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EC number: 203-628-5 | CAS number: 108-90-7
Short description of key information on bioaccumulation potential result: Chlorobenzene can be absorbed via the lung or the gastrointestinal tract. Suitable studies for evaluating the percutaneous uptake are not available.As the compound is a lipophilic substance, its distribution in the organism is essentially dependent on the fat content of individual organs.Chlorobenzene is eliminated in the form of metabolites, principally in the urine and to a smaller extent in the faeces as well. Unmetabolized chlorobenzene is mainly exhaled via the lungs. Moreover, it could be demonstrated, that the metabolism of chlorobenzene is saturated at repeated at high doses.
Male Sprague-Dawly rats were exposed for 8 hr/day to 100, 400, or 700 ppm of [14C]-chlorobenzene vapor for either 1 day or 5 days. The study was conducted according to OECD guideline 417 with deviations (Only characterization instead of identification of the metabolites. Analytical purity not reported). 6 rats of each group were exposed for 5 consecutive days (multiple exposure regimen). Another 3 rats were exposed for the first 4 days of the multiple exposure regimen, but were sacrificed after 16 hr their final exposure. The other 6 rats were exposed only on the fifth day on each exposure block (single exposure regimen). Another group of 12 rats was exposed in a 1-day repeated study at 400 ppm to account for the statistical signifcance of blocking effect (Sullivan et al 1983).
Immediataley after the fifth day of exposure, 6 of the 12 remaining rats (3 singly exposed and 3 multiply exposed) were placed in metabolism cages for collection of urine and expired material. The other 6 rats were sacrificed 48 hr after exposure for assessment of remaining tissue burdens.
There was no evidence of accumulation in the rats sacrificed immediately after exposure, except in kidney (single exposure 0hr vs multiple exposure 0 -hr). There was a tendency at the 48 hrs after exposure, for mutiply exposed rats to exhibit higher tissue burdens than rats exposed only once. The [14C]chlorobenzene of adipose tissue increased about 8 to 10 fold when the concentration was increased from 100 ppm (469 mg/m³) to 400 ppm (1871 mg/m³) and about 3 to 5 fold from 400 ppm (1871 mg/m³) to 700 ppm (3275 mg/m³).
Respiratory elimination of [14C]chlorobenzene also increased in a dose-dependent way. There are no differences due to dosing regimen in the amount of material excreted in the urine. There was a significant difference in the amount of 14 C-chlorobenzene expired between the two 400 ppm (1871 mg/m³), singly exposed groups of rats, with the rats of the repeat study expiring more than rats in the initial group.
The exposure regimen effect was significant only at the 700 ppm concentration (3275 mg/m³), with multiply exposed rats yielding a shorter fast phase t1/2 than singly exposed rats. There was no signifcant effect of concentration on respiratory elimination between the 100- and 400 ppm (469 -and 1871-mg/m³) groups . However, the fast phase half-lives of the 700 ppm rats were longer than those observed at lower exposure concentrations.
Analysis of treatment effects in the metabolite profile was based on the percentage of mercapturic acid, since this is the paramenter most relavant to toxicity. Differences between singly and multiply exposed groups were not significant. The three concentrations resulted in significantly different mercapturic acid percentages among the singly exposed groups. In the multiply exposed groups, the difference between the 400 ppm and the 700 ppm results was not significant, although were significantly decreased from 100 ppm results. When the exposure concentration was increased from 100 to 700 pppm, the mercapturic acid percentage of the total was reduced by 27 % for singly exposed group and 24% for the multiply exposed group.
The dose-dependent changes are postulated to be due to saturation of the metabolic elimination of chlorobenzene. The effect of multiple exposure is apparently some stimulation of metabolism.
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