bluuebunny/crossref_metadata_2025 huggingface dataset:
Vigabatrin in Pediatric Epilepsy—An Open Study
Authors: Uldall Peter , Alving Jorgen , Gram Lennart , Beck Simon
Published: September 2009

The antiepileptic effect of vigabatrin in adults has been demonstrated in a number of controlled studies. In children, the effect of vigabatrin has been investigated only to a limited extent. In order to assess the long-term effect and safety of vigabatrin in patients with severe epilepsy, an open, add-on, dose-ranging study was initiated. To date, 27 children with partial epilepsy, two with generalized epilepsy, two with Lennox-Gastaut syndrome, and one with nonclassifiable epilepsy have been enrolled in the trial. Fifty-four percent of patients have experienced a greater than 50% reduction in seizure frequency, and four patients have become seizure free. A significant reduction in seizures was noted across the patient population, although patients who were recorded as seizure free at 3 and 6 months did suffer some recurrence of seizures. However, when seizures recurred, they did so at much lower frequency than recorded at the start of the study. Thirteen patients (39%) reported adverse events attributable to vigabatrin; one was immediately withdrawn from the study, and six had their vigabatrin dose reduced. No physiologic effects were noted on normal growth or clinical physical examination. (J Child Neurol 1991;6(Suppl):2S38-2S44).
Neurometabolic Diseases at a National Referral Center: Five Years Experience at the King Faisal Specialist Hospital and Research Centre
Authors: Ozand Pinar T. , Devol Edward B. , Gascon Generoso G.
Published: September 2009

Of 910 children under the age of 12 years referred to the national center, we were able to assign an etiology to 473 (52%). This group consisted of lysosomal storage diseases (32%), amino acid disorders (14%), organic acid disorders (16%), various chromosome abnormalities and syndromes with dysmorphia or brain dysgenesis (26%), and various other metabolic diseases (12%). While such amino acidemias as branched-chain amino acidemia (MSUD) in classic and intermediate forms (44%) and hyperphenylalaninemia (PKU) due to 6-pyruvoyltetrahydropterin synthase deficiency (6PTSD) (19%) were common, classic PKU was rare (16%). Methylmalonic acidemia (31%), 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (16%), and propionic acidemia (12%) were encountered more frequently than other types of organic acidemias. When compared to the number of referred Down's syndrome patients, the results suggested the birth of at least one infant with neurometabolic disease per 50 births. Five tribes of Saudi Arabia constituted 26% of the diagnosable neurometabolic diseases. Diseases such as MSUD, 6 PTSD, Sanfilippo syndrome type B, methylmalonic acidemia, homocystinuria, GM2 gangliosidosis Sandhoff variant, infantile central nervous system spongy degeneration (Canavan disease), and neuraminidase deficiency showed definite tribal occurrence. In addition, 32% to 42% of the definitely diagnosed, and 25% to 87% of patients with probable neurometabolic disease but without a definable etiology, had more than one sibling affected. It is concluded that the many rare autosomal diseases of Saudi Arabia are due to "founder effect" created by marriages occurring within tribal and extended family boundaries. (J Child Neurol 1992;7(Suppl):S4-S11).
Heterogeneity of Carboxypeptidase Activity in Infantile-Onset Galactosialidosis
Authors: Ozand P.T. , Gascon G.G.
Published: September 2009

The clinical presentation and laboratory findings in seven patients with neonatal/infantile-onset galactosialidosis are presented. We detected no carboxypeptidase activity in two of these patients, while an enzyme with different apparent Km, or both Km and Vm, were found in five others. We could not establish a correlation between the biochemical characteristics of carboxypeptidase and the age of onset, progression, or other clinical features of galactosialidosis. (J Child Neurol 1992;7(Suppl):S31-S40).
Treatment of Inherited Neurometabolic Diseases: The Future
Authors: Ozand Pinar T. , Gascon Generoso G.
Published: September 2009

The past 10 years' experience with bone marrow transplantation from normal, immunologically compatible donors indicates its possible use in various neurometabolic diseases, particularly in a patient who has not suffered irreparable brain damage. This experience may be a prelude to treatment by somatic gene therapy. This can be applied as an autologous bone marrow transplant, grafting the patient's own stem cells inserted with the normal gene. Although somatic gene therapy will be relatively easy for tissues with dividing cells, its application to target tissues with little or no cell division may pose difficulties. Meanwhile, techniques for the preservation, culture, and grafting of fetal neurons in humans have been developed and have been used in the treatment of Parkinson's disease. These procedures could readily be transferred to the treatment of other neurodegenerative diseases that cause significant morbidity, but ethical, legal, and religious considerations must be taken into account. All these efforts promise novel and improved management of inborn neurometabolic errors. (J Child Neurol 1992;7(Suppl):S132-S140.)
Developmental Principles of Antiepileptic Drug Therapy
Authors: Gilman Jamie T.
Published: September 2009

Antiepileptic drug therapy in children can be challenging because seizure semiology and drug disposition change dramatically over time. Close monitoring of drug clearance is required in early life because of the rapid ontogenesis of drug-eliminating organs. Large variations in serum peak and trough antiepileptic drug concentrations increase the risk for both adverse drug effects and unsatisfactory seizure control. Antiepileptic drug adverse effects also differ, probably relative to different receptor sensitivities in children. Failure to appreciate the developmental differences between children and adults can result in medication noncompliance, breakthrough seizures, and unacceptable adverse effects. (J Child Neurol 1994;9(Suppl):S20-S25).
Functional Neuroimaging With SPECT in Children With Partial Epilepsy
Authors: Harvey A. Simon , Berkovic Samuel F.
Published: September 2009

Single-photon emission computed tomography (SPECT) is being used increasingly in the investigation of children with intractable partial seizures. SPECT imaging of regional cerebral blood flow with 99mTc-hexamethylpropylene amine oxime, iodinated radiopharmaceuticals, and 133Xe typically reveals decreased cortical perfusion interictally and increased cortical perfusion ictally in the region of the epileptic focus. Studies in both adults and children indicate significantly greater sensitivity and specificity with ictal injection of radiopharmaceutical, with interictal SPECT not infrequently revealing nonlocalizing or falsely localizing information. Recent SPECT studies employing iodinated neuroreceptor ligands report altered receptor binding in the region of the epileptic focus, providing insight into the underlying neuropharmacology of partial epilepsy. SPECT has an established role in the presurgical localization of seizure foci in children with intractable partial seizures and may be a useful modality to study the functional anatomy and clinical semiology of partial seizures in childhood. (J Child Neurol 1994;9(Suppl):S71-S81).
The Role of PET in Childhood Epilepsy
Authors: Chugani Harry T.
Published: September 2009

Functional brain imaging with positron emission tomography (PET) has led to significant advances in the diagnosis and management of various forms of childhood epilepsy. Interictal PET in temporal lobe epilepsy typically shows decreased glucose utilization (hypometabolism) in one or both temporal lobes. Children with early-onset refractory extratemporal lobe epilepsy who do not manifest structural abnormalities on magnetic resonance imaging often show single or multiple cortical foci of hypometabolism indicating underlying microdysgenesis that corresponds to the area of epileptogenicity. The findings of focal cortical metabolic lesions and metabolic activation of subcortical structures (brain stem and lenticular nuclei) in patients with infantile spasms have allowed many infants with intractable spasms to be treated surgically with cortical resection, and have altered our concepts regarding the pathophysiology of these seizures. New observations in Lennox-Gastaut syndrome, Sturge-Weber syndrome, tuberous sclerosis, hemimegalencephaly, Landau-Kleffner syndrome, and other pediatric epilepsy syndromes have been documented with PET and have improved our understanding of these disorders. Recent PET studies of several neurotransmitter receptors in adult epileptic patients suggest that this approach holds great promise in the study of childhood epilepsy. The current guidelines indicating which patients with epilepsy should be referred for a PET study are outlined. (J Child Neurol 1994;9(Suppl):S82-S88).
Future Directions in Pediatric Epileptology
Authors: Blume Warren T.
Published: September 2009

Rapid developments in several areas of epileptology alter or clarify concepts and bring new hope to epileptic patients and their associates. Brief discussions of such advances comprise this report. Experimental and clinical data concerning the pathogenesis of cognitive impairment in some epileptic conditions are reviewed. Epidemiologic studies have altered some long-held concepts concerning etiology of seizures in early life. Molecular genetic studies have disclosed abnormalities in some of the epilepsies: a genetic predisposition to epilepsy may explain why some patients with cortical lesions develop seizures and others do not. It is suggested that many questions regarding surgery in pediatric epilepsy will be resolved only by more reliable techniques of case selection and follow-up. Practitioners in developed countries must realize how rudimentary is the care given to the unfortunate many with seizure disorders in less advantaged areas. (J Child Neurol 1994;9(Suppl)2S74-2S78).
Antiepileptic Drug Cellular Mechanisms of Action: Where Does Lamotrigine Fit In?
Authors: Coulter Douglas A.
Published: September 2009

Current frontline antiepileptic drugs tend to fall into several cellular mechanistic categories, and these categories often correlate with the clinical spectrum of action of the various antiepileptic drugs. Many antiepileptic drugs effective in control of partial and generalized tonic-clonic seizures are use- and voltage-dependent blockers of sodium channels. This mechanism selectively dampens pathologic activation of sodium channels, without interacting with normal sodium channel function. Examples include phenytoin, carbamazepine, valproic acid, and lamotrigine. Many antiepileptic drugs effective in control of generalized absence seizures block low threshold calcium currents. Low threshold calcium channels are present in high densities in thalamic neurons, and these channels trigger regenerative bursts that drive normal and pathologic thalamocortical rhythms, including the spike wave discharges of absence seizures. Examples include ethosuximide, trimethadione, and methsuximide. Several antiepileptic drugs that have varying clinical actions interact with the γ-aminobutyric acid (GABA)ergic system. Diazepam and clonazepam selectively augment function of a subset of GABA A receptors, and these drugs are broad-spectrum antiepileptic drugs. In contrast, barbiturates augment function of all types of GABAA receptors, and are ineffective in control of generalized absence seizures, but effective in control of many other seizure types. Tiagabine and vigabatrin enhance cerebrospinal levels of GABA by interfering with reuptake and degradation of GABA, respectively. These antiepileptic drugs are effective in partial seizures. Lamotrigine is effective against both partial and generalized seizures, including generalized absence seizures. Its sole documented cellular mechanism of action is sodium channel block, a mechanism shared by phenytoin and carbamazepine. These drugs are ineffective against absence seizures. Consequently, unless there are unique aspects to the sodium channel block by lamotrigine, it seems unlikely that this mechanism alone could explain its broad clinical efficacy. Therefore, lamotrigine may have as yet uncharacterized cellular actions, which could combine with its sodium channel blocking actions, to account for its broad clinical efficacy. (J Child Neurol 1997;12(Suppl 1):S2-S9).
Pediatric Use of Intravenous and Intramuscular Phenytoin: Lessons Learned
Authors: Wheless James W.
Published: September 2009

First developed in 1950, parenterally administered phenytoin offered substantial advantages over parenterally administered phenobarbital and paraldehyde, which were the treatments for status epilepticus until the 1960s. During the 1950s, clinical research established the pediatric dosage of parenteral phenytoin for the treatment of seizures, which was based on the adult dosage adjusted to each child's weight. Studies in the late 1970s and early 1980s established more appropriate dosing for neonates and children on a milligram-per-kilogram basis. Scientifically derived dosing guidelines have been available only for the past 12 years. Side effects associated with parenteral phenytoin, caused primarily by its high pH level and the propylene glycol content needed to increase its solubility, were frequently reported during the 1970s and 1980s, after 25 years of clinical use. Intravenous administration of phenytoin caused burning at the infusion site and was associated with severe local cutaneous reactions following infiltration into surrounding tissue, leading to a recommendation that intravenous phenytoin be avoided in young children and the elderly. The propylene glycol solvent was linked to seizures, arrhythmia, asystole, and hepatic and renal damage. When administered intramuscularly, phenytoin is poorly absorbed and can cause hemorrhagic necrosis of the soft tissues at the injection site. Many of these side effects can be avoided in children with the use of fosphenytoin. (J Child Neurol 1998; 13(Suppl 1):S11-S14).
Clinical Experience With Fosphenytoin in Children
Authors: Morton Lawrence Daniel
Published: September 2009

Fosphenytoin, a phenytoin prodrug, can be administered in a variety of intravenous diluents and has a more neutral pH value than phenytoin. The pharmacokinetics, safety, and tolerability of fosphenytoin in children from 1 day to 16 years old have been evaluated in two multicenter studies. Data are available from 78 patients who received loading doses (62 with intravenous administration and 16 with intramuscular administration). In these studies, fosphenytoin was converted to phenytoin within 8.3 minutes (range, 2.5-18.5 minutes). In addition, no significant difference in conversion rates was noted from the youngest to the oldest patient. No deaths or serious, alarming, or unexpected adverse events occurred; most adverse events were consistent with those seen with phenytoin therapy in adults. Both intravenous and intramuscular administration were well tolerated, with mild bruising, tenderness, swelling, and/or erythema seen at infusion and injection sites in a small number of patients. (J Child Neurol 1998;13(Suppl 1):S19-S22).
Does A View of Nature Promote Relief From Acute Pain?
Authors: Kline Grace A.
Published: September 2009

Inadequate control of acute pain is a well-recognized and serious problem. Distraction is one of the methods used in adjunct with medications to relieve pain. Nature-related sensory stimuli are frequently used for both distraction and relaxation. The human response model that focuses on individual adaptation to health conditions is used in this article to guide an analysis of relevant studies. Four studies in clinical settings evaluated the effect of nature (as a visual stimulus) to determine whether it promoted relief of acute pain. All these studies also used audio stimuli (nature sounds or music). Distracting visual and auditory stimuli used together provided stronger evidence of pain reduction than when either type of stimulus was used alone.
Adverse effects associated with arginine α-ketoglutarate containing supplements
Authors: Prosser JM , Majlesi N. , Chan GM , Olsen D. , Hoffman RS , Nelson LS
Published: September 2009

The athletic performance supplement industry is a multibillion-dollar business and one popular category claims to increase nitric oxide (NO) production. We report three patients presenting to the emergency department with adverse effects. A 33-year-old man presented with palpitations, dizziness, vomiting, and syncope, after the use of NO2 platinum. His examination and electrocardiogram (ECG) were normal. The dizziness persisted, requiring admission overnight. A 21-year-old man with palpitations and near syncope had used a "nitric oxide" supplement. He was tachycardic to 115 bpm with otherwise normal examination. Laboratory values including methemoglobin, and ECG were unremarkable. He was treated with 1 L of saline with no change in heart rate. He was admitted for observation. A 24-year-old man presented after taking NO-Xplode with palpitations and a headache. His examination, laboratory values, and ECG were normal. He was discharged. The purported active ingredient in these products is arginine α-ketoglutarate (AAKG), which is claimed to increase NO production by supplying the precursor L-arginine. The symptoms could be due to vasodilation from increased levels of NO, though other etiologies cannot be excluded. AAKG containing supplements may be associated with adverse effects requiring hospital admission.
Cross-sectional study on respiratory effect of toner-exposed work in manufacturing plants, Japan: pulmonary function, blood cells, and biochemical markers
Authors: Kitamura H. , Terunuma N. , Kurosaki S. , Hata K. , Ide R. , Kuga H. , Kakiuchi N. , Masuda M. , Totsuzaki T. , Osato A. , Uchino B. , Kitahara K. , Iwasaki A. , Yoshizumi K. , Morimoto Y. , Kasai H. , Murase T. , Higashi T.
Published: September 2009

The aim of the study is to examine the relationship between toner-exposed work and health indices related to respiratory disorders and to confirm the baseline of a cohort study to clarify the effect of toner exposure in manufacturing plants. Subjects were 1614 male workers (809 toner-exposed workers and 805 referents) who were engaged in toner manufacturing plants in Japan (Fuji Xerox Co., Ltd). The age of subjects was from 19 to 59 years, and the average age was 40.2 years(median 40 years, SD 7.67). We conducted a pulmonary function test (PEFR, VC, FVC, FEV1.0%, V25/Ht) and a blood cell test (RBC, Hb, Hct, Plt, WBC, cell contents of WBC) and measured biochemical indices in blood (ALT, AST, γ-GTP, CRP, IgE) and 8-hydroxy-2’-deoxyguanosine (8-OHdG) in urine. Student t-test and logistic regression analysis were applied to compare between the toner-exposed workers and the referents and to analyze the relationship among indices of effects and independent factors. There was no significant difference between the two groups in blood cell count and biochemical indices. Inflammation- and allergy-related markers such as 8OHdG and IgE also showed no significant difference between toner-exposed workers and the referents. The influence of smoking on pulmonary function indices was observed, but there was no relationship between the pulmonary function and toner-exposed work. In this article, we report a preliminary cross-sectional analysis in the subjects of a cohort study. No difference in pulmonary function indices was observed between the toner-exposed workers and the referents, and there was no consistent relationship between the exposure status and examined indices; however, the prevalence of subjective respiratory symptoms was higher in the exposed workers as presented in another report. Further analysis is important in the ongoing cohort study to clarify the effect of toner exposure on respiratory systems.
Development of a highly controlled gas-phase nanoparticle generator for inhalation exposure studies
Authors: Miettinen M. , Riikonen J. , Tapper U. , Backman U. , Joutsensaari J. , Auvinen A. , Lehto VP , Jokiniemi J.
Published: September 2009

We have developed a gas-phase nanoparticle generator that produces stable and well-defined size distributions for TiO2. The online analyses of the gas-phase compounds and total number concentration of the generated particles as well as the off-line analysis of the filter samples confirmed the stability of the production. The major advantage of this reactor is that the test substance is directly in the aerosol phase, and thus no preprocessing is needed. This eliminates the physicochemical changes between bulk and administrated material during storing or processing. This system is easy to adjust to different experimental setups and precursors. As a result, well-characterized nanomaterials for inhalation exposure studies can be produced. At mass concentration of 30 mg/Nm3, the count mean diameter was 126 nm (geometric SD 1.6), mass mean diameter was 161 nm (2.0), mass median aerodynamic diameter was 125 nm, and the concentrations of harmful gas-phase by-products remained low. The produced powder consisted of crystals of anatase (77 vol%) and brookite (23 vol%), and its specific surface area was 69 m2/g.
Risk assessment model of occupational exposure to nanomaterials
Authors: Giacobbe F. , Monica L. , Geraci D.
Published: September 2009

Recent development of nanotechnology allows precise assessment of the risks workers are exposed to. To assess the risks, a specific risk assessment model has been developed with reference to workplaces where nanoparticles are present. This model allows identification and quantification of the health hazards for workers. The use of nanomaterials presents some uncertainties regarding effective level of danger, and risk assessment takes this into consideration with the help of an appropriate index. An evaluation algorithm considers both normal work conditions and abnormal/emergency situations. Evaluation outcome consists of several risk levels with several subdivisions. For each single level, it is possible to develop specific behavioral guidelines. The present evaluation model has been implemented in research laboratories. The results are middle to high-level risks.
Experimental evaluation of personal protection devices against graphite nanoaerosols: fibrous filter media, masks, protective clothing, and gloves
Authors: Golanski L. , Guiot A. , Rouillon F. , Pocachard J. , Tardif F.
Published: September 2009

In this study, different conventional personal protection devices (fibrous filters, cartridges for respirators, protective clothing, and gloves) well qualified for micron particles were tested with graphite nanoparticles ranging from 10 to 100 nm (electrical mobility diameter). For this purpose, two specific test benches were designed: one for filter-based devices which are tested under a controlled air flow and other for gloves and protective clothing based on the “through diffusion method.” The penetration versus particle size shows for most tested filter media the behavior predicted by the theoretical Brownian capture: penetration decreases when particle diameter decreases. No thermal rebound was detected until 10 nm for graphite nanoparticles. Protective clothes were tested by two methods and same trends were obtained. Nonwoven fabrics (air-tight materials) are much more efficient against nanoparticles than cotton and paper. Gloves tested by “through diffusion technique,” in static condition seem to efficiently protect against graphite nanoparticles in spite of their important porosity.
A nanobiological approach to nanotoxicology
Authors: Nyland JF , Silbergeld EK
Published: September 2009

There is an urgent need to develop efficient and rapid strategies in order to characterize the potential health risks associated with nanomaterials, given the speed with which applications and uses are increasing. Use of standard toxicity methods will not be sufficient to meet this need. This article proposes the adoption of two novel guidances: the system’s biological approach to toxicity testing advocated by the US National Research Council and a nanobiological perspective that identifies key events at the nanoscale that are relevant to signal transduction and structural biology.
Acute endosulfan poisoning: a retrospective study
Authors: Jeong Mi Moon  , Byeong Jo Chun
Published: September 2009

Endosulfan is a widely used insecticide that is associated with a high fatality rate in humans when ingested accidentally or with the aim of suicide. However, the literature concerning human endosulfan exposure is limited to case reports. Thus, we sought to 1) describe the clinical features of patients with acute endosulfan poisoning and 2) identify independent factors to predict patients’ outcome. Fifty-two patients who presented with acute endosulfan poisoning between January 2001 and January 2007 were enrolled in this retrospective study. Sixteen (30.7%) of the 52 patients died, and 48 patients experienced seizures. Endosulfan poisoning caused the hypotension and the abnormalities on electrocardiogram at presentation. Over half of the patients developed complications, such as rhabdomyolysis, hepatic toxicity, and hypotension. These complications resolved without sequelae in the survival group. Refractory status epilepticus was the most common cause of death in this series (75.0%). Amount ingested being greater than 35 g of endosulfan was the most found to be an independent variable that predicted patient mortality. Patients with this risk factor must be treated aggressively during the early stage of endosulfan poisoning.
Lipoprotein (a) Levels in Childhood Arterial Ischemic Stroke
Authors: Teber Serap , Deda Gülhis , Akar Nejat , Soylu Kazım
Published: September 2009

Lipoprotein (a) is a cholesterol-rich plasma lipoprotein with a lipid composition similar to that of low-density lipoproteins (LDL). Many prospective and case-control studies identified elevated levels of lipoprotein (a) as a risk factor for premature myocardial infarction and stroke. Elevated lipoprotein (a) has been identified as a genetically determined risk factor for stroke in young adults, but only preliminary data are available on its role as a risk factor for ischemic stroke in infants and children.

Fifty two children with arterial ischemic stroke and 78 age- and sex-matched healthy children were studied. Data of this study indicate that 26.9% of children with arterial ischemic stroke had high lipoprotein (a) levels in comparison with the age matched healthy control group.

Measurement of lipoprotein (a) should be included in screening programs performed in young patients suffering not only from venous thromboembolism but also arterial ischemic stroke, in addition to other thrombophilic factors.
Final Report On the Safety Assessment of Sodium Lauraminopropionate and Sodium Lauriminodipropionate
Authors: Andersen F. Alan
Published: September 2009

Sodium Lauraminopropionate and Sodium Lauriminodipropionate are used in a variety of cosmetic formulations as antistatic agents, hair conditioning agents, and surfactants. Current data on concentrations at which these ingredients appear in cosmetic formulations were unavailable. The oral LD50 for Sodium Lauraminopropionate in albino rats was reported to be 8 g/kg. Evidence from limited studies in rabbits suggests that Sodium Lauraminopropionate and Sodium Lauriminodipropionate are both dermal and ocular irritants. No evidence of sensitization was found in guinea pigs with either ingredient. No data were available on the teratogenic, mutagenic, or carcinogenic potential of these ingredients, nor was there any clinical test data available. Because of the lack of data, the safety of Sodium Lauraminopropionate and Sodium Lauriminodipropionate could not be substantiated. The data needed to make a safety assessment include the method of manufacture, chemical characterization (i.e., data on purity / impurities), chemical and physical properties of Sodium Lauraminopropionate, concentration of use in cosmetic formulations, 28-day dermal toxicity, dermal reproductive and developmental toxicity, any available ocular irritation data (no new studies should be undertaken to provide this data), dermal irritation and sensitization at concentration of use, and two different genotoxicity studies (one using a mammalian system). If the latter data are positive, dermal carcinogenesis data using the methods of the National Toxicology Program will be needed. It cannot be concluded the these ingredients are safe for use in cosmetic products until these safety data have been obtained and evaluated.
Final Report On the Safety Assessment of Benzoxiquine1
Authors: Andersen F. Alan
Published: September 2009

Benzoxiquine is described as a biocide for use in cosmetic products. It is currently reported to be used in only one product. In a separate finding, the Food and Drug Administration determined that Benzoxiquine is not generally recognized as safe and effective in over-the-counter topical antifungal drug products. The only data available on the toxicity of Benzoxiquine indicates that it is mutagenic in the Ames test without metabolic activation. Because of the lack of data, the safety of Benzoxiquine could not be substantiated. The data needed to make a safety assessment include purity/impurities, ultraviolet absorption (if there is absorption, then photosensitization data will be needed), 28-day dermal toxicity, dermal teratogenicity, ocular irritation (if already available only), dermal irritation and sensitization, and two different genotoxicity studies (one using a mammalian system). If the latter data are positive, dermal carcinogenesis data using the methods of the National Toxicology Program will be needed. It cannot be concluded that Benzoxiquine is safe for use in cosmetic products until these safety data have been obtained and evaluated.
Influence of Origin or Controlled Feeding On Longevity of Sprague-Dawley Rats
Authors: Knight E.V. , Barrett D.S. , Keenan C.M. , Kimball J.P. , Eitzen B.H. , Bryant S. , Smith L.N. , Szot R.J. , Powers W.J.
Published: September 2009

Two-year studies were undertaken in Sprague-Dawley (SD) rats to assess the effects of origin, group housing, or various feeding regimens on longevity. This report describes results of in-life findings pertaining to body weight gain, food consumption, palpable masses, and preliminary analysis of clinical pathology parameters and necropsy observations. The first study compared ad libitum feeding of SD rats from the following suppliers: Charles River Labs (CRL) International Standard (IS) and Original Standard (OS), Ace Animals, Inc., and Harlan Sprague-Dawley, Inc. The second study assessed individual and group housed ad libitum feeding of Purina Certified Rodent Chow 5002 (20% crude protein), and individually housed controlled feeding of either Purina 5002 or Opti-diet (14% crude protein). The in-life phase of the third study has recently been completed. This study compared controlled (5.5 g Purina 5002 biscuit) to ad libitum (Purina 5002) feeding in CRL IS rats. In the supplier study, survival of male rats was markedly greater for CRL (IS) rats when compared to other groups. Body weight gain and food consumption were greatest in the CRL (OS) rats. Increases in cholesterol, triglycerides, urea nitrogen, and gross renal disease were observed in Harlan and Ace SD rats, while CRL rats had a higher incidence of grossly detectable pituitary masses and foci. In the feeding study, controlled feeding significantly increased the survival rate and decreased body weight gain. Single and group housed SD rats fed ad libitum had decreased T4 and markedly higher cholesterol and triglyceride values, when compared to rats fed controlled diets. Survival of IS rats fed a controlled diet was also notably higher than ad libitum-fed IS rats in the third study.
National Toxicology Program Experience With Dietary Restriction: Does the Manner in Which Reduced Body Weight Is Achieved Affect Tumor Incidence?
Authors: Haseman Joseph K.
Published: September 2009

The increasing body weights and the associated increased tumor incidences observed in recent long-term rodent bioassays may adversely affect study sensitivity for detecting rodent carcinogenicity. For example, increasing body weights may result in reduced survival and fewer animals at risk for tumor development. Moreover, the increased control tumor incidences observed in the more recent studies make it more difficult to establish firm baseline values and to use historical control data in the overall evaluation of experimental results. Finally, if dosed animals are significantly lighter than controls within a given study, then it may be more difficult to detect carcinogenic effects for those tumor sites sensitive to body weight changes. One approach to deal with this problem is food restriction, and the recently completed NTP Dietary Restriction Study confirmed that reducing food intake can reduce background tumor rates in control animals. There was also a slight increase in survival (approximately 2 wk on average) in the food restricted animals. However, the experimental protocol that restricted food consumption in both dosed and control groups appeared to have reduced sensitivity for detecting carcinogenic effects relative to the standard NTP protocol. One important, but often overlooked, issue when considering dietary restriction is that tumor incidence profiles may differ for animals of equivalent body weight, depending upon how the reduced body weights were achieved. An evaluation of data from NTP long-term rodent studies and from the NTP Dietary Restriction Study indicates that food restricted animals show a significant reduction in a number of site-specific tumors relative to equivalently sized ad libitum-fed animals. These results suggest that a dietary restriction strategy that focuses on achieving similar body weights in dosed and control groups may produce false positive outcomes if substantially more food restriction is required for control groups than for dosed animals (e.g., if control animals must receive a moderate (15—20%) degree of food restriction to achieve body weights equivalent to those observed in ad libitum-fed dosed animals). Results from the NTP Dietary Restriction Study also demonstrate that a moderate (15—20%) food restriction protocol applied equally to dosed and control animals may produce false negative outcomes if the resulting body weights are substantially different in dosed and control groups. Alternative strategies for reducing body weights are briefly discussed, but at present it is unclear which strategy or combination of strategies will ultimately prove to be most effective for dealing with the problem of increasing body weights.
Amended Final Report On the Safety Assessment of Dioctyl Sodium Sulfosuccinate
Authors: Andersen F. Alan
Published: September 2009

Dioctyl Sodium Sulfosuccinate is an anionic surfactant used in a wide variety of cosmetic formulations. In September 1994, the Cosmetic Ingredient Review (CIR) Expert Panel evaluated the ingredient to be safe up to 0.42% in cosmetic formulations. Since that time, CIR received a petition to re-open the safety assessment based on new clinical data. This amendment is a compilation of data contained in the original plus the data received in the petition; the latter appear at the end of this document. Studies conducted in the 1940's indicate that the oral LD50 in rats can be as low as 1.9 g/kg. Short-term subchronic and chronic animal studies of the same vintage found little toxicity at levels around 1% of the LD50 level. Inhalation studies likewise had few findings. Dioctyl Sodium Sulfosuccinate was minimally irritating to intact animal skin, but moderate to severely irritating to abraded skin. A concentration of 25% was a severe ocular irritant, but 10% produced little or no irritation. Mutagenesis tests were negative. A repeated insult patch test (RIPT) in 110 individuals produced no sensitization at a concentration of 5%. Erythema was noted during induction in a number of subjects at concentrations ≤5%. The CIR Expert Panel recognized that surfactants such as Dioctyl Sodium Sulfosuccinate would likely produce irritation under the conditions of a RIPT. The Panel cautioned that as the ingredient is a cumulative irritant, care should be taken to avoid irritancy in formulations intended for prolonged contact with the skin. The Panel concluded that Dioctyl Sodium Sulfosuccinate is safe for use in cosmetics.
Final Report On the Safety Assessment of Mink Oil
Authors: Nair Bindu
Published: September 2009

Mink Oil is obtained from the subdermal fatty tissues of the mink. The oil is a mixture of the natural glycerides of 14-20 carbon chain fatty acids. Mink Oil is used in cosmetic formulations as a hair conditioning agent, an occlusive skin conditioning agent, and as a surfactant. Current data on concentration of use is limited. A Mink Oil cream was noncomedogenic in rabbits following repeated (5 days a week for 2 weeks) applications, although minimal hyperemia and hyperplasia were noted at the treated site toward the end of the treatment. No sensitization was observed in animals treated with Mink Oil under occlusive patches, but sensitization was seen in animals treated with intradermal injections of Mink Oil in a maximization procedure. Mink Oil was not an ocular irritant in animals. Clinical studies done under occlusive patches found no irritation. In another clinical test, a rinse-off product containing 2.8% Mink Oil was applied to the skin for five consecutive days without rinsing. Some erythema was noticed, but in a repeat of the test, no erythema was seen. Mink Oil is reported to provide a minimal sun protection factor (SPF), but did not appear to increase the SPF when added to a solution containing recognized sunscreens. Studies using human volunteers indicate that Mink Oil applied to the skin remains on the skin surface. Additional safety test data are needed, including a 28-day dermal toxicity study, ultraviolet (UV) absorption data (and if the ingredient absorbs in the UVA or UVB region, then photosensitization data are also needed), and method of manufacture (extraction). Independent of these data needs, it is concluded that the total polychlorinated biphenyl (PCB)/pesticide contamination should not exceed 40 ppm with not more than 10 ppm for any specific residue. Because there are additional data needed in order to complete the safety assessment, the overall conclusion is that the available data are insufficient to support the safety of Mink Oil for use in cosmetic products.
Final Report on the Safety Assessment of Ceteth-1, -2, -3, -4, -5, -6, -10, -12, -14, -15, -16, -20, -24, -25, -30, and -45
Authors: Andersen F. Alan
Published: September 2009

The Ceteth family of ingredients are the polyethylene glycol (PEG) ethers of cetyl alcohol. They are manufactured by the ethoxylation of cetyl alcohol with the number of moles of ethylene oxide corresponding to the average polyethylene glycol chain length desired. Not all of the polymer chain lengths covered in this assessment are currently reported to be used, but all are listed as cosmetic ingredients and may have been used in the past and could be used in the future. Ceteths are surfactants used as emulsifying, cleansing, and solubilizing agents in cosmetic formulations. Limited safety test data are available on ingredients in the Ceteth family, all consistent with surfactant properties. In separate studies, 2.5% Ceteth-2 was irritating to abraded skin, but 3.0 % was not irritating to intact skin. Dose-dependent irritation was noted for Ceteth-2 and Ceteth-10 at concentrations ranging from 5% to 100%. Ceteth-20 was found to enhance transposition of a marker from phage λ to bacterial DNA. Toxicity data, including reproductive and developmental toxicity, carcinogenesis data, and clinical testing data, available from previous safety assessments on Polyethylene Glycol and Cetyl Alcohol, were summarized. Although PEGs were mild irritants/sensitizers, there was evidence of nephrotoxicity in burn patients exposed to PEGs, and no such effects were seen in animal studies on intact skin. This led to a recommendation that PEGs not be used on damaged skin. Irritant effects of Ceteths on abraded skin not seen with intact skin likewise suggested that cosmetic manufacturers should not use Ceteths in products that may be used on damaged skin. Although metabolites of ethylene glycol monalkyl ethers are reproductive and developmental toxins, it was considered unlikely that the relevant metabolites would be found in or produced from the use of Ceteths in cosmetic formulations. Of concern was the possible presence of 1,4-dioxane and ethylene oxide impurities. The importance of using the necessary purification procedures to remove these impurities was stressed. Inhalation of Cetyl Alcohol at 26 ppm for 6 hours caused mucosal irritation, but shorter exposures at a concentration of 9.6 mg/L caused no irritation. Based on this data and with particle size and cosmetic use concentrations, Ceteths were considered to be safe for aerosolized use. Based in part on the limited data available on Ceteths included in the report and on the previous reviews of the two components found in Ceteths, it was concluded that Ceteth-1, -2, -3, -4, -5, -6, -10, -12, -14, -15, -16, -20, -24, -25, -30, and -45 are safe in the present practices of use.
Final Report on the Safety Assessment of Cocamide MEA
Authors: Andersen F. Alan
Published: September 2009

Cocamide MEA is a mixture of ethanolamines of fatty acids derived from coconut oil. This cosmetic ingredient functions as a surfactant—foam booster and an aqueous viscosity-increasing agent. To supplement the available data on Cocamide MEA, data from previous safety assessments of Coconut Oil and its derivatives, Monoethanolamine (MEA), and Cocamide DEA (Diethanolamine) were included in this safety assessment. These data suggest little acute, short-term, or chronic toxicity associated with dermal application. MEA vapor, however, is highly toxic. Although DEA is readily nitrosated to form N-nitrosodiethanolamine, a known animal carcinogen, MEA has not been found to form a stable nitrosamine. Dermal application of Cocamide MEA at concentrations of 50% was nonirritating to mildly irritating in animal tests. For comparison, Cocamide DEA at a concentration of 30% was a moderate irritant; Coconut Oil was nonsensitizing; and MEA was irritating and corrosive. Cocamide MEA was negative in the Ames Test. Cocamide DEA was positive in some mutagenesis assays, but negative in others. In clinical tests, Cocamide MEA at a concentration of 50% was not irritating in a single-insult patch test. Cocamide DEA at 2% in formulation caused irritation, but not sensitization. Predictive patch tests with a surfactant containing Cocamide DEA at 10% produced no adverse effects. Inhalation of MEA by humans is toxic. Based on the limited data available data on Cocamide MEA, and on the data on those ingredients previously reviewed, particularly Cocamide DEA, it was concluded that Cocamide MEA is safe as used in rinse-off products and safe at concentrations up to 10% in leave-on products. It was further concluded, however, that Cocamide MEA should not be used as an ingredient in cosmetic products in which N-nitroso compounds are formed or in formulations that will be aerosolized.
Special Report: Reproductive and Developmental Toxicity of Ethylene Glycol and Its Ethers
Authors: Andersen F. Alan
Published: September 2009

Polymers of Ethylene Glycol are linked via ether linkages with various alcohols or via ester linkages to various fatty acids in many cosmetic ingredients. Ethylene Glycol, when reacted with an alkyl alcohol, forms an ethylene glycol monoalkyl ether. These compounds are metabolized in the human body by alcohol dehydrogenase and aldehyde dehydrogenase to form corresponding acetaldehyde and acetic acid derivatives. Data are presented that show reproductive and developmental toxicity is associated with metabolites of ethylene glycol monoalkyl ethers, but not with the monoalkyl ethers themselves. Further, it is suggested that the toxicity of these metabolites is inversely proportional to the length of the alkyl chain in the original alkyl ether. In the case of the compounds used in cosmetics, most have alcohols or fatty acids linked to polyethylene glycol chains, not a single Ethylene Glycol moiety. Where Ethylene Glycol is linked to a fatty acid by an ester linkage, the resulting compound is chemically different from the monoalkyl ethers. Where Ethylene Glycol is linked to an alcohol via an ether linkage, the alkyl chain is large and complex, suggesting little or no potential toxicity. Overall, it was found that metabolites of ethylene glycol monoalkyl ethers are reproductive and developmental toxins. In general, however, the metabolites of concern are not expected to be formed in cosmetic formulations that contain polymers of ethylene glycol.
Final Report on the Safety Assessment of PPG-9, -25, and -40 Diethylmonium Chloride
Authors: Andersen F. Alan
Published: September 2009

PPG-9, -25, and -40 Diethyhnonium Chloride are quaternary ammonium salts that function as antistatic agents in cosmetic formulations. Only PPG-9 and -25 Diethylmonium Chloride are reported to be used. Neither animal test data nor clinical test results were available. No data were provided in response to requests of interested parties to supply the needed data. Accordingly, the available data are insufficient to support the safety of these ingredients in cosmetics. The additional data needed include: (1) current concentration of use; (2) dermal absorption using PPG-9 Diethylmonium Chloride; if significantly absorbed, then a 28-day dermal toxicity study will be needed; (3) two genotoxicity assays, at least one in a mammalian system, of PPG-9 Diethyhnonium Chloride; if positive, then a 2-year dermal carcinogenicity study using NTP methods may be needed; (4) human skin sensitization and irritation at concentration of use; and (5) impurities data, especially nitrosamines. Depending on the findings in these studies, additional data such as reproductive and developmental toxicity may be needed.
Postnatal depression: A global public health perspective
Authors: Almond Palo
Published: September 2009

The aim of this paper is to discuss whether or not postnatal depression is a global public health concern. Public health is the study of the morbidity, mortality and the cause and course of disease, at a population rather than an individual level. Public health is also concerned with examining factors that cause health inequalities. Postnatal depression is a mental and emotional condition that can affect women during the first postnatal year. Since the effects of postnatal depression are known to go beyond the mother in that it also affects the partner and the child, it can be deemed a public health problem. Additionally, severe postnatal depression can lead to infanticide as well as maternal death, often by suicide. Furthermore, evidence demonstrates that all countries are faced with the challenge of postnatal depression, but low- to middle-income countries face the greatest burden. The literature revealed various treatment options for this complex condition. However, it also uncovered that not all women are assessed for postnatal depression, nor do all women receive treatment. The emerging picture is that postnatal depression is indeed a public health problem, particularly as the incidence is much higher than the quoted rate of 10%—15%. This paper recommends direction for public health-orientated perinatal mental health research and suggests that service providers should consider the routine assessment of all postnatal women.