental Industrial Hygienists)
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1989. Thirteen week toxicity study of n-hexane in B6C3F1 mice after inhalation exposure.
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From page 107... ...
Pp. 13-47 in Acute Exposure Guideline Levels for Selected Airborne Chemicals, Vol.
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From page 108... ...
1984. Blood n-hexane concentration following acute inhalation exposure in rats.
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From page 109... ...
1984. Blood n hexane concentration following acute inhalation exposure in rats.
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From page 110... ...
110 Acute Exposure Guideline Levels Therefore, AEGL-2 values for the 1-h, 4-h, and 8-h durations were set equal to the 30-min AEGL-2 value. Uncertainty factors: 3 for interspecies differences 3 for intraspecies variability 10-min AEGL-3: C3 × 10 min = 19.08 × 1012 ppm-min C ≈ 12,000 ppm (42,000 mg/m3)
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From page 111... ...
. TABLE B-1 Data Used in Category Plot Source Species Sex No.
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From page 112... ...
1982 Human Male 1 200 240 0 van Engelen et al. 1997 Human Male 1 60 15.5 0 Human Male 1 60 234.6 0 Bus et al.
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From page 113... ...
1984. Blood n hexane concentration following acute inhalation exposure in rats.
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From page 114... ...
Mortality from n-hexane exposure is preceded by CNS depression, and variation in susceptibility for CNS-depressing effects is not very great in the human population. Modifying factor: None Animal-to-human dosimetric adjustment: Not applicable Time scaling: Because a steady-state blood concentration will be reached within 30 min of exposure, no increase in effect-size by exposure duration is expected from 30 min to 8 h.
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