Lecture 3 & 4: Hazard Ranking Score and Toxicity Continued Flashcards
What are the 3 categories of the HRS tool?
1) Likelihood of release
2) Waste characteristics
3) Targets of release
Describe the likelihood of release in the HRS tool
- Worst: release that has occurred
- Bad: release that is imminent (poor containment, overflow of containment, proximity to receptors)
- Bad: geology that promotes movement of release (slopes, proximity to groundwater or streams, soil types)
Describe waste characteristics
- Toxicity (based on reference doses)
- Persistence
- Mobility
- Bioaccumulation
- Present in lg volume
Describe the targets of release in the HRS tool
-who/ what is most likely to be impacted
- proximity to drinking water
- Proximity to human food chain
- Proximity to residents or workers
- Proximity to endangered species/ critical habitat
What are the pathways addressed on the HRS tool
1) ground water
2) surface water
3) Soil
4) air
How is the overall score measured in the HRS tool?
see equation on notes
What is the cutoff score for the HRS tool?
28.5
Describe how Europe differs from the U.S. in terms of toxicity testing
Test any chemicals that produced in more than 10 kg/yr. but don’t test on animals, have large database on chemical structures and health impacts
US: Do not need to test, only new chemicals or older chemicals that may cause harm
Give examples of acute toxicity
oxalic acid in spinach
alcohol
Give examples of chronic toxicity
lead exposure
drinking H2O with low concentration of trichloroeythylene
What organs break down toxic chemicals?
the liver and the kidneys
What are factors to consider in the LD50
- Dose administered, animal species (dioxin dose 5000x higher for hamsters than guinea pigs)
- Chemical metabolized differently in dif species
- how much is absorbed into the blood, stored in the liver and kidneys
What are the goals of toxicity testing?
- ID possible effects of exp to env agents
- Develop dose/response relationships, speak to sensitivity
- Predict effects of exposure in human population
What are the other purposes of toxicity testing (depending on the design)
- Evaluate general toxicity resulting from exposure of various duration
- Evaluate specific health effects, such as reproductive and developmental toxicity, neurotoxicity, immunotoxicity, genetic toxicity, carcinogenicity
What are the different types of toxicity testing?
- Actue testing
- Subchronic or repeated dose toxicity testing
- Chronic toxicity testing
Describe acute toxicity testing
- 24 hour period, 1 or a few doses
- obs time: days- 2 weeks
Observations: deviant behavior, growth, mortality
Test: LD 50
Describe subchronic or repeated dose toxicity testing
adverse effects of continuous of repeated exposure over a portion of average lifespan
time: usually 28 or 90 days
Obs time: 2 or 4 weeks
Observations: reversibility, persistence, delayed occurrence adverse effects
Method: 90-day study, 20 rodents per dose group
Goal: determine NOAEL- no observed adverse effect levels - guidelines for human exposure
Describe chronic toxicity testing
- Determine cumulative adverse effects of repeated daily exposure (oral, dermal, or inhalation) to dif doses for 12 months
- Need 2 animals: 1 rodent (rat) 1 nonrodent (dog)
- End: Gross necropsy and histopathological exam
How does toxicity testing usually progress when considering acute, subchronic, and chronic?
- starts with acute and progresses to subchronic and chronic
What other types of tests may the EPA require?
mutagenicity tests, carcinogenicity, reproductive, developmental
What United State Law addresses the screening of industrial chemicals?
Toxic Substances Control Act (TSCA) - 1976
Describe TSCA
- gives EPA authority to collect information and issue regulations on new and existing industrial chemical substances
- companies that manufacture of process new chemicals must submit a Public manufacturing notice (PMN)
What is a PMN?
includes information on chemical structure, production process, expected production volume, and other data concerning the chemical’s env or health effects known to or reasonably ascertainable by the chemical company
What are some issues with TSCA?
- **Does not detail a testing strategy to evaluate the large volume of existing or new chemicals
- **To register a new chemcial, companies are NOT required to conduct any specific toxicity tests and EPA estimates that only about 15% of PMNs contain health or safety data
Describe how the EPA has addressed some of the lack of data on existing chemicals
HPV chemical testing program- voluntary program created by the EPA
What is the purpose of the HPV chemical testing program?
ensures that basic toxicity data are available on all organic, nonpolymeric chemicals produced or used in the U.S. in excess of 1 million pounds per year
What tests are required by HPV chemical testing program? What is the battery of testing called?
SIDS: Screening Information Dataset
- Acute toxicity
- Repeated Dose toxicity
- Genetic toxicity in vitro (Point mutation and chromosomal aberration)
- Genetric toxicity in vivo
- Reproductive toxicity
- Developmental toxicity & teratogenicity
what happens if SIDS toxicity data are not available?
test plan proposed and reviewed by EPA and other organizations
Who was involved with the HPV Chemical testing program partnership?
EPA, American Chemical Council, American Petroleum Institute, and Environmental Defense
What are the two steps of the toxicity assessment?
- Hazard ID
* Dose-response evaluation
Describe hazard identification under the toxicity assessment
includes a description of the specific forms of toxicity (neurotoxicity, carcinogenicity, etc.) that can be caused by a chemical and an evaluation of the conditions under which these forms of toxicity might appear in exposed humans
How are data used in hazard ID typically derived?
from animal studies and other types of experimental work, but may come from epi studies
What is the dose-response evaluation
- more complex examination of conditions under which the toxic properties of a chemical might be evidenced in exposed people, with particular emphasis on the quantitative relationship between dose and toxic response
What is the dose-response relationship?
a type of graph used to describe the effect of exposure to a chemical or toxic substance upon an organism
*Need quantitative toxicity data, which comes from occupational, clinical, or epidemiological studies, or animal experiments
What is another name for a dose-response study
bioassay
How do acute dose response studies work?
- lab rats are fed a single dose of the chemical being tested
- exposure occurs only once but the response is measured after 14 days (to give time to react)
- at end, scientists count the dead rats in each dose group
- *Very high dose group: ?
- Very low dose group: ?
- *Medium dose ranges: ?
Describe LD50
Lethal dose 50
the dosage (mg of chemical/ kg body weight of the subject organism) causing death in 50 percent of exposed animals
The more toxic the compound the __ it’s LD50 value
lower
What is a threshold?
Draw an example of a no threshold dose-response curve
at or below the dose which effects do not occur and above which they do
See slide
Are there any criteria for establishing thresholds?
No
- may be biologically plausible for some endpoints, but the variation in response of sensitive members of the population makes it difficult to determine an absolute threshold for the entire population
How do we extrapolate dose response data?
- high dose to low dose
- animals to humans
Draw an example of alternative extrapolation models
See slide
How is data used in human health risk assessment?
- EPA published guidelines for using DR studies in RA, which cover specific endpoints:
- Developmental toxicity
- Reproductive toxicity
- Neurotoxicity
- non-cancer dose-response assessments
- Guidelines for carcinogens, providing detailed guidance on evaluating modes of action to id carcinogens and for conducting quantitative dose-response assessments
What are the primary models used for assessment of nonthreshold response? What contaminants are non threshold? Draw a graph.
- Carcinogens non threshold
- Models:
- one- hit model- assumes a single stage for cancer induced by 1 interaction (very conservative)
- Linear multi-stage- assumes multiple stages for cancer (Fits curve to experimental data)
- Multihit- least conservative- assumes several interactions needed before cell transformation
- Probit- assumes probit (lognormal) distribution for tolerances of exposed population (appropriate for acute toxicity, questionable for cancer)
What are slope factors? Draw the graph
See slide
Slope factor (SF)- carcinogen potency factor, dependent on route of exposure
Give an example of a slope factor
chloroform is a carcinogen with a slop factor (oral) of 6.1 * 10^-3
Draw a general dose response model for a non-cancerous chemical
See slide
