Substantial amounts of animal and human toxicity data have
never been systematically reviewed to identify chemicals
with the potential to adversely effect human health. This
is particularly true for health effects like neurotoxicity
or immunotoxicity that have not been the focus of
authoritative hazard identification efforts. After
compiling lists of suspected toxicants from the scientific and
regulatory literature (which often focus on the same small
set of well-studied toxicants), Environmental Defense initiated a research
project to supplement available hazard identification with
the results of a review of two large toxicological
databases: the National Institute for Occupational Safety
and Health's Registry of the Toxic Effects of Chemical
Substances (RTECS) database and the Carcinogenic Potency
database (CPDB).
Environmental Defense's lists of suspected toxicants from RTECS and CPDB
represent a screening-level evaluation of a chemical's
capacity to adversely effect human health. Chemicals listed
have been shown to cause target organ toxicity in either
humans or two mammalian species, by a relevant route of
exposure. This amount of evidence of reported adverse
health effects is sufficient to comprise a strong "hazard
signal" that warrants further action. Such action should
include compilation of an adequate screening information
dataset, a more comprehensive and authoritative evaluation
of whether the chemical could cause adverse effects in
humans, and appropriate exposure or risk reduction measures.
Environmental Defense adopted the hazard identification methodology developed
by researchers at the Oak Ridge National Laboratory to
identify suspected reproductive toxins. In their 1996 paper,
A Screening Method for Occupational Reproductive Health
Risk, Jankovic et al. compiled a list of reproductive toxins
by identifying chemicals from the RTECS database for which
adverse reproductive/developmental effects have been found
in humans or in at least two mammalian species tested via
the routes of exposure considered most relevant to humans
(i.e., inhalation, ingestion or dermal exposure). Using the
same criteria, Environmental Defense searched the RTECS and Carcinogenic
Potency databases to identify chemicals that exhibit
specific target organ toxicities.
To be identified as a suspected toxicant, a chemical must have undergone
relatively extensive toxicological testing and been reported
to exhibit adverse effects on the same organ system in at
least two mammalian laboratory species. Chemicals reported
to cause toxic effects in humans were also included on the
appropriate suspect list, whether or not these effects were
also documented in laboratory species.
DATABASE REFERENCES AND NOTES
CPDB: Carcinogenic Potency Database. Lawrence Berkeley Laboratory
Berkeley, CA.
http://potency.berkeley.edu/cpdb.html
The Carcinogenic Potency Database (CPDB) contains the results of
chronic, long-term animal cancer tests. Both qualitative and
quantitative information on positive and negative experiments are given,
including all bioassays from the National Cancer Institute/National
Toxicology Program (NCI/NTP) and results from the general literature
that meet a set of inclusion criteria. The database covers 5152
experiments on 1298 chemicals
Environmental Defense reviewed this compilation of results on carcinogenicity
in rats and mice and selected all chemicals with positive results in at
least two species by a relevant route of exposure. Chemicals that met
these screening criteria and that had not already been
authoritatively identified as recognized carcinogens under Proposition
65 were added to the Scorecard's list of suspected carcinogens.
RTECS: Registry of Toxic Effects of Chemical Substances. National
Institute for Occupational Safety and Health, Cincinnati, OH.
http://www.cdc.gov/niosh/rtecs.html RTECS is available through various vendors. Environmental Defense utilized Chem-Bank CD-ROM (August 1997).
The Occupational Safety and Health Act requires NIOSH to list "all known
toxic substances...and the concentrations at which... toxicity is known
to occur". To fulfill this mandate, NIOSH has been compiling a database
since 1971 that now contains records on over 130,000 chemicals. Six
types of toxicity data are included: (1) primary irritation; (2)
mutagenic effects; (3) reproductive effects; 94) tumorgenic effects; (5)
acute toxicity; and (6) other multiple dose toxicity.
Environmental Defense reviewed RTECS and abstracted all records of adverse
effects for the following Toxic Effects Codes:
Cardiovascular or Blood: G (cardiac), H (vascular), and
P(blood)
Endocrine: N (endocrine)
Gastrointestinal or Liver: K (gastrointestinal) and L
(liver)
Immunotoxicity: S (immunological including allergenic)
Kidney: M (kidney, ureter, bladder)
Musculoskeletal: Q (musculoskeletal)
Neurotoxicity: A (brain and coverings), B (spinal cord), C
(peripheral nerve and sensation), E (autonomic nervous
system), and F (behavior)
Respiratory: J (lung, thorax, or respiration)
Skin or Sense Organs: D (sense organs and special senses)
and R (skin and appendages)
These records were analyzed to select just those chemicals
with evidence of adverse impacts on an organ system that had
positive findings in humans or two different mammalian
species exposed by a relevant route of exposure. Chemicals
that met these screening criteria were added to the suspected
list for the relevant health effect.
HAZARD IDENTIFICATION METHOD REFERENCE
Jankovic, J. and F. Drake. A Screening Method for
Occupational Reproductive Health Risk. American Industrial
Hygiene Association Journal 57: 641-649. 1996.
