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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see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.
The Immunotoxicity of Ethylene Thiourea
(CAS No. 96-45-7)
Contact Hypersensitivity Studies in Female B6C3F1 Mice
NTP Report Number: IMM90009
Ethylene thiourea (ETU) is used in electroplating baths, as a chemical intermediate in the manufacture of pesticides, dyes, and pharmaceuticals, and as a curing agent in several chemical processes. In humans it can produce skin and eye irritation as well as myxedema with thickening and drying of the skin. A study has described an allergic contact dermatitis response to ETU in one individual (Bruze and Fregert, Contact Dermatitis 9:208, 1983). The studies to be described were designed to determine its sensitizing potential when applied to mouse skin.
ETU was obtained from the Aldrich Chemical Corporation Corp., Milwaukee, WI, (Lot #PC081687/B01) and was greater than 99% pure, as determined by HPLC. The material was prepared in ethylene glycol, which also served as the vehicle. Primary irritancy studies indicated that all concentrations of ETU tested (up to 30%) were non-irritating when applied to the prepared dorsal surface of female B6C3F1 mice although concentrations greater than 10% were not soluble in the vehicle. A 0.5% solution of 1-fluoro- 2,4-dinitrobenzene (DNFB; Sigma Chemical Corp.; Lot No. 88F-3833; > 99% pure as determined by HPLC) was used as a positive control. For the hypersensitivity test, groups of female B6C3F1 mice were sensitized to ETU by application of 1.0%, 3.0%, or 10.0% ETU for 5 consecutive days to a prepared dorsal surface site. Seven days after the last application, mice were challenged with a 10% concentration of ETU on the dorsal and ventral sides of the left ear. Site preparation included intradermal injection of Freund's complete adjuvant in some mice. Mice were divided into 10 treatment groups of 8 mice per group as shown in Table 1. The irritancy response was determined by monitoring the extravasation of 125I- bovine serum albumin into the treated area. The contact hypersensitivity response was determined by monitoring the infiltration of 125I-iododeoxyuridine labeled cells into the challenge site in addition to the mouse ear swelling test.
There were no treatment-related effects on survival or body weights. There was no evidence of skin irritation in the form of erythema or edema in any of the treatment groups. No statistically significant or dose-related hypersensitivity response was observed in mice sensitized with 1%, 3%, or 10% ETU and challenged with 10% ETU by either the radioisotopic method (data not shown) or the mouse ear swelling test (Figure 1). The positive response with 0.5% DNFB is shown for comparison (Group 6).
Under these experimental conditions, no statistically significant or dose-dependent contact hypersensitivity responses to ETU were observed in mice following dermal exposure.
Table 1. Study Design: Contact Hypersensitivity Study with Ethylene Thiourea
|2 (8)||Baseline Control||+||Vehicle||10% ETU|
|3 (8)||Experimental||+||1% ETU||10% ETU|
|4 (8)||Experimental||+||3% ETU||10% ETU|
|5 (8)||Experimental||+||10% ETU||10% ETU|
|6 (8)||DNFB Positive Control||-||0.5% DNFB||0.5% DNFB|
|7 (8)||DNFB Negative Control||-||Vehicle||0.5% DNFB|
|8 (8)||Baseline Control||-||Vehicle||10% ETU|
|9 (8)||Experimental||-||3% ETU||10% ETU|
|10 (8)||Experimental||-||10% ETU||10% ETU|
note: ETU = ethylene thiourea; FCA = Freund's complete adjuvant; DNFB = 1-fluoro-2,4-dinitrobenzene