PMID- 11397425
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20190826
IS  - 0009-2797 (Print)
IS  - 0009-2797 (Linking)
VI  - 135-136
DP  - 2001 Jun 1
TI  - In vitro genotoxicity testing of (1-chloroethenyl)oxirane, a metabolite of 
      beta-chloroprene.
PG  - 703-13
AB  - (1-Chloroethenyl)oxirane (CEO) is a metabolite of beta-chloroprene 
      (2-chloro-1,3-butadiene, CD). The purpose of this study was to evaluate the in 
      vitro mutagenic and clastogenic (chromosome breaking) potential of CEO. For 
      comparative purposes, the study also included an evaluation of the racemic 
      compounds, 3,4-epoxy-1-butene (EB) and 1,2:3,4-diepoxybutane (DEB). Mutagenicity 
      was evaluated in a bacterial reverse mutation test (Ames), using the 
      pre-incubation method in the presence and absence of an exogenous metabolism 
      system (Aroclor)-induced rat liver S9). Four Salmonella typhimurium tester 
      strains, TA97a, TA98, TA100 and TA1535 were used. The exposure concentrations in 
      the sealed incubation vials ranged from 0 to 69 mM for CEO, 0 to 102 mM for EB, 
      and 0 to 83 mM for DEB. All three compounds showed signs of toxicity, with DEB 
      being substantially more toxic than either CEO or EB. Mutagenic activity was 
      observed with all three chemicals in primarily the base pair substitution strains 
      (S. typhimurium TA100 and TA1535), but some activity was also seen in the 
      frameshift elimination strains (S. typhimurium TA97a and TA98). The observed 
      mutagenic responses after exposure with CEO or EB were greater than the observed 
      response for DEB, most likely because of the higher toxicity of DEB. Generally, 
      the mutagenic responses were unchanged in the frameshift strains and base pair 
      substitution strains in the presence of S9 metabolism. In vitro clastogenicity 
      was evaluated using the cytochalasin-B blocked micronucleus test in cultured 
      Chinese hamster V79 cells. The test was conducted without S9 metabolism because 
      of the absence of substantial changes in the Ames test. Exposure concentrations 
      ranged from 0 to 0.943 mM for CEO, 0 to 3.0 mM for EB, and 0 to 0.035 mM for DEB, 
      with the upper exposure concentrations dictated by cytotoxicity. Cytotoxicity, 
      measured as a reduction in the proportion of binucleated cells and altered cell 
      morphology, was observed for CEO at concentrations > or =0.175 mM. Exposure to EB 
      led to a reduced proportion of binucleated cells at concentrations > or =2.0 mM, 
      and cell death was observed after DEB exposure at concentrations > or =0.025 mM. 
      No clastogenicity was observed in the V79 cells when tested up to cytotoxic 
      concentrations of CEO, whereas an elevated frequency of micronuclei was observed 
      after exposure to either EB (> or =1.0 mM) or DEB (> or =0.0125 mM). These 
      results suggest that CEO-induced mutagenicity, but not clastogenicity, may 
      contribute to the observed beta-chloroprene-induced carcinogenicity in the rodent 
      bioassay studies.
FAU - Himmelstein, M W
AU  - Himmelstein MW
AD  - E.I. du Pont de Nemours and Company, Haskell Laboratory for Toxicology and 
      Industrial Medicine, PO Box 50, 1090 Elkton Road, Newark, DE 19711, USA. 
      matthew.w.himmelstein@usa.dupont.com
FAU - Gladnick, N L
AU  - Gladnick NL
FAU - Donner, E M
AU  - Donner EM
FAU - Snyder, R D
AU  - Snyder RD
FAU - Valentine, R
AU  - Valentine R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Chem Biol Interact
JT  - Chemico-biological interactions
JID - 0227276
RN  - 0 ((1-chloroethenyl)oxirane)
RN  - 0 (Epoxy Compounds)
RN  - 0 (Mutagens)
RN  - 126-99-8 (Chloroprene)
RN  - 478ERR5NKR (3,4-epoxy-1-butene)
RN  - 60OB65YNAB (diepoxybutane)
RN  - JJH7GNN18P (Ethylene Oxide)
SB  - IM
MH  - Animals
MH  - Chloroprene/*metabolism/*toxicity
MH  - Epoxy Compounds/metabolism/toxicity
MH  - Ethylene Oxide/analogs & derivatives/*metabolism/*toxicity
MH  - Frameshift Mutation
MH  - In Vitro Techniques
MH  - Liver/metabolism
MH  - Mutagenicity Tests
MH  - Mutagens/*metabolism/*toxicity
MH  - Point Mutation
MH  - Rats
MH  - Salmonella typhimurium/drug effects/genetics
EDAT- 2001/06/09 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/06/09 10:00
PHST- 2001/06/09 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/06/09 10:00 [entrez]
AID - S0009279701002034 [pii]
AID - 10.1016/s0009-2797(01)00203-4 [doi]
PST - ppublish
SO  - Chem Biol Interact. 2001 Jun 1;135-136:703-13. doi: 
      10.1016/s0009-2797(01)00203-4.