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Chemwatch:4650.13 Page 13 of 18 Issue Date:11/12/2018 <br /> Version No:7.1.1.1 API Pond Ammonia Test Solution#1 Print Date:06121/2019 <br /> TOXICITY IRRITATION <br /> dermal(rat)LD50:>2000 mg/kg[11 Eye(rabbit):500mg/24h-mild. <br /> polyethylene glycol Oral(rat)LD50:600 mg/kg[21 Eye:no adverse effect observed(not irritating)['] <br /> Skin(rabbit):500mg/24h-mild. <br /> i <br /> Skin:no adverse effect observed(not irritating)['] <br /> SOD NITROPRUSSIDE TOXICI� IRRITATION <br /> SOLUTION Oral(rat)LD50:69.8 mg/kg[21 Not Available <br /> TOXICITY IRRITATION <br /> SODIUM SALICYLATE-USP Oral(rat)LD50:930 mg/kg[21 Eye:adverse effect observed(irritating)['] <br /> Skin:no adverse effect observed(not irritating)['] <br /> Legend: 1.Value obtained from Europe ECHA Registered Substances Acute toxicity 2.*Value obtained from manufacturer's SDS. <br /> Unless otherwise specified data extracted from RTECS-Register of Toxic Effect of chemical Substances <br /> for polyethylene glycols <br /> Pure polyethylene glycols have essentially similar toxicity,with toxicity being inverse to molecular weights.Absorption <br /> from the gastrointestinal tract decreases with increasing molecular weight <br /> The G.I.absorption of a series of polyethylene glycols has been studied.Polyethylene glycols having average molecular <br /> weights of 4000 and 6000 showed no absorption from the rat intestine over a five-hour period,while polyethylene glycols <br /> of 1000 and 1540 molecular weights showed a slight absorption amounting to less than 2%of the total dose during the <br /> same period.When 1 g doses of polyethylene glycols of molecular weight 1000(PEG 1000)and 6000(PEG 6000)were <br /> given intravenously to six human subjects,85%of PEG 1000 and 96%of PEG 6000 were excreted in the urine in 12 <br /> hours.When these two same materials in 10 g doses were given orally to five human subjects,none of the PEG 6000 <br /> was found in the urine in the following 24 hours,whereas about 8%of PEG 1000 administered was found to excrete in <br /> urine within 24 hours When PEG 400 was given intravenously to three human subjects,an average of 77%recovery of <br /> this material was found in the urine in 12 hours.However,when the same substance was given orally to the same three <br /> human subjects,a recovery of between 40 and 50%of the dose was determined in the urine in the course of the following <br /> 24 hours.Single oral doses of PEG 400 were incompletely recovered from urine and faeces of rabbits even when <br /> collection of excreta was continued as long as four days following the dose.Evidence from all these and other studies <br /> indicate that ethylene glycol is not formed as a metabolite of PEG 400 <br /> Prolonged skin contact of PEG 1500 and 4000 upon the skin of rabbits in dosages of 10 g/kg bw showed no deleterious <br /> effects on internal organs and little,if any,of the materials was absorbed through the skin. <br /> Although early reports indicated that skin sensitization was observed among a few human subjects and in guinea pigs <br /> tested with certain polyethylene glycols,later studies showed that currently produced materials were without irritating or <br /> sensitizing properties.However,recent report(Fischer,1978)demonstrated that four patients showed allergic reactions to <br /> lower molecular weight liquid polyethylene glycols in topical medications.Two had immediate urticarial reactions to PEG <br /> 400.Two other patients had delayed allergic eczematous reactions,one to PEG 200,and one to PEG 300. <br /> Polyethers,for example,ethoxylated surfactants and polyethylene glycols,are highly susceptible towards air oxidation as <br /> the ether oxygens will stabilize intermediary radicals involved.Investigations of a chemically well-defined alcohol <br /> POLYETHYLENE GLYCOL (pentaethylene glycol mono-n-dodecyl ether)ethoxylate,showed that polyethers form complex mixtures of oxidation <br /> products when exposed to air. <br /> Sensitization studies in guinea pigs revealed that the pure nonoxidized surfactant itself is nonsensitizing but that many of <br /> the investigated oxidation products are sensitizers.Two hydroperoxides were identified in the oxidation mixture,but only <br /> one(16-hydroperoxy-3,6,9,12,15-pentaoxaheptacosan-1-ol )was stable enough to be isolated.It was found to be a strong <br /> sensitizer in LLNA(local lymph node assay for detection of sensitization capacity).The formation of other hydroperoxides <br /> was indicated by the detection of their corresponding aldehydes in the oxidation mixture. <br /> On the basis of the lower irritancy,nonionic surfactants are often preferred to ionic surfactants in topical products. <br /> However, <br /> their susceptibility towards autoxidation also increases the irritation.Because of their irritating effect,it is difficult <br /> to diagnose ACD to these compounds by patch testing. <br /> Allergic Contact Dermatitis—Formation,Structural Requirements,and Reactivity of Skin Sensitizers. <br /> Ann-Therese Karlberg et al;Chem.Res.Toxicol.2008,21,53-69 <br /> Polyethylene glycols(PEGs)have a wide variety of PEG-derived mixtures due to their readily linkable terminal primary <br /> hydroxyl groups in combination with many possible compounds and complexes such as ethers,fatty acids,castor oils, <br /> amines,propylene glycols,among other derivatives.PEGs and their derivatives are broadly utilized in cosmetic products <br /> as surfactants,emulsifiers,cleansing agents,humectants,and skin conditioners. <br /> PEGs and PEG derivatives were generally regulated as safe for use in cosmetics,with the conditions that impurities and <br /> by-products,such as ethylene oxides and 1,4-dioxane,which are known carcinogenic materials,should be removed before <br /> they are mixed in cosmetic formulations. <br /> Most PEGs are commonly available commercially as mixtures of different oligomer sizes in broadly-or narrowly-defined <br /> molecular weight(MW)ranges.For instance,PEG-10,000 typically designates a mixture of PEG molecules(n=195 to <br /> 265)having an average MW of 10,000.PEG is also known as polyethylene oxide(PEO)or polyoxyethylene(POE),with <br /> the three names being chemical synonyms.However,PEGs mainly refer to oligomers and polymers with molecular <br /> masses below 20,000 g/mol,while PEOs are polymers with molecular masses above 20,000 g/mol,and POEs are <br /> polymers of any molecular mass.Relatively small molecular weight PEGs are produced by the chemical reaction between <br /> Continued... <br />