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Toxicological information

Specific investigations: other studies

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Administrative data

Endpoint:
hematoxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-guideline experimental study with clearly reported methods and results, no indication as to GLP status. Adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Comparative toxicity of known and putative metabolites of 1,3-butadiene in human CD34+ bone marrow cells.
Author:
Irons RD, Pyatt DW, Stillman WS, Som DB, Claffey DJ, Ruth JA.
Year:
2000
Bibliographic source:
Toxicology, 150:99–106.

Materials and methods

Principles of method if other than guideline:
This study evaluated the effect of several BD metabolites on colony formation and cytotoxicity in human CD34+ haematopoietic progenitor cells. The metabolites tested were: 3,4-epoxybutene (EB); two enantiomers of diepoxybutane (BDE), d,l-butane-bis-oxide and meso-butane-bis-oxide; and (2S,3R)-3-epoxybutane-1,2-diol (BDO).
GLP compliance:
not specified
Type of method:
in vitro

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
the test materials are metabolites of 1,3-butadiene found both in vivo and in vitro

Test animals

Species:
human

Results and discussion

Applicant's summary and conclusion

Executive summary:

This study evaluated the effect of several BD metabolites on colony formation and cytotoxicity in human CD34+ haematopoietic progenitor cells. The metabolites tested were: 3,4-epoxybutene (EB); two enantiomers of diepoxybutane (BDE), d,l-butane-bis-oxide and meso-butane-bis-oxide; and (2S,3R)-3-epoxybutane-1,2-diol (BDO). Procedures involving volunteers were reviewed and approved by the institutional internal review board, and volunteers were recruited by informed consent.

Human CD34+ cells (>95% purity) were isolated from bone marrow obtained from volunteers and exposed to test substances (10-8–10-4M) and cytokines (granulocyte-macrophage/colony-stimulating factor, GM-CSF; erythropoietin, EPO; interleukin-3, IL-3; stem cell factor, SCF) for 16h at 37°C. Colonies were scored after 14 days as multi-lineage myeloid, i.e. granulocyte erythroid-megakaryocyte-macrophage (GEMM), granulocyte-macrophage (CFU-GM) or erythroid burst forming units (BFU-E).

The two BDE enantiomers caused a concentration-dependent suppression of clonogenic response, but EB and BDO were without effect. It is concluded that, in contrast to murine haematopoietic progenitor cells, human cells are insensitive to EB, and are only sensitive to BDE.