HEALTH EFFECTS|Environmental Defense's Project to Identify Suspected Health Hazards

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.

CPDB: Carcinogenic Potency Database. Lawrence Berkeley Laboratory Berkeley, CA.

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.
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.

Jankovic, J. and F. Drake. A Screening Method for Occupational Reproductive Health Risk. American Industrial Hygiene Association Journal 57: 641-649. 1996.