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Health Consequence Scoring for Chemical Contaminants in Animal Feed

Health Consequence Scoring for Chemical Contaminants in Animal Feed

Karen Ekelman, Ph.D. 
AFSS Public Meeting
September 12, 2006

Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 1

Slide 2

Outline

  • Review and Background
  • Health Consequence Scoring for Chemical Feed Contaminants
    • Acute Adverse Effects
      • Severity Scores
      • Potency Scores
      • Examples
    • Chronic Adverse Effects
      • Severity Scores
      • Potency Scores
      • Examples
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 2

Slide 3

Review: AFSS Relative Risk Model

  • Goal: The AFSS Relative Risk Model is a tool for ranking relative risks of feed contaminants to aid FDA in setting priorities for allocating its resources in a risk-based manner
  • Relative Risk Score = Health Consequence Score (HCS) x Exposure Score (ES)
  • Health Consequence Score (HCS) = Severity Score (SS) x Potency Score (PS)
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 3

Slide 4

Review: AFSS Relative Risk Model

  • Reminders:
    • The list of potentially harmful feed contaminants should not be considered to be the definitive list of feed contaminants that pose a significant risk to animal or human health
      • Some items on the list may turn out to pose very low relative risks to animal or human health
      • Some items may need to be added to the list
    • Health Consequence Scores for contaminants are not Relative Risk Scores (Exposure is missing)
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 4

Slide 5

Review: AFSS Relative Risk Model

  • Health Consequence Scores (HCS) for chemical and biological contaminants will be developed for:
    • Appropriate species:
      • Food-producing animals such as cattle, swine and chickens
      • Pets such as dogs and cats
      • Humans
    • Specific exposure scenarios:
      • Acute and chronic exposures for chemicals
      • Acute exposures for biological contaminants
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 5

Slide 6

Chemicals: Acute Adverse Effects

Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 6

Slide 7

Chemicals: Acute Adverse Effects

  • Acute adverse effects occur following a single or short-term exposure to a toxic dose of a chemical
    • Acute adverse effects may be:
      • Easily identified by trained or untrained observers (death, seizures, vomiting), or
      • Identified only after laboratory examination of affected tissues and organs
    • Acute adverse effects may occur
      • Immediately after exposure, or
      • Be delayed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 7

Slide 8

  • Chemicals: Acute Adverse Effects
    • Data on acute adverse effects come from:
      • Results of accidental or deliberate poisonings in humans and animals (anecdotal reports)
      • Data from acute toxicity tests conducted on animals
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 8

Slide 9

Chemicals: Acute Adverse Effects

  • Most acute toxicity test data on chemicals come from the LD50 test (LD = Lethal Dose)
    • LD50 is the amount of a chemical given in a single dose that causes the death of 50% of a group of test animals; can be measured or extrapolated
    • Most are conducted in rodents, so results need to be extrapolated to other species
    • Oral LD50 results are most relevant
    • LD50 is usually measured in mg of the chemical per kilogram of body weight of the test animal
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 9

Slide 10

Chemicals: Acute Adverse Effects

  • Acute Health Consequence Score =
    • Acute Severity Score x Acute Potency Score
  • Acute Severity Scoring
    • The Acute Severity Scores for chemicals are numerical scores assigned to a chemical based on the types of effects observed in relevant acute toxicity studies or data from other sources
    • The Acute Severity Score for a chemical is based on the most severe (worst) effect observed in all studies used to assess the acute toxicity of the chemical
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 10

Slide 11

Chemicals: Acute Adverse Effects

Severity Scoring for Acute Adverse Effects

AcuteaAcute Adverse Effects
1No adverse effects
2Adverse effects other than those listed below
3Neurological or neurobehavioral adverse effects
10Death
a Weighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 11

Slide 12

Chemicals: Acute Adverse Effects

  • Acute Health Consequence Score =
    • Acute Severity Score x Acute Potency Score
  • Acute Potency Scoring
    • Acute Potency Scores are numerical scores assigned to a chemical based on the measured or extrapolated doses that killed 50% of the test animals after administration of a single dose of the chemical (e.g. the LD50 value)
    • For chemicals with more than one reported LD50 value, the lowest value is used to determine the Acute Potency Score for the chemical
    • Acute Potency Scores may need to be adjusted for known species differences in sensitivity to a chemical
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 12

Slide 13

Chemicals: Acute Adverse Effects

Acute Chemical Potency Scores are assigned based on three 1/LD50 ranges:

ScoresRanges: 1/LD50 Values
1Lowest 1/LD50 values (lowest potency)
3Mid-range 1/LD50 values
10Highest 1/LD50 values (highest potency)
a Weighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 13

Slide 14

Chemicals: Acute Adverse Effects

  • Acute Potency Scoring (cont.)
    • To incorporate information from acute toxicity studies other than LD50 reports, a weight-of-the-evidence approach will be used to assign the study results to the appropriate potency category, using:
      • Information for chemicals with related chemical and physical properties
      • Information for chemicals with similar toxicity profiles
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 14

Slide 15

Example: Health Consequence Scores for Acute Adverse Effects of 16 Chemical Contaminants

Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 15

Slide 16

Example: Severity Scoring for Acute Adverse Effects

ScoresaAcute Adverse Effects
1No adverse effects
2Adverse effects other than those listed below
3Neurological or neurobehavioral adverse effects
10Death
a Weighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 16

Slide 17

Example: Potency Scoring for Acute Adverse Effects

ScoresaRanges: 1/LD50 Values (& no. of chemicals per range)
10.0002 – 0.0083 (4 chemicals)
30.00113 – 0.00441 (6 chemicals)
100.0122 – 0.2 (6 chemicals)
a Weighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 17

Slide 18

Acute HCS: 16 Chemicals

Health Consequence Scoring (HCS) for Acute Adverse Effects

ChemicalSSLD501/LD50PSSS x PS = HCS
Lindane10760.013210100
Aflatoxin B11050.2110
Chlorpyrifos10820.0122110
Carbaryl102300.0043330
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 18

Slide 19

Acute HCS: 16 Chemicals

Health Consequence Scoring (HCS) for Acute Adverse Effects

ChemicalSSLD501/LD50PSSS x PS = HCS
Malathion108850.00113330
Iprodione1035002.86E-4110
Diazinon103000.0033330
Methoxychlor1050000.0002110
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 19

Slide 20

Acute HCS: 16 Chemicals

Health Consequence Scoring (HCS) for Acute Adverse Effects

ChemicalSSLD501/LD50PSSS x PS = HCS
Dicofol105750.00174330
Lead1012008.33E-4110
Ethoxyquin108000.00125330
Fumonisin B1 & B21027303.66E-4110
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 20

Slide 21

Health Consequence Scoring (HCS) for Acute Adverse Effects

ChemicalSSLD501/LD50PSSS x PS = HCS
Dieldrin10380.026310100
Ethion10270.037010100
Imazilil102270.00441330
Aldrin10390.02561100
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 21

Slide 22

Example: Ranking of 16 Chemicals by Acute Health Consequence Scores (HCS)

HCSChemicals
10Lead, Fumonisin B1 & B2, Iprodione, Methoxychlor, Aflatoxin B1, Chlorpyrifos
30Imazilil, Dicofol, Ethoxyquin, Malathion, Diazinon, Carbaryl
100Aldrin, Ethion, Dieldrin, Lindane
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 22

Slide 23

Chemicals: Chronic Adverse Effects

Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 23

Slide 24

Chemicals: Chronic Adverse Effects

  • Chronic toxicity occurs when a toxic dose of a chemical is consumed for a significant portion of the subject’s lifetime
  • Chronic toxicity data can come from:
    • Long-term studies in humans (epidemiological studies)
    • Long-term studies in laboratory animals
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 24

Slide 25

Chemicals: Chronic Adverse Effects

  • The following set of studies is usually used to determine the chronic toxicity of a chemical:
    • Chronic toxicity studies
    • Carcinogenicity studies
    • Reproductive toxicity studies
    • Developmental toxicity studies
  • Fewer or shorter studies on a chemical result in greater uncertainty in estimating its chronic toxicity
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 25

Slide 26

Chemicals: Chronic Adverse Effects

  • Chronic Health Consequence Score =
    • Chronic Severity Score x Chronic Potency Score
  • Chronic Severity Scoring
    • The Chronic Severity Score is a numerical score assigned to a chemical based on the types of effects observed in chronic toxicity studies or from other data sources
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 26

Slide 27

Chemicals: Chronic Adverse Effects

Chronic Severity ScoresaChronic Adverse Effects
1No adverse effects
2Adverse effects other than those listed below
3Neurological or neurobehavioral adverse effects
4Reproductive or developmental adverse effects w/o maternal toxicity
5Cancer
10Death
a Weighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 27

Slide 28

Chemicals: Chronic Adverse Effects

  • Chronic Health Consequence Score =
    • Chronic Severity Score x Chronic Potency Score
  • Chronic Potency Scoring for effects other than cancer
    • A Chronic Potency Score is assigned to a chemical based on the most severe (worst) effect observed in all studies used to assess the chronic toxicity of the chemical
    • Basis for the Chronic Potency Score is an estimate of an Acceptable Exposure Level (AEL) for each chemical contaminant
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 28

Slide 29

Chemicals: Chronic Adverse Effects

  • The AEL (Acceptable Exposure Level) is an estimate of the amount of a chemical that can be ingested daily over a lifetime without an appreciable risk of adverse effects
    • AEL is analogous to EPA’s reference dose (RfD) and FDA’s Acceptable Daily Intake (ADI)
    • The AEL is usually expressed on a body weight basis (e.g., mg/kg body weight/day)
    • AEL is determined according to standard methods for deriving RfDs and ADIs
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 29

Slide 30

Chemicals: Chronic Adverse Effects

  • To calculate an AEL (Acceptable Exposure Level):
    • Determine the NOEL (No Observed Effect Level) or NOAEL (No Observed Adverse Effect Level) for each study used to determine the chronic toxicity of the chemical
    • Divide each NOEL or NOAEL by appropriate safety factors (SF); this number is an AEL
    • The lowest AEL calculated from studies used to determine the chronic toxicity of a chemical is the AEL assigned to the chemical
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 30

Slide 31

Chemicals: Chronic Adverse Effects

Safety Factors

FactorsaPurpose
10Intra-species variability
10Sub-chronic to chronic
10Severity of effects (developmental and reproductive only)
10Inter-species extrapolation
a Other factors can be used, especially if they were used by federal regulatory agencies or other authoritative scientific bodies in their evaluations of the subject chemical
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 31

Slide 32

Chemicals: Chronic Adverse Effects

  • The Chronic Potency Score for non-cancer endpoints is determined by placing the inverse of the AELs (1/AEL) for all chemical contaminants on a comparative scale
    • Scale in then divided into 3 categories
    • Each category is assigned a Chronic Potency Score
  • Acute Potency Scores may need to be adjusted for known species differences in sensitivity to a chemical
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 32

Slide 33

Chemicals: Chronic Adverse Effects

Chronic Potency ScoresRanges: 1/AEL
1Lowest 1/AELs (least potent)
3Mid-range 1/AELs
10Highest 1/AELs (most potent)
aWeighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 33

Slide 34

Chemicals: Chronic Effects

  • Chronic Potency Scoring for cancer effects
    • One measure of carcinogenic potency is the estimated dose associated with a one in one million lifetime risk of cancer (Lifetime Cancer Risk)
      • For cancer-causing chemicals with estimated one in one million lifetime risk doses, those estimates will be used to determine the Chronic Potency Score using a scale similar to the one established for the non-cancer chronic effects
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 34

Slide 35

Chemicals: Chronic Adverse Effects

Chronic Potency Scores for CancerRanges: 1/LCR Doses (1/Lifetime Cancer Risk Doses)
1Low 1/LCR doses (least potent)
3Mid-range 1/LCR doses
10High 1/LCR doses (most potent)
aWeighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 35

Slide 36

Chemicals: Chronic Adverse Effects

  • Chronic Potency Scoring for cancer effects (cont.)
    • For cancer-causing chemicals without estimates of a one in one million risk dose, a weight-of-the-evidence approach will be used to assign the chemical to the appropriate potency category, based on
      • Analyses by various regulatory bodies
      • Information on chemicals with related chemical, physical or toxicological properties
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 36

Slide 37

Example: Health Consequence Scores for Chronic, Non-Cancer Adverse Effects of 14 Pesticides

Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 37

Slide 38

Example: Severity Scoring

Chronic Severity ScoresaChronic Adverse Effects
1No adverse effects
2Adverse effects other than those listed below
3Neurological or neurobehavioral adverse effects
4Reproductive or developmental adverse effects w/o maternal toxicity
5Cancer
10Death
aWeighting of scores can be changed
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 38

Slide 39

Example: Potency Scoring

 

a Weighting of scores can be changed 

Chronic Potency Scores1/AEL Ranges (& no. of pesticides in range)
110 – 208 (7 pesticides)
31000 -- 2000 (4 pesticides)
105000 – 20000 (3 pesticides)
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 39

Slide 40

Example: 14 Pesticides (1)

Health Consequence Scoring (HCS) for Chronic Adverse Effects

PesticideSSAEL1/AELPSSS x PS = HCS
Iprodione20.0254012 x 1 = 2
Lindane30.0048120813 x 1 = 3
Malathion440.0234314 x 1 = 4
Pirimiphos-methyl440.00520014 x 1 = 4
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 40

Slide 41

Example: 14 Pesticides (2)

Health Consequence Scoring (HCS) for Chronic Adverse Effects

PesticideSSAEL1/AELPSSS x PS = HCS
Methoxychlor40.0110014 x 1 = 4
Carbaryl40.0005200034 x 3 = 12
Chlorpyrifos40.000110000104 x 10 = 40
Aldrin50.0005200035 x 3 = 15
Diazinon20.0002500032 x 3 = 6
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 41

Slide 42

Example: 14 Pesticides (3) Health Consequence Scoring (HCS) for Chronic Adverse Effects

PesticideSSAEL1/AELPSSS x PS = HCS
Dieldrin40.0000520000104 x 10 = 40
Ethion40.0005200034 x 3 = 12
Imazilil20.01258012 x 1 = 2
Carboxin100.110110 x 1 = 10
Chlordane100.00052000310 x 3 = 30
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 42

Slide 43

Example: Ranking of 14 Pesticides by Chronic, Non-Cancer Health Consequence Scores (HCS)

HCSPesticides
2Imazilil, Iprodione
3Lindane
4Methoxychlor, Malathion, Pyrimiphos-methyl
6Diazinon
10Carboxin
12Ethion, Carbaryl
15Aldrin
30Chlordane
40Dieldrin, Chlorpyrifos
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 43

Slide 44

Chemical and Physical Contaminants: Summary

  • Health Consequence Score (HCS) x Exposure Score (ES) = Relative Risk Score
  • HCS = Severity Score x Potency Score
    • SS = Severity Score
      • Acute Effects SS for Chemicals
      • Chronic Effects SS for Chemicals
    • PS = Potency Score
      • Acute Effects PS for Chemicals
      • Chronic Effects PS for Chemicals
  • Need to develop a weighting scheme for Acute HCS, Non-cancer Chronic HCS and Cancer HSC scores
Health Consequence Scoring for Chemical Contaminants in Animal Feed - Slide 44