How Does Haz-Map Handle Information from
Animal Toxicology and Medical Toxicology?
For occupational
cancers, Haz-Map follows IARC in the way it synthesizes animal and
epidemiological data. For acute occupational diseases, animal data is
sufficient if the routes of entry correspond. Examples of such acute
occupational diseases include poisoning by pesticides, solvents,
simple asphyxiation, hydrofluoric acid, and toxic pneumonitis.
In Haz-Map, there is a
distinction between adverse effects (includes animal toxicology and
human poisonings by ingestion cases) and occupational diseases (cases
of workers made ill after inhalation or skin absorption). Thus, for
six conditions in Haz-Map (hepatotoxicity, methemoglobinemia, peripheral
neuropathy, hemolytic anemia, chemical asphyxiation, and aplastic
anemia) each chemical is linked to either the adverse effect, the
adverse effect and the disease, or neither. For example, hydrogen
cyanide causes chemical asphyxiation in both animal experiments and
workplace accidents. Hydrogen cyanide is linked to both the adverse
effect and the disease. Copper is a reported cause of hemolytic anemia
after ingestion (linked to adverse effect) but not after occupational
exposure (not linked to occupational disease).
“Serious limitations
of toxicologic studies include differences between species and routes
of exposure. For example, gavage (tube feeding) differs greatly from
the routes by which patients typically have been exposed. In addition,
animal studies almost invariably depend on use of relatively high
doses of single toxins, and invariably require extrapolation to be
applicable to clinical situation.” [Rosenstock, p. 40]
“Animal cancer tests,
which are done at the maximum tolerated dose (MTD), are being
misinterpreted to mean that low doses of synthetic chemicals and
industrial pollutants are relevant to human cancer. About half of the
chemicals tested, whether synthetic or natural, are carcinogenic to
rodents at these high doses. A plausible explanation for the high
frequency of positive results is that testing at the MTD frequently
can cause chronic cell killing and consequent cell replacement, a risk
factor for cancer that can be limited to high doses. Ignoring this
greatly exaggerates risks.” [Ames
BN, 1998, PMID 9677052]