No. 1031 - Miljøstyrelsen

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10 CAS no Synonym Test Exposure route 556-67-2 D4 evaluation of D4 as inhibitor of human cytochrome P450 enzymes 556-67-2 D4 in vitro dermal absorption, Flow- Through Diffusion Cell System Species / model Conc. Exposure period in vitro human liver microsomes from 7 individuals in vitro percutaneous 556-67-2 D4 absorption potential oral gavage rat (♀,♂), Fisher 344 556-67-2 D4 physiologically based pharmacokinetic modelling (PBPK) 556-67-2 D4 physiologically based pharmacokinetic modelling (PBPK) human skin neat D4 and formulated D4 (antiperspirant) Result/Effects NOAEL / LOAEL 0.32 - 2.9 µM no data non competitive inhibitor of rat CYP2B1/2 (estimated Ki=0.11 mM) non competitive inhibitor of human CYP2B6 (estimated Ki=3.6 mM) competitive inhibitor of human CYP1A2 (estimated Ki=12 mM) non competitive inhibitor of human CYP2D6 and CYP3A4/5 (estimated Ki=14 and 11 mM) either competitive or non competitive inhibitor of CYP2C19 (estimated Ki=6.4 or 11 mM) little or no capacity to inhibit rat CYP1A2 and human CYP2A6, CYP2C9 and CYP4A9/11 activity activator of human CYP2E1 little or no capacity to to function as metabolism-dependent inhibitor of any of the P450 enzymes examined (except rat CYP1A1/2 and human CYP3A4/5 300 mg/kg 14C-D4 single exposure inhalation human 10 ppm 14C-D4 one hour during altering periods of rest and exercise inhalation, dermal, oral, i.v. 24 hours 0.50% of neat D4 absorbed (91.6% recovered from analysed sample) 0.49% of formulated D4 (103.2% recovered from analysed sample) carrier has an impact on absorption peak levels of radioactivity delayed relative to parent D4 by 24 hr most of the radioactivity in blood could be attributed to metabolites most of D4 absorbed from corn oil and neat D4 was metabolised and excreted via urine hepatic extraction calculated from model parameters was 0.65 to 0.8 (clearance nearly flow-limited) decreased retension of inhaled D4 during periods of exercise was explained by altered ventilation/perfusion characteristics and a rapid approach to steady-state conditions high lipophilicity coupled with high hepatic and exhalation clearance increased confidence in the utility of the model for predicting human tissue concentrations of D4 and metabolites during inhalation exposures rat no data no data pharmacokinetics of D4 delivered by inhalation or dermal routes is similar, and is different from the i.v. or oral delivery route EPA DCN/Ref. not relevant 86990000017 1998 not relevant 86980000163 1998 not relevant 86980000184 1998 not relevant Ready MB et al, 2003 not relevant Sarangapani R et al 2003
103 CAS no Synonym Test Exposure route 556-67-2 D4 pharmacokinetics inhalation via mouthpiece 556-67-2 D4 pharmacokinetics, PBPK modelling 556-67-2 D4 pharmacokinetics, pilot study 556-67-2 D4 percutaneous absorption, human skin / nude mouse model 556-67-2 D4 percutaneous absorption, 14C-D4, semi occlusive Species / model Conc. Exposure period human, 12 volunteers inhalation rat (♀,♂), Fisher 344 inhalation, nose only Result/Effects NOAEL / LOAEL 10 ppm one hour no changes in lung function rapid non-linear blood clearance mass transfer coefficient for D4 was 5.7×10-5 cm/s from lung air to blood 7, 70 and 700 ppm single exposure Despite its very high lipophilicity, D4 does not show prolonged retention because of high hepatic and exhalation clearance. rat (♂),Fisher 344 700 ppm, 14C-D4 6 hours radioactivity concentration highest in the lung tissue max. conc. of radioactivity in blood, plasma or tissues observed at end of exposure period rate of elimination of radioactivity from tissues the same as for plasma except for perirenal fat and lung elimination routes: expired volatiles, renal or faecal excretion percutaneous human skin neat and formulated D4 percutaneous rat (♀), Fisher-344 topical application at 10, 4.8, and 2 mg/cm 2 556-67-2 D4 immunotoxicity oral gavage rat (♀,♂), Fisher, 10 (♀,♂) / group 556-67-2 D4 non-regulated study; immunotoxicity 556-67-2 D4 immunotoxicity inhalation via mouthpiece 10, 30, 100, and 300 mg/kg EPA DCN/Ref. no data Utel MJ et al 1998 no data Andersen ME et al 2001 no data 86960000517 1996 24 hours absorption of neat D4 was determined to be 1.09% not relevant 86010000003 2000 1, 6 and 24 hours average percentage of applied dose being absorbed was between 0.57 and 0.95% for all doses and all time points significant decrease in per cent absorbed over time washing exposed skin after 24 hrs decreased exposure 28 days no alterations in NK cell activity, macrophage function, lymphocyte subpopulation no alterations in humoral activity (♂) dose-dependent increase in AFC-response (♀) slight but dose-dependent increase in erythroid elements (♀,♂) dose-dependent increase in liver weight and dose-dependent decrease in thymus weight (mostly ♀) systemic adsorption dependent on vehicle D4 at doses between 10 and 300 mg/kg does not cause immune suppression (♀,♂) oral human 12 mg two weeks no effects on studied immunological parameters or blood chemistry human 10 ppm one hour, reexposure after 3 months no immunotoxic or proinflammatory effects of respiratory exposure were observed not relevant 86010000009 2000 no data 86980000072 1997 no data 86990000015 1998 no data Looney RJ et al 1997
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Siloxanes - Consumption, Toxicity a
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Table of Contents PREFACE 5 SUMMARY
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Preface Siloxanes, the building blo
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8 products, clothes, health-care pr
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10 A possible estrogenic effect con
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Sammenfatning og konklusioner Denne
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Udledninger til miljøet Den væsen
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Prisen på alternativerne varierer
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1 Introduction 1.1 What are siloxan
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Cyclic siloxanes with other functio
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Curing of one-component RTV silicon
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Table 1.2 Consumption of silicones
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tion and export of siloxanes regist
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CAS No. Name Import average tonnes
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• Defoamers, flow control agents
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Besides their technical properties,
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paint, coatings and waxes in total
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Table 2.5 Siloxanes in imported, ex
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Fate of the siloxanes The siloxanes
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• Mouldmaking (reproduction of co
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The main source of releases of silo
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• Immunotoxicity studies. Human c
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LD 50 following dermal application
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cinogenic hazard associated with D5
Page 51 and 52: following repeated exposures, the l
Page 53 and 54: Table 4.1 PBT profiler results for
Page 55 and 56: 5 Alternatives The use of some type
Page 57 and 58: Name of alternative Neopentylglycol
Page 59 and 60: 5.1.7 Summary and general experienc
Page 61 and 62: Table 5.2 Identified alternatives t
Page 63 and 64: References Allan, R.B., Kochs, P. &
Page 65 and 66: EPA DCN 86970000024. 1996. Pharmaco
Page 67 and 68: EPA, August 2003. Siloxane D5 in Dr
Page 69 and 70: 69 Annex 1 Siloxanes listed in the
Page 71 and 72: 71 INCI name CAS No EINECS/ ELINCS
Page 79 and 80: Declared name CAS No. ACRYLATES / D
Page 81 and 82: Annex 3 Siloxanes in the Danish Pro
Page 83 and 84: Tonnes siloxanes Import Production
Page 89 and 90: tonnes siloxanes Import Production
Page 91 and 92: Annex 5 Siloxanes in cleaning and m
Page 93 and 94: tonnes siloxanes Import Production
Page 95 and 96: Annex 7 Database screening for deca
Page 97 and 98: Inhalation No relevant data found O
Page 99 and 100: PhysProp 2003. PHYSPROP DEMO-databa
Page 101: 10 CAS no Synonym Test Exposure rou
Page 105 and 106: 105 CAS no Synonym Test Exposure ro
Page 111: 111 CAS no Synonym 556-67-2, 541-02
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No. 1031 - Miljøstyrelsen

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