Kein Folientitel

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Update On Vinyl Acetate
Ursula Gundert-Remy Federal Institute for Risk
Assessment Bundesinstitut für Risikobewertung
(BfR) Berlin, Germany
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Risk Assessment of Vinyl Acetate performed in
the EU in the framework of EU Existing Chemicals
Programme
Risk Assessment of Vinyl acetat an intellectual
challenge
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Vinyl Acetate

• What is the current status?
• RAR Most parts of the risk assessment are
  finalised.
• Classification R20 agreed, R36/37
• What is new?
• Negative LLNA, new data no skin irritation
• Publication on Vinyl acetate induced
  intracellular acidification in mouse oral buccal
  epithelial cells (2005)
• Publication on Validation of Human
  Physiologically based pharmacokinetic model for
  Vinyl Acetate (2005)

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Vinyl Acetate
Acute toxicity

• oral LD50 3500 mg/kg
• dermal LD50 7440mg/kg
• inhaltion LC50 15 mg/L/hrs classification
  proposed R20 harmful by inhaltion

Irritation/ corrosivity

• proposed R36/37
• (irritating to eyes and to respiratory tract)
• new data delivered by industry
• which indicate no skin irritation

Sensitization

• LLN assay negativ
• no classification proposed

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Vinyl Acetate
no classification proposed
Repeated dose toxicity

• oral 90 day study
• NOAEL 684 mg/kg/day

• inhalation 2 years
• NOAEC local 50 ppm
• NOAEC systemic 50 ppm

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Vinyl Acetate
Reprotoxicity
no classification proposed
Fertility

• oral drinking water
• NOAEL 100 mg/kg/day

Developmental toxicity

• inhalation
• NOAEC 200 ppm (205 mg/kg/day)

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Vinyl Acetate
Genotoxicity
no classification proposed as mutagen
In vitro

• not mutagenic in bacteria
• positive findingschromaber, micronulei, SCE,
  DNA protein Xlinks

In vivo

• negativ DNA adducts rat liver
• positivmicronuclei in mouse bone marrow cells
  (toxic range), SCE rat bone marrow, sperm
  morphology in mice (toxic range)

Local genotoxicity??
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Vinyl Acetate
Carcinogenicity
Classification under discussion

• positive findings in rat nasal tumors
• NOAEC 50 ppm

Inhalation

• positive findings in rat and mouse
• LOAEL 5000 ppm (mouse) tumors in oral cavity,
  esophagus, stomach
• 10000 ppm (rat) tumors in oral cavity
• NOAEL lt 400 ppm

Oral route
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Vinyl Acetate conclusion

• I. Mode/Mechanism of action discussion still not
  finished
• Threshold vs Non-threshold?
• New findings
• Vinyl-acetate induced acidification
  demonstrated for buccal epithelial cells in a
  non-linear concentration dependent manner
• II. Interspecies extrapolation
• Extrapolation from the toxicokinetic animal
  nose model to the human model?
• New findings
• Validation of the human model by experimental
  data