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Improved method for in vitro assessment of dermal toxicity for volatile organic chemicals.

Authors
Rogers-JV; McDougal-JN
Source
Toxicol Lett 2002 Sep; 135(1-2):125-135
NIOSHTIC No.
20029567
Abstract
Cell culture methods are being developed to assess the dermal toxicity (irritancy and corrosion) of chemicals. These in vitro methods are being validated to categorize chemicals as irritating or non-irritating to humans. Currently, these cell culture tests are useful to assist in the ranking of chemicals for irritancy, but they are not useful for quantitative risk assessment for two reasons. First, for volatile chemicals the amount of chemical in the media that the cells are exposed to may decrease with exposure time. Also, effective concentrations such as EC(50) and IC(50) are reported as the concentrations in the media not the skin tissue/cells. We have developed an in vitro approach for dermal toxicity testing of volatile chemicals that avoids these problems. Using sealed vials lacking a headspace, dermal equivalents (dermal fibroblasts in a collagen matrix) were exposed to culture medium containing a test chemical (m-xylene) and compared to a traditional open well culture system. We found that about 90% of the m-xylene was lost from the open well plates and the viability was 4-6 times greater than in the closed system. Partition coefficients were measured and used to estimate the m-xylene concentration in the fibroblasts. The EC(50) for m-xylene in the dermal equivalents was 833.13+/-35.33 microg m-xylene per gram of fibroblasts. This method will provide an effective approach to relate target cell chemical concentration to cellular responses. Based on this method, a biologically-based mathematical model could be used to determine an equivalent external dose for a specific toxic end point.
Keywords
Skin-irritants; Laboratory-animals; Animals; Animal-studies; Xylenes; Dermatitis; Occupational-diseases; Skin-diseases; Solvents; Exposure-levels; Exposure-assessment; In-vitro-studies
Contact
Geo-Centers, Inc., 2856 G. Street, Wright-Patterson Air Force Base, OH 45433
CODEN
TOLED5
CAS No.
1330-20-7; 151-21-3; 138-86-3
Publication Date
20020905
Document Type
Journal Article
Funding Type
Grant
Fiscal Year
2002
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-000354
Issue of Publication
1-2
ISSN
0378-4274
Source Name
Toxicology Letters
State
OH
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