National Toxicology Program

National Toxicology Program
https://ntp.niehs.nih.gov/go/16216

IMM96015: Assessment of Contact Hypersensitivity to Dicyclohexylcarbodiimide in B6C3F1 Female Mice

The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program (NTP). The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see http://ntp.niehs.nih.gov/ntp/htdocs/levels/09-3566%20NTP-ITOX-R1.pdf). The findings and conclusions for this study should not be construed to represent the views of the NTP or the US Government.

SUMMARY

Dicyclohexylcarbodiimide (DCC) was selected for evaluation as a sensitizing agent for contact hypersensitivity in mice. DOC is most commonly used in the area of protein synthesis. It has application in the chemical and pharmaceutical industries as well as laboratory usage in the area of recombinant DNA and bioenergetics.

The objective of this study was to determine the sensitizing potential of DOC when applied dermally to female B6C3F1 mice. Measurement of the contact hypersensitivity response was accomplished by the mouse ear swelling test (MEST), and the local lymph node assay (LLNA). Concentrations to be used in the contact hypersensitivity assays were determined by irritancy studies. The doses of DOC tested were .003, .006, .03 and .06% in acetone (99.8%) for sensitization, and .1% for challenge in the MEST and .006, .03, .06 and .1% for sensitization in the LLNA. DNFB (2,4-dinitrofluorobenzene, ICN Pharmaceuticals) was used as the positive control at a concentration of .25% for sensitization, and .5% for challenge.

Dicyclohexylcarbodiimide was identified as a potential contact sensitizer in these studies. The MEST identified DCC as a sensitizer at concentrations as low as .006% at 24 (p<0.05) and 48 (p<0.01) hours post challenge. The LLNA detected a significant response with concentrations as low as .06% DOC (p<0.01). The positive control, DNFB, showed a statistically significant response in both assays

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Summary of Irritancy and Contact Hypersensitivity Results
Type of Response Method Used Dose Response (p < 0.05) Positive Response (p < 0.05)
Irritation Ear Swelling Yes Yes
.1 MIC, .06 MNC
Contact Hypersensitivity MEST 24 hrs Yes Yes
.006%

MEST 48 hrs Yes Yes
.006%

MEST Pos. Cont NA Yes

LLNA Yes Yes
.06%

LLNA Pos. Cont NA Yes

Abbreviations: Pos. cont. = positive control; LLNA = Local Lymph Node Assay; MEST = Mouse Ear Swelling Test; NA = Not Applicable; MIC= Minimal Irritating Concentration; MNC = Maximal Non-Irritating Concentration.

NTP is located at the National Institute of Environmental Health Sciences, part of the National Institutes of Health.