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Administrative data

Link to relevant study record(s)

Description of key information

No experimental information is available on the toxicokinetic behaviour of the streams comprising this category, however the members of this category are gases indicating that uptake via the dermal and oral routes will be negligible. Absorption after inhalation exposure is assumed to be 100%. No measured information is available on bioconcentration potential of these streams, however a log Kow < 4.5 indicates a low potential for bioaccumulation.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - inhalation (%):

Additional information

There are no specific studies on the streams in the C4, low 1,3 -butadiene category (CAS Numbers; 91052-98-1, 92045-23-3, 95465-89-7, 95465-90-0 and 95465-91-1) but data are available on the component substances.


Dahl et al (1988) investigated the comparative rates of uptake of 19 hydrocarbon vapours by rats. Representative compounds from the chemical classes of alkenes, alkynes, straight-chain and branched alkanes, alicyclics, and aromatics were examined. It was concluded that absorption tends to increase with molecular weight, so that straight chain molecules are more highly absorbed than branched isomers, and aromatic molecules are more highly absorbed than paraffins. Thus short chain C1-C4 alkanes which exist as a vapour at room temperature, are very poorly absorbed, and if absorbed, are normally rapidly exhaled. Isobutane absorption following inhalation exposure is low (uptake 0.6 -1.0 nmol/kg/min/ppm, lower than butane). Butane absorption following inhalation exposure at 100ppm (240 mg/m3) is low (uptake 1.5 -1.8 nmol/kg/min/ppm) or 0.09 -0.1 micrograms/kg/min/ppm). From this the Health Council of the Netherlands (2004) calculated that approximately 10% is absorbed.


Unsaturated compounds are absorbed better than saturated ones (Dahl, 1988), this is supported by the butenes database. Members of the butenes category are absorbed, widely distributed metabolised and excreted in rats and mice (Eide et al, 1995).Rats exposed to 300 ppm (688 mg/m3) of 1-alkenes (from C2-C8, including 1-butene) for 12h per day for 3 days had increased concentrations of the alkenes in blood and tissues, proportional to increasing numbers of carbon atoms. In contrast, levels of haemoglobin and DNA adducts decreased with increasing numbers of carbon atoms. The 1-alkenes were widely distributed within the body with the lowest concentrations in blood and the highest in fat.


More extensive metabolism and distribution studies have been carried out on the butene isomer, 2-methylpropene (isobutene). A higher rate of metabolism in the mouse and saturation of metabolism in rats and mice have been demonstrated in vivo by Csanady et al (1991) and Henderson et al (1993). In the study of Csanady et al (1991), rats and mice were exposed to 2-methylpropene, at concentrations up to 500 ppm (1147 mg/m3), metabolic elimination was first order. The maximal metabolic elimination rates were 340 µmol/kg/h for rats and 560 µmol/kg/h for mice. The atmospheric concentration at which Vmax/2 was reached was 1200 ppm (2754 mg/m3) for rats and 1800 ppm (4131 mg/m3) for mice. The metabolism was saturable in both species and was blocked by inhibitors of P450 enzymes. In the study of Henderson et al (1993), rats were exposed to 2-methylpropene at concentrations from 40 to 4000 ppm (91.8-9180 mg/m3). Rapid metabolism to oxidised metabolites excreted in the urine occurred and isobutenediol and 2-hydroxyisobutyric acid were identified as metabolites. Blood levels of 2-methylpropene were linearly related to exposure up to 400ppm (918 mg/m3) but were supralinear at 4000 ppm (9180 mg/m3) indicating saturation of metabolism at this higher dose level.


Similar findings were reported during a carcinogenicity study on 2-methylpropene (NTP, 1988). The major urinary metabolite of 2-methylpropene (2-hydroxyisobutyric acid: HIBA) was measured in the urine of rats and mice as an indicator of exposure. F344/N rats and B6C3F1 mice were exposed to 2-methylpropene at concentrations of 0, 500, 2,000 or 8,000 ppm, (1147, 4589, 18,359 mg/m3) for 105 weeks. In both species, the amount excreted increased with increasing exposure concentration but when HIBA concentration was normalized to isobutene exposure concentration, the relative amount of HIBA excreted decreased with increasing exposure concentration, implying nonlinear kinetics (NTP, 1988).


The in vivo metabolism studies are supported by extensive in vitro metabolism studies. Cornet et al (1991) showed that 2-methylpropene was metabolised to its epoxide 2-methyl-1,2-epoxypropane in a mouse liver in vitro system. The epoxide was rapidly further metabolised by epoxide hydrolase to methyl-1,2-propanediol and by glutathione-S-transferase to the glutathione conjugate. Further studies (Cornet et al, 1995) using in vitro rat, mouse and human liver systems demonstrated that the lowest rates of biotransformation to the epoxide metabolite were found in human liver, followed by rat then mouse. Quantification of levels of epoxide hydrolase, the major enzyme responsible for the detoxification of the epoxide, in these species revealed that human liver has the highest level followed by rats then mice. In contrast, levels of P450 were lowest in humans. These results demonstrate a clear species difference in the metabolism of 2-methylpropene and suggest that mice and rats are not good models for the metabolism of 2-methylpropene in species where concentrations of the primary epoxide metabolite are likely to be lower than in these rodent species.