tripropylene-glycol-diacrylate and ethyl-acrylate

The potential for occupational exposure to the esters of acrylic acid (acrylates) is considerable, and, thus, requires a greater understanding of the their toxicity. Confluent (70-90%) cultures of normal human epidermal keratinocytes (NHEK), dermal fibroblasts (NHDF). or bronchial epithelium (NHBE) were exposed to the monofunctional ethyl acrylate (EA), the multifunctional tripropylene glycol diacrylate (TPGDA), or TPGDA monomer in a radiation curable lacquer (Lacquer A) at equimolar dosages in order to determine human in vitro cytotoxicity. Viability of the cells after 2-24-h exposure to the representative monofunctional or multifunctional acrylate or solvent control was used to calculate an index of acute cytotoxicity (50% inhibitory dose; ID50) and to determine the shape of the dose-response curves. TPGDA, Lacquer A, and EA were equally cytotoxic (ID50 is approximately equal to 0.1 micromol/cm2) to NHEK at equimolar doses. TPGDA or Lacquer A were more cytotoxic (is approximately equal to 100X) to NHDF or NHBE than EA. Sequential exposure of UV(A) and TPGDA to NHEK indicate the potential for a synergistic cytotoxic response. These findings are consistent with observed decreases in free sulfhydryl groups (e.g., glutathione or cysteine) that parallel the dose-response-related decreases in viability. logether, these data suggest possible differences in toxicity between the monofunctional EA and multifunctional TPGDA to NHEK, NHDF. or NHBE, possibly due to the difference in the number of functional acrylate groups and/or physicochemical differences (e.g., vapor pressure) between the acrylates investigated.

Topics: Acrylates; Carcinogens; Epithelial Cells; Fibroblasts; Humans; Keratinocytes; Lung; Propylene Glycols; Skin

Acrylates may be polymerized to stable surface coatings (paints, lacquers, inks, etc.) by alkylation via the Michaelis-type addition reaction. Thus, acrylates have an inherent potential as electrophiles to be genotoxic, limited in their biological activity by their physicochemical properties. To evaluate their systemic genotoxicity, ethyl acrylate (EA), tripropylene glycol diacrylate (TPGDA), or Lacquer A, an ultraviolet radiation curable lacquer containing TPGDA as the active ingredient, were applied dermally to Tg.AC mice (3 times a week for 20 weeks). Peripheral blood leukocytes were evaluated for DNA damage (single-strand breaks, alkali labile sites, DNA crosslinking) at weeks 4, 8, 12, 16, and 20 by using the alkaline (pH: 13) single cell gel (SCG) assay. Peripheral blood polychromatic erythrocytes (PCE) and normochromatic erythrocytes (NCE) were evaluated for the presence of micronuclei at week 20. The extent of DNA migration in leukocytes and the frequency of micronucleated erythrocytes was not significantly altered by treatment with TPGDA when administered alone or in Lacquer A or with EA, at doses that induced cell proliferation in keratinocytes. The absence of genotoxicity in these two cell populations suggests that these acrylates are not genotoxic or that they are not absorbed systemically when applied dermally. However, a significant, dose-dependent increase in the percentage of PCE relative to the vehicle control was present in mice treated with TPGDA, while a dose-dependent, but nonsignificant, increase in the percentage of PCE was observed in mice treated with Lacquer A. This observed increase in the rate of erythropoiesis may reflect bone marrow/blood toxicity, a homeostatic mechanism in response to the treatment-induced tumor burden, and/or a hematopoietic response to epidermal keratinocyte cytokines induced by tissue injury.

Topics: Acrylates; Administration, Topical; Animals; DNA Damage; Erythrocytes, Abnormal; Female; Mice; Mice, Transgenic; Micronucleus Tests; Propylene Glycols