Propylene Glycol Toxicity in a Pediatric Patient: The Dangers of Diluents

2000 ◽  
Vol 13 (3) ◽  
pp. 214-225 ◽  
Author(s):  
James O'Donnell ◽  
Sue Lyon Mertl ◽  
William N. Kelly
Keyword(s):  
Propylene Glycol ◽  
Expert Witness ◽  
Skin Irritation ◽  
Toxicity Testing ◽  
Oral Solution ◽  
New Drugs ◽  
Burn Victims ◽  
Competitive Interference ◽  
Lactate Levels ◽  
Child Subject

This report will present a case of neonatal propylene glycol poisoning from the use of intravenous lorazepam and also discuss the toxicity of diluents in general. Although used as a diluent in many pharmaceuticals and generally considered safe, propylene glycol can cause serious side effects: hyperosmolality in burn victims due to silver sulfadiazine products containing propylene glycol and in premature babies due to particular multivitamin preparations, irreversible perception deafness, skin irritation, high anion gap acidosis due to elevated lactate levels, and reversible neurological disturbances. Toxicity caused by propylene glycol may be manifested by hyperosmolality, lactic acidosis, hemolysis and hemoglobinuria, skin irritation, deafness, and other neurological disturbances.1 Historically, the toxicity of diluents played an important role in the development of toxicity testing before the release of new drugs. The topic is current, as evidenced by the Important Drug Warning letter recently issued by Glaxo Wellcome, the manufacturer of Agenerase, warning about the toxicities and drug interactions associated with the propylene glycol diluent in the oral solution, as well as by competitive interference with the aldehyde dehydrogenase enzyme pathway. This report and discussion is included in the Forensic Pharmacist issue because the case investigation arose out of retention of one of the authors (O'Donnell) as an expert witness and consultant on behalf of the child/subject of the case report.

5 Final Report on the Safety Assessment of Propylene Glycol Stearate and Propylene Glycol Stearate Self-Emulsifying

1983 ◽  
Vol 2 (5) ◽  
pp. 101-124 ◽  
Keyword(s):  
Propylene Glycol ◽  
Safety Assessment ◽  
Animal Studies ◽  
Skin Irritation ◽  
Final Report ◽  
Cosmetic Products ◽  
Dermal Toxicity ◽  
Cosmetic Ingredients ◽  
Available Information

Propylene Glycol Stearates (PGS) are a mixture of the mono- and diesters of triple-pressed stearic acid and propylene glycol and are used in a wide variety of cosmetic products. Studies with 14C-labeled PGS show that it is readily metabolized following ingestion. In rats, the acute oral LD50 has been shown to be approximately 25.8 g/kg. The raw ingredient produced no significant dermal toxicity, skin irritation, or eye irritation in acute tests with rabbits. Subchronic animal studies produced no evidence of oral or dermal toxicity. Propylene glycol monostea-rate was negative in in vitro microbial assays for mutagenicity. In clinical studies, PGS produced no significant skin irritation at concentrations up to 55% nor skin sensitization on formulations containing 2.5%. Photo-contact allergenicity tests on product formulations containing 1.5% PGS were negative. From the available information, it is concluded that Propylene Glycol Stearates are safe as cosmetic ingredients in the present practices of use.

scholarly journals Evaluation of the antimicrobial activity and safety of Rhus vulgaris (Anacardiaceae) extracts

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Angela Mutuku ◽  
Lizzy Mwamburi ◽  
Lucia Keter ◽  
Joyce Ondicho ◽  
Richard Korir ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Antimicrobial Activity ◽  
Methanol Extract ◽  
Skin Irritation ◽  
Toxicity Testing ◽  
Oral Toxicity ◽  
Traditional Use ◽  
One Way Anova

Abstract Background Medicinal plants have been used in the treatment of various ailments in most developing countries. Oral infections are the most prevalent diseases in man. The Rhus family has been found to have antimicrobial, antimalarial, and anti-inflammatory properties. Few studies have been done on Rhus vulgaris Meikle. A study was conducted to determine the effect of Rhus vulgaris Meikle stem bark extracts against selected oral pathogenic microorganisms and the safety of the extracts in vitro and in vivo. Methods Methanol:dichloromethane (1:1), methanol and aqueous extracts were tested for bacteriostatic and bactericidal effects against Methicillin Resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Streptococcus mutans and Candida albicans. Cytotoxicity of the active extracts was determined using Vero E6 cell lines while safety was evaluated in mice and rats. Phytochemical screening was performed on the methanol extracts. One-way ANOVA and Tukey’s multiple comparisons tests were performed using IBM SPSS statistics 20.0 for antimicrobial assay and acute toxicity testing. One-way ANOVA and Dunnett’s multiple comparison tests were conducted using GraphPad Prism 8.0 for cytotoxicity assay. Results Methanol extract of Rhus vulgaris showed significant antimicrobial activity against MRSA (12.00 ± 0.00 mm; p-value of < 0.005; Minimum Inhibitory Concentration of 0.391 mg/ml; Minimum Bactericidal Concentration of 1.563 mg/ml). The extract were not cytotoxic at 100 μg/ml which was the highest tested concentration. In acute dermal irritation testing, the methanol extract resulted in mild irritation with erythema and flaking that cleared within 8 days. There were no observable adverse effects from oral administration of the extracts (acute oral toxicity testing) at concentrations of 50 mg/kg, 300 mg/kg and 2000 mg/kg. Tannins, saponins, flavonoids, terpenoids, glycosides, alkaloids and phenols were detected in the methanol extract. Conclusions Antimicrobial activity of R. vulgaris extracts supports its traditional use as a toothbrush. Cytotoxicity demonstrated by the extracts as well as the mild skin irritation warrants further study before R. vulgaris can be recommended for the development of effective and safe mouthwashes.

scholarly journals Final Report on the Safety Assessment of Propylene Glycol (PG) Dicaprylate, PG Dicaprylate/Dicaprate, PG Dicocoate, PG Dipelargonate, PG Isostearate, PG Laurate, PG Myristate, PG Oleate, PG Oleate SE, PG Dioleate, PG Dicaprate, PG Diisostearate, and PG Dilaurate

1999 ◽  
Vol 18 (2_suppl) ◽  
pp. 35-52 ◽  
Author(s):  
Wilbur Johnson
Keyword(s):  
Polyethylene Glycol ◽  
Propylene Glycol ◽  
Skin Irritation ◽  
Skin Penetration ◽  
Final Report ◽  
Limited Data ◽  
Oral Toxicity ◽  
Cosmetic Ingredients ◽  
Cosmetic Formulations ◽  
Safety Assessments

The Propylene Glycol Dicaprylate family of ingredients includes several esters and diesters of Propylene Glycol and fatty acids. These ingredients are used in cosmetic formulations as skin conditioning agents, viscosity increasing agents, and surfactants. Two skin irritation studies (minimal to no irritation) and a comedogenicity study (insignificant comedogen) on Propylene Glycol Dicaprylate/Dicaprate and a skin irritation study (slight) and an acute oral toxicity study (nontoxic) on Propylene Glycol Laurate were available. Available data were also found indicating that Propylene Glycol Dicaprylate/Dicaprate and Propylene Glycol Dipelargonate may enhance the skin penetration of other chemicals. Because of the ability of these Polyethylene Glycol esters and diesters to enhance penetration of other agents, it was recommended that care be taken in using these and other Polyethylene Glycol esters and diesters in cosmetic products. Previous Cosmetic Ingredient Review safety assessments of related ingredients, including Polyethylene Glycol, Polyethylene Glycol Stearate, Coconut Oils and Acids, Isostearic Acid, Lauric Acid, Myristic Acid, Oleic Acid, and Caprylic/Capric Triglyceride, were summarized. Included were mutagenicity, chronic toxicity, and skin irritation and sensitization data. Based in part on the limited data available on the ingredients included in the report, but more so on the previous reviews of chemically similar moieties, it was concluded that Propylene Glycol Dicaprylate, Propylene Glycol Dicaprylate/Dicaprate, Propylene Glycol Dicocoate, Propylene Glycol Dipelargonate, Propylene Glycol Isostearate, Propylene Glycol Laurate, Propylene Glycol Myristate, Propylene Glycol Oleate, Propylene Glycol Oleate SE, Propylene Glycol Dioleate, Propylene Glycol Dicaprate, Propylene Glycol Diisostearate, and Propylene Glycol Dilaurate are safe for use as cosmetic ingredients in the present practices of use.

scholarly journals Feasibility of intravitreal injections and ophthalmic safety assessment in marmoset (Callithrix jacchus) monkeys

2017 ◽  
Vol 4 (1) ◽  
pp. 93-100
Author(s):  
Birgit Korbmacher ◽  
Jenny Atorf ◽  
Stephanie Fridrichs-Gromoll ◽  
Marilyn Hill ◽  
Sven Korte ◽  
...  
Keyword(s):  
Cynomolgus Monkey ◽  
Toxicity Testing ◽  
Common Marmoset ◽  
Callithrix Jacchus ◽  
Study Data ◽  
New Drugs ◽  
Intravitreal Injections ◽  
Ocular Toxicity ◽  
Toxicological Studies ◽  
The Common

Abstract. To safeguard patients, regulatory authorities require that new drugs that are to be given by the intravitreal (IVT) route are assessed for their safety in a laboratory species using the same route of administration. Due to the high similarity of ocular morphology and physiology between humans and nonhuman primates (NHPs) and due to the species specificity of many biotherapeutics, the monkey is often the only appropriate model. To this end, intravitreal administration and assessment of ocular toxicity are well established in cynomolgus monkeys (Macaca fascicularis). In contrast, the common marmoset monkey (Callithrix jacchus) is not a standard model for ocular toxicity studies due to its general sensitivity to laboratory investigations and small eye size. It was the purpose of the present work to study whether the marmoset is a useful alternative to the cynomolgus monkey for use in intravitreal toxicological studies. Six marmoset monkeys received repeated (every 2 weeks for a total of four doses) intravitreal injections of 10 or 20 µL of a placebo. The animals were assessed for measurements of intraocular pressure (IOP), standard ophthalmological investigations and electroretinography (ERG). At the end of the dosing period, the animals were sacrificed and the eyes were evaluated histologically. ERG revealed similar results when comparing predose to end-of-study data, and there was no difference between the two dose volumes. A transient increase in the IOP was seen immediately after dosing, which was more pronounced after dosing of 20 µL compared to 10 µL. Ophthalmologic and microscopic observations did not show any significant changes. Therefore, it can be concluded that 10 µL as well as 20 µL intravitreal injections of a placebo are well tolerated in the marmoset. These results demonstrate that the common marmoset is an alternative to the cynomolgus monkey for intravitreal toxicity testing.

Acute Toxicity Studies of Xerox Reprographic Toners

1994 ◽  
Vol 13 (1) ◽  
pp. 2-20 ◽  
Author(s):  
George H. Y. Lin ◽  
Robert Mermelstein
Keyword(s):  
Acute Toxicity ◽  
Skin Irritation ◽  
Toxicity Testing ◽  
Inhalation Toxicity ◽  
Thermoplastic Polymer ◽  
Test Results ◽  
Dermal Toxicity ◽  
Oral Toxicity ◽  
Toxicity Studies

Typical reprographic toners consist of a thermoplastic polymer or polymers as the major component, a colorant or colorants (carbon black or color pigments), and small quantities of additives such as charge control and/or lubricating/release agents. Another type of toner contains iron oxides and polymers) as the major components. As a complement to the recently published Xerox chronic inhalation studies of toners, we are reporting the acute toxicity studies of some typical Xerox toners. The studies include acute oral toxicity in rats, acute dermal toxicity in rabbits, acute inhalation toxicity in rats, eye irritation in rabbits, skin irritation in rabbits, skin sensitization in guinea pigs, and the repeated-insult patch test in humans. These studies represent our acute toxicity testing using different protocols with various toners carried out during the period 1969–1984. In addition, we recently carried out acute dermal toxicity testing at 5 g/kg with two representative toners, for the purpose of classification of waste toners in the State of California. The test results consistently indicate that all toners were practically nontoxic: oral LD50 from <5 to <35 g/kg; dermal LD50 from <2 to <5 g/kg; and inhalation LC50 (4 h) from <0.17 to <10.2 g/m3. They were nonirritating to the eye and nonirritating/ nonsensitizing to the skin.

Final Report on the Safety Assessment of Propylene Glycol and Polypropylene Glycols

1994 ◽  
Vol 13 (6) ◽  
pp. 437-491 ◽  
Keyword(s):  
Propylene Glycol ◽  
Propylene Oxide ◽  
Animal Studies ◽  
Skin Irritation ◽  
Reproductive Toxicity ◽  
Normal Subjects ◽  
Final Report ◽  
Polypropylene Glycol ◽  
Wide Range ◽  
Fetal Malformations

Propylene Glycol is an aliphatic alcohol manufactured as a reaction product of propylene oxide and water. Polypropylene Glycol is a polymer formed by adding propylene oxide to dipropylene glycol. Propylene Glycol is reportedly used as a skin-conditioning agent-humectant, solvent, viscosity-decreasing agent, and humectant in thousands of cosmetic formulations. Polypropylene Glycols of various polymer lengths are reportedly used as miscellaneous skin-conditioning agents in far fewer formulations. Acute, subchronic, and short-term animal studies suggested little toxicity beyond slight growth and body weight decreases. Little ocular or skin irritation was observed in animal studies, and no sensitization was seen. Small increases in fetal malformations were seen in mice injected subcutaneously with Propylene Glycol, but a continuous breeding reproduction study in mice showed no reproductive toxicity following oral administration. A wide range of mutagenesis assays were negative, and studies in mice and rats showed no evidence of carcinogenesis. Clinical data showed skin irritation and sensitization reactions in Propylene Glycol in normal subjects at concentrations as low as 10% under occlusive conditions and dermatitis patients at concentrations as low as 2%. A careful evaluation of skin irritation and sensitization data as a function of disease state of the individual, occlusion, and concentration was done. On the basis of that analysis, it is concluded that Propylene Glycol and Polypropylene Glycol are safe for use in cosmetic products at concentrations up to 50%.

scholarly journals Zebrafish as a model system for biomedical studies

2010 ◽  
Vol 56 (1) ◽  
pp. 120-131 ◽  
Author(s):  
N.F. Belyaeva ◽  
V.N. Kashirtseva ◽  
N.V. Medvedeva ◽  
Yu.Yu. Khudoklinova ◽  
O.M. Ipatova ◽  
...  
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Developmental Disorders ◽  
Model Organism ◽  
Toxicity Testing ◽  
New Drugs ◽  
Human Diseases ◽  
Research Model ◽  
Drug Discovery And Development ◽  
Phospholipid Nanoparticles

Zebrafish (Danio rerio) are now firmly established as a powerful research model for many areas of biology and medicine. Here, we review some achievements of zebrafish - based assays for modeling human diseases and for drug discovery and development. For drug discovery, zebrafish are especially valuable in the earlier stages of research as they provide a model organism to demonstrate a new treatment's efficacy and toxicity before more costly mammalian models are used. This review provides examples of compounds known to be toxic to humans that have been demonstrated to functional similarly in zebrafish. Major advantages of zebrafish embryons are that they are readily permeable to small molecules added to their incubation medium and the transparent chorion enables the easy observation of development. Assay of acute toxicity (LC50 estimation) in embryos can also include the screening for developmental disorders as an indicator of teratogenic effects. We used zebrafish for toxicity testing of new drugs on the base of phospholipid nanoparticles. The organization of the genome and the pathways controlling signal transduction appear to be highly conserved between zebrafish and humans that allow using zebrafish for modeling of human diseases some examples of which are illustrated in this paper.

DESIGN OF EARLY CLINICAL TRIALS FOR NEW CONTRACEPTIVE METHODS

1974 ◽  
Vol 77 (1_Suppla) ◽  
pp. S266-S278
Author(s):  
Daniel R. Mishell ◽  
Harold A. Nash
Keyword(s):  
Clinical Trials ◽  
Large Scale ◽  
Clinical Investigation ◽  
Toxicity Testing ◽  
Field Trials ◽  
New Drugs ◽  
Animal Testing ◽  
Good Continuation ◽  
Large Scale Field ◽  
Pharmaceutical Agents

ABSTRACT A plan is outlined to shorten the current suggested duration of animal testing prior to clinical investigation with certain types of pharmaceutical agents. For many new drugs, especially steroids, after a pharmacologic profile is established, long term toxicity testing can usually be shortened prior to initiation of 6 months clinical trials involving about 1000 women. Clinical trials of this magnitude usually correlate very well with ultimate performance of contraceptive drugs, provided proper selection of subjects is performed with resultant good continuation rates. It is thus possible with certain new antifertility candidates to safely shorten the duration of both toxicological and clinical studies before initiating large scale field trials.

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