Abstract  In a prior study on electronic cigarette (EC) refill fluids, Cinnamon Ceylon was the most cytotoxic of 36 products tested. The purpose of the current study was to determine if high cytotoxicity is a general feature of cinnamon-flavored EC refill fluids and to identify the toxicant(s) in Cinnamon Ceylon. Eight cinnamon-flavored refill fluids, which were screened using the MTT assay, varied in their cytotoxicity with most being cytotoxic. Human embryonic stem cells were generally more sensitive than human adult pulmonary fibroblasts. Most products were highly volatile and produced vapors that impaired survival of cells in adjacent wells. Cinnamaldehyde (CAD), 2-methoxycinnamaldehyde (2MOCA), dipropylene glycol, and vanillin were identified in the cinnamon-flavored refill fluids using gas chromatography–mass spectrometry and high-pressure liquid chromatography (HPLC). When authentic standards of each chemical were tested using the MTT assay, only CAD and 2MOCA were highly cytotoxic. The amount of each chemical in the refill fluids was quantified using HPLC, and cytotoxicity correlated with the amount of CAD/product. Duplicate bottles of the same product were similar, but varied in their concentrations of 2MOCA. These data show that the cinnamon flavorings in refill fluids are linked to cytotoxicity, which could adversely affect EC users.

Abstract  The dermal penetration of undiluted monopropylene glycol (MPG) and dipropylene glycol (DPG) has been measured in vitro using human abdominal skin under conditions of infinite dose application, and the results compared with predictions from the SKINPERM QSAR model (ten Berge, 2009). The measured steady-state penetration rates (J(ss)) for MPG and DPG were 97.6 and 39.3 mu g/cm(2)/h, respectively, and the permeability coefficients (K(p)) were 9.48 x 10(-5) cm/h for MPG and 3.85 x 10(-5) cm/h for DPG. In comparison, the SKINPERM model slightly over-predicted J(ss) and K(p) for MPG and DPG by between 2.6- and 5.1-fold, respectively. The model predictions of 254 mu g/cm(2)/h and 24.6 x 10(-5) cm/h for MPG, and 202 mu g/cm(2)/h and 19.8 x 10(-5) cm/h for DPG were in fairly good agreement with the measured values. Further, the model predicted a J(ss) of 101 mu g/cm(2)/h and a Kp of 9.9 x 10(-5) cm/h for the homologue tripropylene glycol. Assuming that the measured J(ss) was the same under conditions of finite dose application (taken to be 10 mu L/cm(2)) and was maintained over a 24-h period (both conservative assumptions), the relative dermal absorption of the applied dose was estimated to be 23% (0.96%/h) for MPG and 9% (0.39%/h) for DPG. However, the extrapolation for MPG may be further overestimated due to possible residence in the stratum corneum under infinite conditions of exposure that would not be applicable to a finite loading dose. (C) 2011 Elsevier Ltd. All rights reserved.

Abstract  Toxline abstract: Topics: animal experiments; 1,4-diethylbenzene; 1,4-dibromobenzene; dibutyl phosphate; m-toluidine; n-butyl chloride; 3-aminobenzenesulfonic acid; C.I. Pigment Green 7; tripropylene glycol; 3-methyl-4-nitrophenol; cresyl diphenyl phosphate; tris(p-cumenyl)phosphate; methoxymethanol; 2,3-dibromosuccinic acid; D and C Red No.7; diethyl fumarate; 2,2,4-trimethyl-1,3-pentanediol diisobutyrate; triisobutylene; tris(2-ethylhexyl) phosphate; 1-naphthylacetic acid; 4-(1-methylpropyl)phenol; Japan; toxic effects; toxic substances; toxicity evaluation; toxicology.

Abstract  In a pollution prevention and chemical substitution effort, the U.S. Air Force and Navy formed a joint initiative to find safer, more environmentally acceptable jet fuel system icing inhibitors (FSII) for military aircraft. Standard biochemical oxygen demand (BOD) analysis and variations of the BOD procedure were used as simple screening tools to evaluate the potential for aquatic biodegradation and microbial toxicity of proposed FSIIs. This laboratory evaluation of biological properties allows prediction of the biotreatability of the chemicals in wastewater treatment plants, and their potential application as biocides at higher concentrations. The current FSII, diethylene glycol monomethyl ether (DiEGME) was evaluated along with two new candidate compounds, dipropylene glycol and glycerol formal. At a low concentration (3.5 mg/L), DiEGME exerted a BOD5 of about 27% of theoretical oxygen demand. Test concentrations of ≥7 mg/L had decreasing oxygen consumption rate and extent, typical of a material with potential aquatic microbial toxicity. Dipropylene glycol began to moderately degrade only after more than 3 weeks exposure to microorganisms obtained from raw sewage. Glycerol formal showed no signs of biodegradation during a 5‐week test period. In a simple microbial toxicity test DiEGME was most toxic, dipropylene glycol was moderately toxic, and glycerol formal showed little toxicity. At low concentrations (7 mg/L), none of the chemicals significantly inhibited microbial activity (P=0.34).

Abstract  Dipropylene glycol (DPG) is a high production glycol used in the manufacture of nitrocellulose solvent, lacquers, paints, printing inks, and shellac varnishes: In general, the toxicity of the glycols decreases as the molecular weight of the molecule increases. Therefore, it was expected that DPG would be less toxic than low molecular weight glycols such as ethylene glycol. Since, there is a lack of data with which to confirm this hypothesis this study was conducted to assess the potential for DPG to cause developmental toxicity and to compare its toxicity to other glycols. DPG (CAS No. 25265-71-8) was administered by gavage to artificially inseminated NZW rabbits (24/group) on gestation days (GD) 6-19 at dose levels of 0, 200, 400, 800, or 1200 mg/kg body weight/day. Animals were observed daily for clinical signs of toxicity. Mean food and body weights were calculated for each group on GD 0, 6, 9, 12, 15, 19, 25, and 30. All animals were killed on GD 30 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development. No maternal lethality occurred in this study. Pregnancy rates were 95%, 83%, 91%, 92%, and 82% in the control to high dose groups, respectively. No effect that could be attributed to exposure to DPG was noted on maternal body weight, food consumption, or clinical signs. Necropsy of the maternal animals revealed no effects on kidney and liver weights. In utero DPG exposure did not affect the frequency of post-implantation loss, mean fetal body weight per litter, or external, visceral, or skeletal malformations. In summary, no maternal toxicity was observed in animals exposed to 1200 mg/kg/day of DPG from GD 6 through GD 19 although preliminary study data (NTP, 1990a) indicated this exposure to be in the maternally toxic range for this species. No developmental toxicity was noted in the offspring of the animals from any group exposed to DPG during this study. The study established a NOAEL of at least 1200 mg/kg/day for both maternal and developmental toxicity of dipropylene glycol administered orally in rabbits.

Abstract  The effects of various cosmetic ingredients, including preservatives, humectants, ultraviolet absorbents and solvents, on the electrical properties of neuronal cells were investigated using rat phaeochromocytoma PC12 cells and cultured rat dorsal root ganglion (DRG) neurons. When membrane current was measured under whole-cell voltage-clamp, all nine test compounds inhibited voltage-activated K super(+) current in PC12 cells. With the five compounds selected for further experiments with DRG neurons, two types of current responses were observed, namely inhibition of K super(+) current by methyl or butyl p-hydroxybenzoate (MPHB or BPHB) and resorcinol, and induction of a cationic inward current by MPHB, BPHB, ethanol and dipropylene glycol. The order of potency of these chemicals to inhibit the K super(+) current in PC12 cells was similar to that of their cytotoxicity, which was determined by MTT assay. Capsaicin, BPHB, MPHB and resorcinol, however, inhibited the K super(+) current at concentrations lower than those required for cytotoxicity. These results suggest that these cosmetic ingredients exert significant effects on the electrical properties of cultured neuronal cells. This electrophysiological method may be useful in prescreening test systems to detect stinging, and also to clarify mechanisms underlying the irritation induced by a variety of compounds.

Abstract  BACKGROUNDDipropylene glycol is found in antifreeze, air fresheners, cosmetic products, solvents, and plastics. We studied the effects of dipropylene glycol on male and female rats and mice to identify potential or cancer-related hazards to humans.METHODSWe gave groups of 50 male and female mice drinking water containing dipropylene glycol at concentrations of 10,000, 20,000, or 40,000 parts per million (corresponding to 1%, 2%, or 4%) for two years. Male and female rats received concentrations of 2,500, 10,000, or 40,000 parts per million. Other groups received untreated water and were the control group. Tissues from more than 40 sites were examined for every animal.RESULTSThe groups of animals receiving 40,000 ppm dipropylene glycol weighed less than the control animals. All the make rats receiving 40,000 ppm dipropylene glycol died before the end of the study, mainly because of kidney disease. All the other animal group survived as well as the controls. No increase in tumor rates were seen in any of the groups of rats or mice.CONCLUSIONSWe conclude that dipropylene glycol did not cause cancer in male or female rats or mice. Exposure to dipropylene glycol did increase the rate and severity of kidney nephropathy and inflammation of the liver and salivary gland in male rats and some atrophy of the epithelial tissue of the nose in male and female rats.