Pathology considerations for, and subsequent risk assessment of, chemicals identified as immunosuppressive in routine toxicology.
Several proposals have been made with the aim of assisting in the early identification of chemicals with immunotoxic potential. The Organisation for Economic Cooperation and Development is now likely to incorporate enhanced immunopathology into the test guideline for the 28-day rat study, which may be regarded as a Tier I investigation. However, no guidelines have yet been proposed either for how the new data generated will be evaluated, or for how a subsequent risk assessment will be made. In this paper, considerations for the immunopathological assessment of the thymus, spleen, lymph nodes and bone marrow are described, together with comments on haematological and organ weight changes that may be associated with immunotoxicity. Their interpretation will depend on the doses at which changes are manifest, the quantity and quality of the effects observed and the presence and severity of other forms of toxicity. Lastly, risk assessment and the approach to Tier II testing in immunotoxicity is discussed. It is concluded that much of this work must be on a case-by-case basis, but should not in principle differ from the approach adopted for any other type of toxicity identified ina 28-day study.
Basketter
D A
DA
European Centre for Ecotoxicology and Toxicology of Chemicals, Brussels, Belgium.
Bremmer
J N
JN
Buckley
P
P
Kammuller
M E
ME
Kawabata
T
T
Kimber
I
I
Loveless
S E
SE
Magda
S
S
Stringer
D A
DA
Vohr
H W
HW
D000818:Animals; D001853:Bone Marrow / Q000187:drug effects* / Q000473:pathology; D005260:Female; D017408:Guidelines as Topic; D015386:Hazardous Substances / Q000008:administration & dosage / Q000633:toxicity; D007166:Immunosuppressive Agents / Q000633:toxicity*; D007391:International Cooperation; D008198:Lymph Nodes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D018570:Risk Assessment; D013154:Spleen / Q000187:drug effects* / Q000473:pathology; D013950:Thymus Gland / Q000187:drug effects* / Q000473:pathology
D015386:Hazardous Substances; D007166:Immunosuppressive Agents