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< > Literature Reports of CHEMICAL INACTIVATION for Prion Protein (associated with CWD of Deer and Elk):

OVERVIEW

Editorial Summary (Editorial Overview Text Replicated on Overall Chemical page - Prion Protein)

"Prions are inactivated by 1N NaOH, 4.0 M guanidinium hydrochloride or isocyanate, sodium hypochlorite (2% free chlorine concentration), and steam autoclaving at 132C for 4.5 h." (D131)

  • The abnormal prions associated with the transmissible spongiform encephalopathy (TSE) diseases are generally resistant to chemical inactivation. 
  • Sodium hypochlorite solution containing 20,000 ppm available chlorine is considered effective for inactivation of TSE agents.
  • Sodium hydroxide (1 M) is also considered effective, particularly in combination with gravity-displacement autoclaving.
  • Chemicals which have been shown to considerably, but not entirely, reduce infectivity, include the epoxide glycidol (GLD, 2,3-epoxy-1-propanol) at 3% or 5%, the detergent sarkosyl at high concentration and sodium dichloroisocyanurate solution containing the same level of available chlorine as sodium hypochlorite solution (20,000 ppm).
  • A variety of chemicals have been shown not to inactivate the TSE agents, including acetylethyleneimine, ethanol, ethylene oxide, chlorine dioxide, hydrogen peroxide, peracetic acid, phenolic disinfectants, potassium permanganate, urea, formalin/formaldehyde, B-propriolactone and ethylene oxide gas.
  • PrPres shows considerable resistance to degradation by proteases.
  • Purified scrapie prions have been shown to resist inactivation by chemicals which disrupt nucleic acids.

Chemicals causing inhibition of PrPres accumulation in vitro:

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Chemical treatments demonstrated to inactivate Prions

Editorial Summary
  • Sodium hypochlorite solution containing 20,000 ppm available chlorine is considered effective for inactivation of TSE agents.
Detailed Reports

Disinfectants containing chlorine

  • Two strains of mouse-passaged scrapie were completely inactivated by exposure to sodium hypochlorite containing 13,750ppm available chlorine for 30 minutes. Exposure to sodium hypochlorite solution containing 20,000ppm available chlorine for 60 minutes was suggested as an inactivating procedure. (J235.43S.w1)
  • Sodium hypochlorite solution containing 20,000 ppm available chlorine is effective for inactivation of TSE agents. (B297.6.w6); exposure for one hour was effective. (J235.43S.w1)
  • "Strong hypochlorite solutions achieve inactivation but other chlorine-releasing compounds are less effective."(J235.43S.w1)
  • Sodium dichloroisocyanurate solution containing the same level of available chlorine as sodium hypochlorite solution (20,000 ppm) were found to be less effective as they failed to release their available chlorine content. (B297.6.w6)
  • "2 M sodium hydroxide leads to substantial but incomplete inactivation." (J235.43S.w1)

  • Sodium hydroxide (1 M) for one hour, followed by gravity-displacement autoclaving at 121C for 30 minutes is considered to be effective; however there may be a problem with routine use of this combined procedure as the autoclave chamber may be affected by possible progressive degradative effects. (B297.6.w6)
  • OIE recommended disinfectants for BSE agent: "Sodium hypochlorite containing 2% available chlorine, or 2 N sodium hydroxide, applied for >1 hour at 20C, for surfaces, or overnight for equipment." (W31.29Mar03.w3)
    • "Recommended decontamination measures will reduce titres but may be incompletely effective if dealing with high titre material, when agent is protected within dried organic matter, or in tissue preserved in aldehyde fixatives." (W31.29Mar03.w3)

Detergents:

  • The detergent sodium dodecyl sulphate has been found effective against scrapie-infected tissue homogenates by boiling in 3% SDS for three minutes, but infectivity has been reported to survive following boiling (or autoclaving) of 50mg macerated brain samples for 15 minutes. It has been suggested therefore that hot SDS is useful only for inactivation of contaminated fluids. (J236.159.w1)
  • The detergent sarkosyl reduces titre of infectivity, but only at high concentrations of the detergent. (J236.159.w1)

Other chemicals:

  • Liquid ethylene oxide is effective for inactivation of prions, but ethylene oxide gas is ineffective. (J27.63.w1)
  • A solution of 2% sodium iodide for four hours produces only modest reduction in scrapie infectivity. (J236.159.w1). 

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Chemical treatments which have been shown to be ineffective for deactivation

Editorial Summary
  • The abnormal prions associated with the transmissible spongiform encephalopathy (TSE) diseases are generally resistant to chemical inactivation. 
  • A variety of chemicals have been shown not to inactivate the TSE agents, including acetylethyleneimine, ethanol, ethylene oxide, chlorine dioxide, hydrogen peroxide, peracetic acid, phenolic disinfectants, potassium permanganate, urea, formalin/formaldehyde, B-propriolactone and ethylene oxide gas.
  • PrPres shows considerable resistance to degradation by proteases.
  • Purified scrapie prions have been shown to resist inactivation by chemicals which disrupt nucleic acids.
Detailed Reports
  • Chemicals which have been shown to be ineffective for inactivation of TSE agents include acetylethyleneimine, ethanol, ethylene oxide, chlorine dioxide, hydrogen peroxide, peracetic acid, phenolic disinfectants, potassium permanganate and urea. (B297.6.w6)
  • Chemical disinfectants which do not have activity against prions include acids, alcohols, biguanides, phenolic compounds and quaternary ammonium compounds. Aldehydes, alkalis, chlorine, iodine and oxidising agents have some limited activity. (B21)
  • Chemical sterilisation using formalin, alcohol, urea (8 M), 2% peracetic acid, ethylene oxide (16 hours at 55C) are all "unsatisfactory"  for decontamination of items contaminated with scrapie agent. (B298.10.w10)
  • Partially sensitive to protease digestion. (J234.14.w1)
  • Resistant to inactivation by procedures that hydrolyse, modify or shear nucleic acids: (J20.160.w1)
    • No loss of infectivity following incubation for 24 hours at 65C with 2mM Zn2+ at pH 7.0 or 5mM Mg2+at pH 9.5. (In these conditions the divalent cations efficiently catalyse hydrolysis of RNA and, more slowly, DNA). (J20.160.w1)
    • Not inactivated by prolonged digestion with DNase I (two hours at 37C), RNase A and RNase T in combination for up to six hours or micrococcal nuclease (up to 43 hr at 37C). (J20.160.w1)
    • Resistant to psoralen photoadduct formation using high concentrations of psoralens (highly hydrophobic TMP (4,5',8-trimethylpsoralen), moderately hydrophilic HMT (4'-hydroxy-methyl-4,5',8-trimethylpsoralen) or very hydrophilic AMT (4'-aminoethyl-4,5',8-trimethylpsoralen) and black lamps with emission maximum 366 nm for time of up to 300 minutes). (J20.160.w1)
    • Resistant to hydroxylamine (NH2OH)at concentrations up to 1M. (J20.160.w1)
  • Glycidol (GLD, 2,3-epoxy-1-propanol), an epoxide, has been shown to reduce the infectivity of mouse-adapted scrapie strain Obihiro. Glycidol at 3% for five hours or at 5% for two, five or 12 hours at room temperature reduced infectivity by 102-103, as indicated by an increased incubation time in mice. The effect was increased at higher temperatures and in the presence of salt and in an alkaline environment. However infectivity was not completely removed, suggesting that a few portions of infectivity show considerable resistance to inactivation with glycidol; this may be associated with higher molecular weight oligomers of PrPSc. (J27.63.w1)
  • B-propriolactone at 5% for one hour at room temperature did not decrease PrPSc as indicated by the strength of a Western Blot signal using B-103 antibody. (J27.63.w1)
  • Propylene oxide only moderately decreased PrPSc as indicated by the strength of a Western Blot signal using B-103 antibody. (J27.63.w1)

Formalin:

  • Resistant to inactivation by formaldehyde. (J234.14.w1)
  • TSE agents survive formalin tissue fixation procedures. (B297.6.w6)
  • Scrapie survived 0.35% formalin for at least three months to produce disease in sheep inoculated with contaminated louping-ill vaccine. (B298.10.w10)
  • Using bioassay (intracerebral inoculation into goats) brain material which had been held in formalin for six, eight or 13 months still produced scrapie in inoculated goats within 20 months of inoculation and material which had been held in 12% formalin for 28 months produced disease in one of the two inoculated goats, the second still being healthy after 24 months. (J42.75.w2)

Nucleases:

  • Resistant to treatment by nuclease. (J234.14.w1)
  • Scrapie agent was shown to be resistant to treatment with ribonuclease or deoxyribonuclease, no increase in incubation period been seen in sheep inoculated with suspensions of scrapie-infected goat brain material following incubation with either enzyme for two hours. (J42.70.w1)

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Authors & Referees

Authors Dr Debra Bourne MA VetMB PhD MRCVS (V.w5)
Referee Suzanne I Boardman BVMS MRCVS (V.w6)

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