National Toxicology Program

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NTP Report on the Assessment of Contact Hypersensitivity to 2-Ethyl-2-(Hydroxymethyl)-1,3-Propanediol Triacrylate (Trimethylolpropane Triacrylate) in Female B6C3F1 Mice (CASRN: 15625-89-5)

ABSTRACT

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 The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by the NTP on March 2009 (see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.

NTP Report Number IMM95008

Summary

Introduction: Acrylate esters have a widespread use in the manufacturing of numerous industrial and consumer products. They are most commonly used to produce polymers and resins used in such products as latex paint, fabric finishes, floor polishes, specialty plastics and dirt release agents [international Agency for Research on Cancer (IARC), IARC Monogr. Eval. Carcinog. Risk Chem. Man 19, 57-62, 1979]. Occupational exposure to these compounds occurs primarily by inhalation or skin exposure. 2-Ethyl-2-(Hydroxymethyl)-1,3-Propanediol Triacrylate (2-ETAC) was selected for evaluation as a sensitizing agent for contact hypersensitivity in mice.

Design: 2-ETAC was obtained from Aldrich Chemical Company as a clear liquid. Dilutions were made in acetone which served as the vehicle. Three assays were used in this assessment, a primary irritancy study, to screen for toxicity and determine the Minimal Irritating Concentration (MIC) and the Maximal Non- Irritating Concentration (MNC) and two assays, the Mouse Ear Swelling Test (MEST) and the Local Lymph Node Assay (LLNA), to test the dermal sensitizing potential of 2-ETAC.

For irritancy testing, in two separate studies, nine mice each were used to test four concentrations of test article in vehicle plus vehicle and untreated controls. Each mouse received a different treatment on each of its ears, one on the right ear and one on the left ear. The treatment combinations may be two different concentrations of test material, one concentration of test material and the vehicle, one concentration of the test material and no treatment, or the vehicle and no treatment. Each concentration of test material and the vehicle were tested three times. Animals were dosed on 4 consecutive days and checked daily for signs of morbidity. The lowest concentration of test article demonstrating significant irritation, as determined by the percent ear swelling at 24 hrs post last treatment, was considered the MIC. The highest concentration not to demonstrate a significant irritation over the vehicle controls was considered the MNC. Doses chosen for the hypersensitivity assays were based on the MIC and MNC. The design for the MEST is shown in the table below (Table 1). Pre, 24 and 48 hr post treatment ear measurements were taken and used to calculate th e percent ear swelling. Measurements from animals dosed with varying concentrations of test article were compared to the 2-ETAC background control for significance. When a no effect level was not determined in the first study a second study was run using decreasing concentrations of 2-ETAC. The chemical concentrations and experimental groups used for the LLNA are shown in the table below (Table 2). After 3 consecutive days of dosing, animals were rested for 1 day and then injected with 3H-thymidine, lymph nodes dissected out 5 hours later and radioassayed. Chemical exposed groups were compared to vehicle controls for statistical significance. When a no effect level was not determined in the first study a second study was run using decreasing concentrations of 2-ETAC.

Table 1

Group Exp. Group No. of Mice Sensitization Challenge
1 VH 8 Vehicle Vehicle
2 BC 8 Vehicle MIC
3 D3 8 MNC MIC
4 D2 8 0.3 MNC MIC
5 D1 8 0.1 MNC MIC
6 BP 8 Vehicle 0.5% DNFB
7 PC 8 0.25% DNFB 0.5% DNFB
Abbreviations: VH=vehicle; BC=background control; MNC=maximal non-irritating concentration; MIC=mInimal irritating concentration: BP=background positive; PC=positive control; DNFB=2,4-Dinitrofluorobenzene

Table 2

Exp. Group No. of Mice Induction
VH 5 Vehicle
D3 5 MIC
D2 5 MNC
D1 5 0.5 MNC
PC 5 0.25% DNFB
Abbreviations: VH=vehicle; MIC=minimal irritating concentration; MNC=maximal non-irritating concentration; PC=positive control; DNFB=2,4-Dinitrofluorobenzene

Results: There were no treatment-related effects on survival or body weights. Irritancy studies testing 2-ETAC determined the Minimal Irritating Concentration to be 1.0% and the Maximal Non-irritating Concentration to be 0.3%. A statistically significant allergic contact hypersensitivity response was demonstrated by the MEST in mice sensitized with concentrations as low as 0.03% 2-ETAC. The positive control group produced a statistically significant contact hypersensitivity response at a sensitizing concentration of 0.25% and challenge concentration of 0.5% DNFB as compared to the 0.5% DNFB challenge only group. In the LLNA, concentrations as low as 0.1% 2-ETAC (Figure 2) and 0.25% DNFB (the positive control) caused a significant response as compared to the vehicle treated group.

Conclusions: 2-Ethyl-2-(Hydroxymethyl)-1,3-Propanediol Triacrylate was identified as a potential contact sensitizer in these studies. 2-ETAC showed irritating activity at concentrations as low as 1%. It elicited a hypersensitivity response as measured by the MEST at concentrations as low as 0.03% and as low as 0.1% as measured by the LLNA. No effect levels as measured by the MEST and LLNA were.01 and.03% respectively. In these studies the MEST was found to be a more sensitive indicator of the sensitizing potential of 2-ETAC.

Report Date: January 1995

 


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