Disease relevance of CCRIS 2458

• Toxicity of chloroprene, 1,3-dichlorobutene-2, and 1,4-dichlorobutene-2 [1].

High impact information on CCRIS 2458

• Participants in the highest decile of 1,4-DCB concentration had decrements of -153 mL [95% confidence interval (CI) , -297 to -8] in forced expiratory volume in 1 sec and -346 mL/sec (95% CI, -667 to -24) in maximum mid-expiratory flow rate, compared with participants in the lowest decile [2].
• In addition, CHO/HPRT-gene mutation tests with 1,4-DCB and 2,5-DCP yielded negative results for both compounds with and without metabolic activation system [3].
• The genotoxic potential of 1,4-dichlorobenzene (1,4-DCB) has been extensively evaluated in vitro and in vivo [3].
• Phenobarbital pretreatment of rats enhanced the in vitro conversion of 1,4-DCB and the amount of covalent binding [4].
• Nephrotoxicity and biochemical alterations induced by 1,4-DCB resemble those of unleaded gasoline and suggest that a similar mechanism is involved in the induction of alpha 2u-globulin nephropathy in male rats [5].

Biological context of CCRIS 2458

• 1,3-DCB is a by-product of beta-chloroprene from the acetylene route, with 1,4-DCB is an intermediate in the production of beta-chloroprene from the butadiene route, the production route used in the U.S. Presented in the review is a summary of the acute toxicity including mutagen testing, skin, eye, and inhalation testing of these compounds [1].
• The observed species differences, notably the more pronounced biotransformation of 1,4-DCB to reactive species including benzoquinones, could be factors in this compound's liver carcinogenicity in B6C3F1 mice but not other rodent species [4].
• Renal cell proliferation, measured by [3H]thymidine incorporation into renal DNA, was increased after 1,4-DCB but not after 1,2-DCB treatment [5].
• Significant species and sex differences in the oxidation of MCB, 1,2-DCB and 1,4-DCB were reflected in a markedly higher oxidation in male mice than male rats and higher oxidation in male than female mice [6].

Anatomical context of CCRIS 2458

• Following long-term inhalation (450 and 3000 mg/m3) 1,4-DCB concentrations were highest in adipose tissues at 6 months followed by a marked decline at 18 months [7].
• Metabolic rates of MCB, 1,2-DCB and 1,4-DCB correlated with CYP2E1 immunochemical level in microsomes from 11 different human livers and with metabolic rates of CYP2E1 substrates [6].

Associations of CCRIS 2458 with other chemical compounds

• Nasal tumors in rats following long-term inhalation exposure to 1,4-dichlorobutene-2 (DCB) [8].

Gene context of CCRIS 2458

• The relative roles of human liver CYP2E1 and 3A4 in the metabolism of 1,4-DCB seem to be individually different [6].
• In contrast to previous studies showing rat CYP3A1 as the main CYP form oxidising both DCBs, our experiments indicate only a certain role of rat and human CYP3A in MCB, 1,2-DCB and 1,4-DCB oxidation to covalently bound products [6].
• The toxicity produced by 1,4-DCB was suppressed by amino acids, vitamins and 1% BSA [9].

Analytical, diagnostic and therapeutic context of CCRIS 2458

• Gel filtration chromatography of a 116,000g supernatant prepared from kidneys of 1,4-[14C]DCB-treated rats showed that radiolabel coeluted with alpha 2u-globulin as one sharp peak as opposed to a multipeak pattern observed for 1,2-[14C]DCB; the maximal quantity of radiolabel for 1,4-DCB was twice that for 1,2-DCB [5].
• 1,4-Dichlorobenzene (1,4-DCB) was shown to induce the formation of male rat renal tubule tumors and male and female mouse liver tumors when administered in a chronic bioassay [10].
• After single oral administration of 100 and 1000 mg/kg bw and feeding of 100 and 1000 ppm (corresponding to approximately 10 and 100 mg/kg bw) to male Wistar rats for 28 days, the time course of 1,4-DCB and 2,5-DCP concentrations was investigated in plasma, adipose, hepatic and renal tissue [7].

References