Abstract  Toxline abstract: Technical rept. 19 Jun-12 Sep 90. See also Laboratory Supplement, PB92-196187. Sponsored by National Toxicology Program, Research Triangle Park, NC. 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 could be predicted 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 timed-pregnant CD and Ntilde; rats (20-25/group) on gestational days (GD) 6-15 at dose levels of 0, 800, 2,000, or 5,000 mg/kg body weight/day. Animals were observed daily for clinical signs of toxicity. Food and water weights and body weights were reported on GD 0, 3, 6, 9, 12, 15, 18, and 20. All animals were killed on GD 20 and examined for maternal body and organ weights, implant status, fetal weight, sex, and morphological development. The mid-dose (2,000 mg/kg/day DPG) produced maternal lethality in 1 out of 25 pregnant animals while the high dose (5,000 mg/kg/day) caused the death of 2 out of 22 pregnant animals. Maternal body weights were significantly decreased in the 5,000 mg/kg/day group from GD 9 through GD 20. Maternal body weight gain of the animals exposed to 5,000 mg/kg/day was significantly reduced across the treatment period and across gestation. Corrected maternal weight gain (gestation gain minus gravid uterine weight) was also significantly reduced in the 5,000 mg/kg/day group. Absolute (g/day) and relative (g/kg body weight/day) food consumption of animals in the 5,000 mg/kg/day group were significantly decreased from control for the intervals from GD 6 to 9 and GD 9 to 12. As a result, the absolute and relative food consumption was decreased during treatment (GD 6 to 15) and across gestation (GD 0 to 20). Absolute food consumption was decreased in the animals from the 2,000 mg/kg/day group from GD 6 to 9. Relative water consumption by the animals in the 5,000 mg/kg/day group was increased for all measurement periods between GD 9 and GD 18. Relative liver weight of the maternal animals was significantly increased in the animals exposed to 2,000 and 5,000 mg/kg/day of DPG. No effects of DPG were observed on pre- or post-implantation loss. The mean male and female body weights per litter were associated with a significant decreasing linear trend, but mean male and female body weights were not significantly different from control in the exposed groups. Examination of the fetuses for external, visceral and skeletal malformations and variations did not reveal any significant effects among dose groups. In summary, there was no maternal or developmental toxicity at 800 mg/kg/day of DPG. Maternal toxicity and lethality were observed at 2,000 and 5,000 mg/kg/day, but developmental toxicity was not observed even at these maternally lethal exposures.

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  Following a formulation change, a leather conditioner was involved in a 1992 nationwide outbreak of respiratory illness. We investigated the composition and toxicity of the conditioner produced before (previous product) and after (new product) the disease outbreak. The new product induced tachypnea, pulmonary edema, pulmonary hemorrhage, and sporadic deaths in exposed guinea pigs and rats. Ultrastructurally, these changes were associated with direct pulmonary cytotoxicity characterized by necrosis of alveolar type I cells and alveolar septal interstitial edema. Chemical analyses suggested major alterations in the fluorohydrocarbon constituents in the new formulation of the leather conditioner. While these alterations could not be specifically identified, they appeared to include changes from fluoralkanes to fluoroalkenes, fluorophenyl, and/or fluoroalcohol compounds. Changes in solvent composition were consistent with traces of 2-butoxyethanol and isomers of dipropylene glycol methyl ether, and additional C10–C12alkanes. In this study, we demonstrated the toxicity of the new product in laboratory animals. Some of the altered constituents of the new product have been identified and are potential candidates for additional investigations to identify specific etiologic agents.

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  In response to a request from the Deputy Administrator, Occupational Health, of the United Mine Workers of America, a study was made of possible worker exposure to two hydraulic fluids at the Old Ben Coal Company (SIC-1111) located in Benton, Illinois. Employees using Solcenic-3A hydraulic fluid or working near its area of use had reported eye, skin, or respiratory irritation. Solcenic-2 fluid produced no symptoms. Chemical analysis revealed that Solcenic-3A contained dipropylene-glycol isomers and a small amount of ethanolamine (141435) which were not present in Solcenic-2. The authors suggest that these components may lower the Solcenic-3A odor threshold. Area air evaluations indicated no harmful exposures to the component methyl-isobutyl-carbinol (108112), with exposures of 1.4 and 3.4mg/m3 determined for two of 11 samples (American Conference of Governmental Industrial Hygienists threshold limit value, 100mg/m3). No excessive exposure to the component napthenic-mineral-oil was found; it was considered that workers were exposed to it only during hydraulic line ruptures or fluid spills. Of 13 workers reporting symptoms, nine of 11 interviewed had symptoms possibly due to skin or inhalation exposure to Solcenic-3A. The authors suggest that inhalation symptoms are a reaction to its strong vapor. They conclude that there is no health hazard, but they recommend use of protective equipment, proper disposal of waste, and use of nonirritating Solcenic-2.

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  In silk‐screen printing, ink is squeezed through the open meshes of a screen carrying an image, thus transferring the image to the surface below (1, 2). Silk has been replaced by nylon, Dacron®, and polyesters (3). Previously, all the stencils were prepared manually, but now indirect photo‐mechanical processing and photo‐composition are widely used (2). Thus are printed decals, posters, wallpaper, glass, clothing, printed circuit boards, skis, surfboards, and credit cards (4).

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.