mutagenecity and carcinogenicity

Question 1

examples of in vitro screening tests

Answer 1

• mutagenic essays
• ames:salmonella/microsome assay
• micronucleus assay
• comet and sce
• dna adduct
  
  • dna methylation assays
    *

Question 2

examples of invivo tests

Answer 2

• rodent assays
  
  • 18 mnth exposure study in mice
  • more than 24 month exposure study in rats
• vmp n pesticides will not be licenced if they are positive on more than one essay
• many natural toxins are mutagenic and potential carcinonogens

Question 3

fungus that produce ochratoxin A

Answer 3

• aspergillus ochraceus
• aspergillus carbonarius
• penicillium verrucosum

Question 4

discuss the pathophysiology of OTA

Answer 4

• MOSTLY AFFECTS THE KIDNEY
• FOUND IN BALKAN AREA
• IT ALSO LEADS TO URINARY TRACT TUMORS
• PIGS AND HUMANS ARE THE ONES MOSTLY AFFECTED
• IT RESULTS IN FIBROTIC NON FUNCTIONAL KIDNEY WITH PU/PD

Question 5

CS OF OTA

Answer 5

• END STAGE RENAL DZ
• GLYCOSURIA
• PROTEINURIA
• INCREASED URINARY GGT CONC.
• PROGRESSIVE TUBULO-INTERSTITIAL NEPHROPATHY
• TUBULAR ATROPHY
• PERI-GLOBULAR FIBROSIS AND CORTICAL CYSTS
• UTT-URINARY TRACT TUMORS
  
  • POORLY CHARACTERISED RENAL AND UROTHELIAL TUMORS

Question 6

DISCUSS KINETICS OF OTA

Answer 6

• ORAL BIOAVAILABILITY APPROXIMATELY 66%
• PLASMA PROTEIN BINDING IS UP TO 99% (SPP DIFFERENCE)
• BLOOD SERUM CONC. IS A MARKER OF EXPOSURE
• IT LEAVES THE BODY RAPIDLY
• IT HAS LIMITED DISTRIBUTION BT HOWEVER IT HAS A AND B TRANSPORTERS, THEREFORE THERE IS ACTIVE TRANSPORT INTO KIDNEY AND MAMMARY GLANDS
• THEREFOERE OTA WILL BE FOUND IN MILK N KIDNEY
• CHILDREN WILL TAKE IT IF THEY ARE MILK FED

Question 7

INTERPRET THIS SLIDE

Answer 7

• THE TOP ONE HAS MOSTLY -VE RESULTS WITH FEW SPONTANEOUS MUTATION
  
  • THIS SALMONELLA DO NOT GROW IN ABSCENCE OF HISTAMINE
• WHEN U INCUBATE WITH MUTAGENIC COMPOUNDS THE SALMONELLA WILL GROW WITHOUT HISTAMIN
  
  • RECOGNISE THAT THE SALMONELLA GROW CLOSE TO THE MUTAGENIC COMPOUND IN THE MIDDLE
  • the once at periphery mutated spontaneously

Question 8

interpret this slide

Answer 8

• tocophenol is a vit e and it reduces/ blocks oxidative stress
• gluthathion (GSH) also deminishes oxidative stress

Question 9

primary target for OTA on kidneys

Answer 9

• PT (proximal tubule
• cause
  
  • karyomegaly
  • desquamation(skin peeling)
  • focal degeneration
  • focal peritubular fibrosis

Question 10

which farm animals are mostly affected by OTA

Answer 10

pigs and poultry

Question 11

mechanism of OTA toxicity in kidney

Answer 11

Toxicological testing indicated a specific renal toxicity,
driven by the accumulation of the compound in
proximal tubular cells followed by tubular injury

Question 12

a typical marker for OTA toxicity

Answer 12

karyomegally in Proximal tubular cells

Question 13

acceptable daily intake for OTA (ADI)/TWI/TDI

Answer 13

• 100ng/kg bw

Question 14

WHICH TEST DETERMINES NOAEL

Answer 14

90 DAY RODENT ASSAY

Question 15

WHAT IS THE BASIS FOR ADI

Answer 15

NOAEL

Question 16

WHAT PROVIDES THE BASIS FOR ACCEPTABLE RESIDUE LEVELS IN FOOD

Answer 16

ADI