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EC number: 309-713-4 | CAS number: 100684-40-0 A complex combination of hydrocarbons obtained as a residue from the distillation of crude oil under vacuum. It consists predominantly of hydrocarbons having carbon numbers predominantly in the range above C50 and boiling in the range above approximately 500°C (932°F).
Table 1. Non-neoplastic lesions of the respiratory tract
Nasal and paranasal cavities
Olfactory epithelial basal cell hyperplasia
Respiratory epithelial hyperplasia
Mucous (goblet) cell hyperplasia
Olfactory epithelial eosinophilic cytoplasmic inclusion(s)
Respiratory epithelial eosinophilic cytoplasmic inclusion(s)
Mucosal mononuclear/inflammatory cell infiltration
Bronchiolo-alveolar hyperplasia, bronchiolar type
Mononuclear/inflammatory cell infiltration
Lung associated lymph nodes
Accumulation of foamy macrophages (histiocytosis)
Significantly different from the control * p<0.05; ** p<0.01, *** p<0.001
Read across for the key inhalation studies is justified because fumes of semi-blown bitumen have been shown to be comparable with fumes of straight-run paving bitumen. In a comparative analytical study, fumes from a straight-run and a semi-blown bitumen were closely similar in terms of composition and physical properties.
A two-year bioassay with fumes from bitumen was conducted in Wistar rats (Crl:WI(WU)BR). The animals, 50 males and 50 females per dose group, were exposed nose-only to fumes regenerated from the bitumen fume condensate at target concentrations of 0 (clean air), 4, 20 and 100 mg/m3 total hydrocarbon concentration for 6 h/day, 5 days/week for 104 weeks. These concentrations were chosen based on a series of range-finding experiments in which the animals at the highest dose showed signs of slight respiratory irritation. The mean actual concentrations in the study, measured as total hydrocarbon (THC, sum of aerosol and vapour), were 0, 4.1±0.3, 20.7±1.8, and 103.9±9.7 mg/m3 using the methodology described by BIA (Berufsgenossenschaftliches Institut fuer). (Note: taking into account the conversion factor of 1.66 between the absolute concentration of fumes from bitumen and the concentration measured with this method, the concentrations were 0, 6.8 mg/m3, 34.4 mg/m3, and 172.5 mg/m3, respectively.) Additional control animals (36) and animals exposed to the high dose (36) were included in the study to conduct bronchio-alveolar lavage (BAL) and to investigate proliferation of respiratory epithelia, at 7 days, 90 days and 12 months following the start of exposure. In the main study, no statistically significant differences in mortality incidence were observed among the various groups: the mortality prior to final sacrifice was 10, 18, 16 and 14% in the males and 28, 12, 16 and 22% in the females for the control, low, medium and high dose groups, respectively. A statistically significant reduction of body weight gain was observed in the medium dose groups from day 119 (males and females) and in the high dose groups as of day 21 (males) or day 28 (females). The difference at sacrifice averaged –3% (males) and –8% (females) of the medium dose group and –7% (males) and –8% (females) in the high dose group.
Lactic dehydrogenase activity in BAL fluid, indicating an increased permeability of cell membranes, was slightly elevated in the exposed females (but not males). However, the absolute values were low and below the values of historical controls and were considered of minor relevance by the investigators.g-Glutamyltransferase levels in BAL fluid, indicative of increased phagocytitic activity of macrophages, were slightly increased in both males and females. Overall results of BAL investigations showed that effects, if any, were very slight to slight. The authors conclude that the broncheoalveolar region of the respiratory tract is not significantly impacted by exposure to bitumen fume. Unit Length Labeling Index was comparable in lung parenchyma of treated and control animals. No consistent effects on cell proliferation were seen for level 1 respiratory epithelium, level 1 non-ciliated epithelium and level 3 olfactory epithelium. The only consistent increase in proliferation was seen in the transitional zone of respiratory to olfactory epithelium in the exposed males, but not females. At the mid-dose level (20.7 mg/m3) the full histopathology at the termination of the study after 2 years of exposure showed some slight effects in the nasal passages. In particular hyperplasia of mucous cells (goblet cells) and eosinophilic cytoplasmic inclusions in the olfactory epithelium was observed. In addition, a statistically significant increased incidence of mononuclear cell infiltrates was seen in the epithelium of the nasal and paranasal cavities in animals of the mid- and high-dose groups. These effects were also seen at a lower incidence in the animals of the control and low-dose groups and are probably adaptive in nature.
The NOAEL for systemic effects following inhalation was 103.9 mg/m3(172.5 mg/m3adjusted) based on the absence of any histopathological changes or alterations in clinical chemistry or haematology. The LOEC for local effects was 20.7 mg/m³ (34.4 mg/m³ adjusted), based on the effects on the nasal passages. The NOAEC was set at half the LOAEC, that is 10.4 mg/m³ total hydrocarbon concentration (17.2 mg/m³ adjusted) based on the minimal effects and the facts that in the 90-day study and the reproductive toxicity screening studies NOAECs of 20.1 mg/m³ (30.4 mg/m³ adjusted) and 30 mg/m3were found, respectively.
This study received a Klimisch score of one and is classified as reliable without restrictions because it was an acceptable study that was well documented.
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