Assessment of the potential risk of 1,2-hexanediol using phytotoxicity and cytotoxicity testing.

1,2-Hexanediol is commonly used in the cosmetic industry as a preservative, an emollient, and a moisturizing agent. However, studies on the scientific toxicity of 1,2-hexanediol are limited. In this study, we evaluated the potential toxic effects of 1,2-hexanediol using phytotoxicity and cytotoxicity testing methods. Phytotoxicity tests using Brassica campestris subsp. napus and Latuca sativa L. showed that 1,2-hexanediol significantly inhibited seed germination and root elongation at the lowest concentration (0.1%). Additionally, plants treated with 1,2-hexanediol failed to survive. In cytotoxicity tests, RAW 264.7 and HK-2 cells treated with 1.0% 1,2-Hexanediol showed a significant decline in viability, followed by death. Since most personal care products contain >2% 1,2-hexanediol, it is highly likely that 1,2-hexanediol is toxic to humans. Moreover, if 1,2-hexanediol enters the human body either via oral intake or through an open wound, it could have critical effects. Furthermore, upon release into the environment, 1,2-hexanediol could cause considerable damage to plants and other organisms. Therefore, further investigation of 1,2-hexanediol is required to prevent toxicity to humans and other living organisms.

Multi-dimensional in vitro bioactivity profiling for grouping of glycol ethers.

High-content screening data derived from physiologically-relevant in vitro models promise to improve confidence in data-integrative groupings for read-across in human health safety assessments. The biological data-based read-across concept is especially applicable to bioactive chemicals with defined mechanisms of toxicity; however, the challenge of data-derived groupings for chemicals that are associated with little or no bioactivity has not been explored. In this study, we apply a suite of organotypic and population-based in vitro models for comprehensive bioactivity profiling of twenty E-Series and P-Series glycol ethers, solvents with a broad variation in toxicity ranging from relatively non-toxic to reproductive and hematopoetic system toxicants. Both E-Series and P-Series glycol ethers elicited cytotoxicity only at high concentrations (mM range) in induced pluripotent stem cell-derived hepatocytes and cardiomyocytes. Population-variability assessment comprised a study of cytotoxicity in 94 human lymphoblast cell lines from 9 populations and revealed differences in inter-individual variability across glycol ethers, but did not indicate population-specific effects. Data derived from various phenotypic and transcriptomic assays revealed consistent bioactivity trends between both cardiomyocytes and hepatocytes, indicating a more universal, rather than cell-type specific mode-of-action for the tested glycol ethers in vitro. In vitro bioactivity-based similarity assessment using Toxicological Priority Index (ToxPi) showed that glycol ethers group according to their alcohol chain length, longer chains were associated with increased bioactivity. While overall in vitro bioactivity profiles did not correlate with in vivo toxicity data on glycol ethers, in vitro bioactivity of E-series glycol ethers were indicative of and correlated with in vivo irritation scores.

Prenatal exposure to glycol ethers and sex steroid hormones at birth.

BACKGROUND: Glycol ethers (GEs) are oxygenated solvents widely found in occupational and consumer water-based products. Some of them are well-known reproductive and developmental toxicants. OBJECTIVES: To study the variations in circulating sex steroid hormones, measured in cord blood, according to biomarkers of prenatal GE exposure. METHODS: The study population comes from the PELAGIE mother-child cohort, which enrolled pregnant women from Brittany (France, 2002-2006). Maternal urine samples were collected from a random subcohort (n = 338) before 19 weeks' gestation, from which we measured 8 alkoxycarboxylic metabolites of GEs. We subsequently measured 13 sex steroid hormones and sex hormone-binding globulin (SHBG) in cord blood samples. Linear regressions adjusted for potential confounders were used, and nonlinear dose-response associations were investigated. RESULTS: The detection rates of GE metabolites ranged from 4% to 98%; only the 5 most detected (>20%) metabolites were investigated further. Phenoxyacetic acid (detection rate > 95%) was associated with lower levels of SHBG and various steroids (17-alpha-hydroxy-Pregnenolone, delta-5-androstenediol, and dehydroepiandrosterone) among boys and higher SHBG and 16-alpha-hydroxy-dehydroepiandrosterone levels among girls. The two other highly detected metabolites, methoxyetoxyacetic acid and butoxyacetic acid, were associated with variations in estradiol. Butoxyacetic acid was associated with higher delta-5-androstenediol levels while detectable levels of methoxyacetic acid were associated with lower levels of this hormone. CONCLUSION: Our study suggests that prenatal exposure to GE may affect endocrine response patterns, estimated by determining blood levels of sex steroid hormones in newborns. These results raise questions about the potential role of these changes in the pathways between prenatal GE exposure and previously reported adverse developmental outcomes, including impaired neurocognitive performance.

Inhibition of germinal vesicle breakdown in Xenopus oocytes in vitro by a series of substituted glycol ethers.

A 24 hour in vitro Xenopus oocyte maturation (germinal vesicle breakdown [GVBD]) assay developed by Pickford and Morris (Environmental Health Perspectives, 1999, 107, 285-292) was used to screen a series of substituted glycol ethers (GEs). Substituted GEs included: ethylene glycol monomethyl ether (EGME); EG monoethyl ether (EGEE); EG monopropyl ether (EGPE); EG monobutyl ether (EGBE); EG monohexyl ether (EGHE); diethylene glycol monomethyl ether (DGME); triethylene glycol monomethyl ether (TGME); ethylene glycol monophenyl ether (EGPhE); EG monobenzyl ether (EGBeE); EG diphenyl ether (EGDPhE); and propylene glycol monophenyl ether (PGPhE). The GEs inhibited progesterone- or androstenedione-induced GVBD with the following relative potency: EGPhE > PGPhE > EGME >> EGEE ≥ EGBeE > EGPE >> EGBE >EGHE > EGDPhE >> DGME ≥ TGME, or EGPhE >> PGPhE >> EGBeE > EGDPhE > EGEE > EGME > EGPE > EGBE, EGHE, DGME and TGME, respectively. Further, [3 H]progesterone or [3 H]androstenedione binding affinities to the oocyte plasma membrane progesterone receptor (OMPR) or classical androgen receptor (AR) were: EGME > EGPhE ≥ PGPhE ≥ EGEE > EGBeE >> EGPE >> EGBE ≥ EGHE > EGDPhE, TGME, and DGME, or EGPhE > PGPhE >> EGBeE > EGDPhE >> EGEE ≥ EGME >> EGPE, EGBE, and EGHE > DGME and TGME, respectively. Binary joint mixture studies with the GVBD model using flutamide (AR antagonist) and EGPhE indicated that flutamide/EGPhE mixture acted in a concentration additive manner. The effects of substituted GE series, however, may be mediated through the OMPR; the potency of EGPhE may be the result of bimodal inhibition of both the OMPR and AR pathways.

Studies on the environmental fate, ecotoxicology and toxicology of 2-methyl 1,3-propanediol.

2-methyl 1,3-propandiol (MPD) is a low molecular weight, colorless glycol used in polymer and coating applications. The log Kow of -0.6 suggests partitioning to aqueous phases with a low concern for possible bioaccumulation. MPD was found to be inherently biodegradable. Ecotoxicological results in several aquatic and terrestrial species found no significant hazard potential. MPD is rapidly absorbed via the oral and dermal routes, metabolized to 3-hydroxybutyrate, and excreted in urine with a half-life of 3.6 h. Acute toxicity testing found low toxicity via all routes. Barely perceptible skin irritation was observed in human volunteers, whereas there was no evidence of irritation in rabbits. Skin sensitization in Guinea pigs was negative. Human skin patch results indicated minimal response in about 1% of individuals. There was no evidence of mutagenicity using bacterial and mammalian test systems. A 90-day oral study in rats found no adverse effects at any dose. Three developmental toxicity studies in rats and rabbits, found no treatment-related maternal toxicity, fetal toxicity or malformations. A two-generation reproduction study in rats found no consistent treatment-related adverse effects on reproduction in either generation. No carcinogenicity studies with MPD were identified. MPD presents a low degree of toxicological and ecotoxicological or environmental hazard.

Pyriculins A and B, two monosubstituted hex-4-ene-2,3-diols and other phytotoxic metabolites produced by Pyricularia grisea isolated from buffelgrass (Cenchrus ciliaris).

Pyricularia grisea has been identified as a foliar pathogen on buffelgrass (Cenchrus ciliaris) in North America and was studied as a potential source of phytotoxins for buffelgrass control. Two monosubstituted hex-4-ene-2,3-diols, named pyriculins A and B, were isolated from its culture filtrate organic extract together with (10S,11S)-(-)-epipyriculol, trans-3,4-dihydro-3,4,8-trihydroxy-1(2H)-napthalenone, and (4S)-(+)-isosclerone. Pyriculins A and B were characterized by spectroscopic (essentially nuclear magnetic resonance [NMR], High-resolution electrospray ionization mass spectrometry [HRESIMS]) and chemical methods such as (4E)-1-(4-hydroxy-1,3-dihydroisobenzofuran-1-yl)hex-4-ene-2,3-diols. The relative and absolute configuration of these compounds was determined by a combination of spectroscopic (NMR, electronic circular dichroism [ECD]) and computational tools. When bioassayed in a buffelgrass coleoptile and radicle elongation test, (10S,11S)-(-)-epipyriculol proved to be the most toxic compound. Seed germination was much reduced and slowed with respect to the control and radicles failed to elongate. All five compounds delayed germination, but only (10S,11S)-(-)-epipyriculol was able to prevent radicle development of buffelgrass seedlings. It had no effect on coleoptile elongation, while the other four compounds caused significantly increased coleoptile development relative to the control.

Margin of safety of pentylene glycol derived using measurements of cutaneous absorption and volatility.

The safety assessment of pentylene glycol (PG) has been based on a bioavailability extrapolated from those of other 1,2-glycols or an assumed 100% absorption. To make a better safety assessment and an accurate calculation of the margin of safety (MoS), the skin penetration of PG present in a commercially available sunscreen was measured in pig skin at different exposure durations. The mass balance of PG decreased with increasing exposure durations, from 98% (1 h) to 29% (24 h) and the amount of PG detected in the skin wash decreased over time from 93% to 3%. The decrease in mass balance was attributed to an unexpected volatility of PG, which was confirmed in additional experiments. The maximum bioavailable amount of PG was 123 µg/cm2 after 24 h and was considered to be worst case scenario (10 mg/cm2 i.e. 5-fold the recommended application standard dose, 2 mg/cm2). MoS values for the application of a standard dose of sunscreen after 1-24 h exposure were 140-671 in adults and, if calculated for children ratios, 87-217 Based on the available toxicological data for PG in comparison to the amounts determined to be potentially bioavailable, PG in the test sun protection product SPF 50 + does not show any safety concerns for daily usage at the recommended dosage of 2 mg/cm2 or lower.

Prenatal Exposure to Glycol Ethers and Neurocognitive Abilities in 6-Year-Old Children: The PELAGIE Cohort Study.

BACKGROUND: Glycol ethers (GE) are widely used organic solvents. Despite the potential neurotoxicity of several families of organic solvents, little is known about the impact of GE on the neurodevelopment of infants and children. OBJECTIVES: We investigated the relation between urinary concentrations of GE metabolites in pregnant women and neurocognitive abilities in their 6-year-old children in the PELAGIE mother-child cohort. METHODS: Five GE metabolites were measured in first morning void urine samples of 204 French pregnant women in early pregnancy (< 19 weeks of gestation). Psychologists assessed the neurocognitive abilities of their 6-year-old children with the Wechsler Intelligence Scale for Children IV (WISC) and the Developmental Neuropsychological Assessment (NEPSY). We analyzed the results with linear (WISC) and Poisson regression models (NEPSY), adjusted for potential confounders, including child's stimulation at home. RESULTS: GE metabolites were detected in 90-100% of maternal urine samples. The WISC Verbal Comprehension score was significantly lower for children with the highest tertile of urinary phenoxyacetic acid (PhAA) [ß (third vs. first tertile) = -6.53; 95% CI: -11.44, -1.62]. Similarly, the NEPSY Design Copying subtest score was lower in those with the highest tertile of urinary ethoxyacetic acid (EAA) [ß (third vs. first tertile) = -0.11; 95% CI: -0.21, 0.00]. The other GE metabolites we studied were not significantly associated with WISC or NEPSY scores. CONCLUSIONS: Prenatal urine concentrations of two GE metabolites were associated with lower WISC Verbal Comprehension Index scores and NEPSY Design Copying subscale scores, respectively, at age 6 years. PhAA is the primary metabolite of 2-phenoxyethanol (EGPhE), which is commonly found in cosmetics, and precursors of EAA are frequently used in cleaning agents. Additional research is needed to confirm our findings and further explore potential effects of prenatal GE exposures on neurocognitive performance in children.

Indoor air guide values for glycol ethers and glycol esters-A category approach.

The German Committee on Indoor Guide Values issues indoor air guide values to protect public health. For health evaluation of glycol ethers and glycol esters in air, the entire group of substances with data for 47 chemicals was analyzed in order to gain a consistent assessment. For some glycol ethers reproductive and hematological effects are of central interest, whereas for others effects on liver and kidneys are crucial. Moreover, some glycol ethers have also been shown to cause irritation of the respiratory tract. For 14 chemicals, suitable inhalation studies were available for deriving specific guide values, or analogies to closely related substances could be drawn. For these chemicals individual indoor air guide values were derived, the respective guide value I ranging from 0.02 to 2mg/m(3). Guide values were derived according to the procedures issued by the Committee, considering the exposure duration in indoor air compared to animal studies or the situation at workplaces, the duration of the respective study, species differences, and interindividual variability including special sensitivity of children. For glycol ethers with insufficient data default guide values II and I of 0.05 and 0.005ppm, respectively, were recommended based on statistical analyses of the available data on all glycol ethers and on evaluation of single studies. For evaluation of combined effects additivity is assumed.

Preservação da fertilidade e dos ovários em mulheres com tumores anexiais benignos / Preservation of the fertility and the ovaries in women with benign adnexal tumors

OBJETIVO: Avaliar a preservação da fertilidade e dos ovários em mulheres submetidas à cirurgia por tumor anexial benigno. MÉTODOS: Para este estudo observacional com coleta prospectiva foram incluídas 206 mulheres operadas no CAISM-Unicamp de fevereiro de 2010 a janeiro de 2014. A preservação da fertilidade foi definida como tumorectomia ou anexectomia unilateral sem histerectomia em mulheres na pré-menopausa. A preservação ovariana foi considerada quando pelo menos um ovário ou parte dele foi preservado. RESULTADOS: Das 206 mulheres com tumores anexiais benignos, 120 (58%) estavam na pré-menopausa e 86 (42%) na pós-menopausa. Na pré-menopausa, foram encontrados 36 (30%) tumores de células germinativas, 31 (26%) neoplasias epiteliais e 11 (9%) do cordão sexual e estroma. Na pós-menopausa foram identificados 35 (41%) neoplasias epiteliais, 27 (31%) do cordão sexual e estroma e 8 (9%) de células germinativas. Entre as 36 mulheres com tumores ovarianos não neoplásicos, 21 (58%) apresentavam endometriomas e 8 (22%) cistos funcionais. Das 22 mulheres com tumores extra ovarianos, o leiomioma uterino foi o achado mais frequente (50%). Entre as pacientes com ≤35 anos, 26 (57%) foram submetidas à tumorectomia e 18 (39%) a anexectomia unilateral com preservação do útero e anexo contralateral. Mulheres com ≤35 anos foram mais frequentemente operadas por laparoscopia que esteve associada a maior taxa de preservação de fertilidade quando comparada com a laparotomia (p<0,01). Observou-se que 26 das pacientes submetidas à histerectomia com anexectomia (28%) bilateral estavam na pré-menopausa. CONCLUSÕES: Embora se observe uma tendência em realizar apenas tumorectomia em mulheres com ≤35 anos, uma proporção significativa de mulheres jovens ainda é ...

PURPOSE: To evaluate the sparing of fertility and ovaries in women submitted to surgical treatment for benign adnexal tumors. METHODS: Between February 2010 and January 2014, 206 patients were included in this observational study as they were submitted to surgical treatment for benign ovarian tumors at CAISM, a tertiary hospital. Fertility sparing surgery was defined as tumorectomy or unilateral salpingoophorectomy without hysterectomy in premenopausal women. Preservation of the ovary occurred when at least one ovary or part of it was mantained. RESULTS: Of the 206 women with benign tumors, 120 (58%) were premenopausal and 86 (42%) were postmenopausal. There were 36 (30%) ovarian germ cell tumors, 31 (26%) epithelial neoplasms and 11 (9%) sex-cord stromal tumors among premenopausal women. In the group of postmenopausal women, 35 (41%) epithelial neoplasms, 27 (31%) sex-cord stromal tumors and 8 (9%) ovarian germ cell tumors were identified. Among 36 women with non-neoplastic ovarian tumors, 21 (58%) had endometriomas and 8 (22%) functional cysts. Among 22 women with extra-ovarian tumors, uterine leiomyomatosis was the most frequent finding (50%). In the group of women who were ≤35 years old, 26 (57%) were treated by tumorectomy and 18 (39%) were submitted to unilateral salpingoophorectomy with sparing of the uterus and the contralateral ovary. Women who were ≤35 years old were more frequently operated by laparoscopy which was associated with a higher number of fertility sparing procedures when compared to laparotomy (p<0.01). Twenty-six (28%) women submitted to hysterectomy with bilateral salpingoophorectomy were premenopausal. CONCLUSION: Although there is a trend to perform only tumorectomy in women who are ≤35 years old, a significant number of young women is still treated by salpingoophorectomy. Among 36- to 45-year-old women, only 70% had their fertility spared, while 20% had both ovaries removed. ...

Dual role of leukotriene B4 receptor type 1 in experimental sepsis.

BACKGROUND: The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis. METHODS: Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate. RESULTS: The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-α, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice. CONCLUSIONS: U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis.

Dieta y cáncer gástrico en México y en el mundo / Diet and gastric cancer in Mexico and in the world

El cáncer gástrico (CG) es la cuarta causa de muerte por cáncer a nivel global. La dieta y el consumo de alcohol y tabaco, además de la infección por Helicobacter pylori determinan un gran número de casos de esta neoplasia. Algunos alimentos contienen sustancias que podrían influir en el proceso de carcinogénesis gástrica, aunque los mecanismos subyacentes no están completamente dilucidados. En México y el mundo, la disminución en el consumo de frutas, vegetales no feculentos y allium, leguminosas y alimentos fuente de selenio, así como el aumento en el consumo de sal, alimentos salados, salmuera y ahumados, chile, carnes procesadas y asadas o a la parrilla se han asociado respectivamente con un aumento de riesgo de CG. Con la evidencia disponible, se podrían desarrollar y evaluar programas para la prevención y control del CG.

Gastric cancer (GC) is the fourt leading cause of cancer death at global level. Diet, alcohol and tobacco, in addition to Helicobacter pylori infection, account for a large number of cases. Some substances contained in foods may influence GC carcinogenesis process; however, the underlying mechanisms have not been fully elucidated. In Mexico and worldwide, a low intake of fruits, non-starchy and allium vegetables, pulses, and foods containing selenium, as well as high intake of salt, salty, salted and smoked foods, chili pepper, processed and grilled/barbecued meats, have been respectively associated with an increased risk of GC. Based on the available evidence, programs for GC prevention and control could be developed and evaluated.

Occupation exposures and sperm morphology: a case-referent analysis of a multi-centre study.

OBJECTIVE: We examined occupational exposures and sperm morphology to establish whether exposures implicated differed from those affecting motile sperm concentration. METHODS: Computer aided sperm morphometric assessment was undertaken on morphology slides obtained as part of a multi-centre study in 1999-2002 of occupational factors in male infertility. Men attending 14 fertility clinics across the UK were recruited and gave a semen sample. Before results of the semen analysis were known, the men completed detailed questionnaires about their employment and lifestyle. Occupational exposures were assessed by occupational hygienists. Data were analysed using an unmatched case-referent design, allowing for clustering and for confounders. Three case definitions were used: poor morphology (normal morphology <4%), low motile sperm count (MSC) (<4.8×10(6)) and either condition. RESULTS: Morphology results were available for 1861/2011 men employed at the time of recruitment. Of these 1861, 296 (15.9%) had poor morphology; of the 2011with sperm count, 453 (22.5%) had low MSC; 654/1981 (33.0%) had either condition. Poor morphology, adjusted for confounding, was related to self-reported lifetime exposure to lead (OR=1.33; 95% CI 1.00 to 1.75). Low MSC was also related to self-reported lead and to hygienist-assessed glycol ether exposure. Self-reported use of paint stripper (OR=1.47; 95% CI 1.07 to 2.03) and lead, but not glycol ether, were significantly related to the combined case definition. CONCLUSIONS: While this study did not identify any occupational exposure uniquely related to sperm morphology, the capacity of the study to detect risk was increased by including morphology with sperm concentration and motility.

Safety assessment of 1,2-glycols as used in cosmetics.

Caprylyl glycol and related 1,2-glycols are used mostly as skin and hair conditioning agents and viscosity agents in cosmetic products, and caprylyl glycol and pentylene glycol also function as cosmetic preservatives. The Cosmetic Ingredient Review (CIR) Expert Panel noted that, while these ingredients are dermally absorbed, modeling data predicted decreased skin penetration of longer chain 1,2-glycols. Because the negative oral toxicity data on shorter chain 1,2-glycols and genotoxicity data support the safety of the 1,2-glycols reviewed in this safety assessment, the Panel concluded that these ingredients are safe in the present practices of use and concentration described in this safety assessment.

A validated GC-MS procedure for fast, simple, and cost-effective quantification of glycols and GHB in human plasma and their identification in urine and plasma developed for emergency toxicology.

Methods developed for use in emergency toxicology have to be fast and simple. Additionally, such methods should be multi-analyte procedures because they allow monitoring of analytes of different drug classes in one single body sample. This is important because often only a limited amount of sample is available and the results have to be reported as fast as possible. Therefore, we describe the improvement of an existing method published by van Hee at al. The new method is fast and simple and designed for the simultaneous determination of ethylene glycol, 1,2-propylene glycol, lactic acid, glycolic acid, gamma-hydroxybutyric acid (GHB), diethylene glycol, triethylene glycol, and tetraethylene glycol in human plasma or urine. A 50-µL aliquot of sample was deproteinized and 20 µl of the diluted specimen were derivatized using bis-N,O-trimethylsilyl trifluoroacetamide and the catalyst dimethylformamide. After microwave-assisted derivatization, an aliquot was injected into the gas chromatograph and analyzed with electron ionization mass spectrometry in selective ion monitoring mode. All compounds are separated within 12 min and detected with a limit of quantification of 0.05 and 0.01 g/L for glycols and GHB, respectively. Calibration was linear from 0.05 to 1.0 g/L for glycols and 0.01 to 0.2 g/L for GHB. Validation criteria were shown to be in the required limits with exception of lactic acid. Average analysis time from starting sample preparation until quantitative plasma results of approximately 35 min was achieved. This turnaround time is considered most appropriate for emergency cases.

Properties of a new mouthrinse for patients receiving radiation therapy.

INTRODUCTION: Patients receiving radiation therapy due to oral cancer develop complications such as hyposalivation, mucositis, oral infections, dental hypersensitivity and caries. Mouthrinses can alleviate some of these problems. AIMS AND OBJECTIVES: To investigate the in vitro antimicrobial properties and cytotoxicity of an experimental mouthrinse. METHODS: The mouthrinse contained 30% hexylene glycol (glycerine), 7% potassium nitrate and 0.025% sodium fluoride. The minimal inhibitory concentration (MIC) of these ingredients and the mixture was determined for C. albicans, S. aureus and S. mutans over 24 hours at different concentrations. The MICs of two commercial mouthrinses, Corsodyl and Plax, were also determined using the same organisms. All mouthrinses were then tested to determine the percentage kill over 1, 2, and 3 minutes. RESULTS: The MICs for hexylene glycol were 10%, 30% and 10% for C. albicans, S. aureus and S. mutons respectively. Potassium nitrate and sodium fluoride had no antimicrobial effects. The MIC of Corsodyl was 0.016 mg/ml for all the test organisms. The MIC for Plax varied from 0.0002 mg/ml to 0.001 mg/ml. The kill rates for all mouthrinses were acceptable, with no statistical differences between them. The experimental mouthrinse was not toxic to human oesophageal SCC cells after 1 minute exposure. At the time of the experiment, the costs of a similar quantity of the experimental mouthrinse, Corsodyl and Plax were R5.24, R30.00 and R10.00 respectively. CONCLUSIONS: The experimental mouthrinse was cost-effective and proved to have an antimicrobial effect and could be used safely to alleviate oral infections, desensitize teeth, improve oral hygiene and control dental caries in cancer patients after radiation therapy.

Cartilage tissue engineering for auricular reconstruction: in vitro evaluation of potential genotoxic and cytotoxic effects of scaffold materials.

Tissue engineering of autologous cartilage transplants is suggested as a new approach in reconstruction of external auricular deformities. 1.6-Hexanediol (HD), 1.8-diazabicyclo[5.4.0]undec-7-ene (DBU) and 6-hydroxyhexanoic acid (HHA) are matrices of the open-pored polyurethane three-dimensional scaffold. Since these bioresorbable materials may interact with the human organism, cytotoxic effects on human chondrocytes and lymphocytes and genotoxic effects on human lymphocytes were monitored. Staining with propidium iodide and fluorescence diacetate as well as the EZ4U proliferation assay served for the detection of cytotoxic effects of the materials on human chondrocytes. Trypan blue staining was used to monitor cytotoxicity on lymphocytes. Genotoxic effects on lymphocytes in terms of strand breaks, alkali labile sites and incomplete excision repair were determined by the alkaline single cell microgel electrophoresis (Comet) assay. Cytotoxic effects in chondrocytes and lymphocytes as well as genotoxic effects in lymphocytes were dose-dependent with threshold values of 5mg/mL HD, 0.5mg/mL DBU and 0.03 mg/mL HHA showing no effects. These data suggest that these matrices could be safely used for scaffolds made of polyurethane unless these compounds are not released at a rate giving higher concentrations at the site of implantation or in body fluids, respectively.

Safety of a preservative system containing 1,2-hexanediol and caprylyl glycol.

To study the potential for delayed Type IV dermal sensitivity of a new preservative system containing 1,2-hexanediol and caprylyl glycol, 200-subject repeat insult patch tests were performed with a 15% mixture of 1,2-hexanediol and caprylyl glycol (equal parts of the 2 ingredients) in carbomer gel and a cosmetic formulation at an actual use concentration. No delayed Type IV hypersensitivity reactions were observed.

Relative developmental toxicity of glycol ether alkoxy acid metabolites in the embryonic stem cell test as compared with the in vivo potency of their parent compounds.

The embryonic stem cell test (EST) has been proposed as an in vitro assay that might reduce animal experimentation in regulatory developmental toxicology. So far, evaluation of the EST was not performed using compounds within distinct chemical classes. Evaluation within a distinct class of chemically related compounds can define the usefulness of the assay for the chemical class tested. The aim of the present study was to evaluate the relative sensitivity of the EST for a selected series of homologous compounds and to compare the data to the relative developmental toxicity of the compounds in vivo. To this end a series of proximate developmentally toxic glycol ether alkoxy acid metabolites was tested in the EST. All glycol ether alkoxy acid metabolites tested showed a concentration-dependent inhibition of cardiomyocyte differentiation at noncytotoxic concentrations, with methoxyacetic acid as the most potent compound followed by ethoxyacetic acid, butoxyacetic acid, and phenoxyacetic acid, respectively. The potency ranking of the compounds in the EST corresponds with the available in vivo data. The relative differences between the potencies of the compounds appeared more pronounced in the in vivo studies than in the EST. A possible explanation for this discrepancy could be the difference in the kinetics of the compounds in vivo as compared with their in vitro kinetics. This study illustrates that the EST can be used to set priorities for developmental toxicity testing within classes of related compounds.