Suppression of the antibody response by a formamidine pesticide: Dependence on the route of exposure

Abstract

These studies investigated the effects of exposure to chlordimeform (CDM), a formamidine pesticide, on selected in vivo immune parameters in the random bred CD‐1 mouse. Further studies were done on the effects of this compound on the in vitro PFC response in C57BL/6 mice. Acute and 14‐d exposure to CDM via the i.p. route resulted in a decrease in IgM antibody‐forming (plaque‐forming) cells (PFC) directed at the sheep red blood cell (sRBC) antigen when measured 4 d after i.p. immunization. This suppression was seen at doses as low as 20 mg/kg·d for 14 d. These same doses of CDM did not result in any alteration of cell‐mediated immunity as measured by the delayed hypersensitivily response (DHR) to both keyhole limpet hemocyanin (KLH) and sRBC. Lymphocyte blastogenesis was increased in spleen cells from mice exposed to 40 mg/kg·d CDM in response to media alone, concanavalin A (Con A), and lipopolysaccharide (LPS). The in vitro PFC response by C57BL/6 mice was utilized to determine if CDM could suppress the antibody response due to a direct effect on the immune cells. CDM suppressed the in vitro PFC response only at concentrations that were directly cytolytic. A direct cytolytic effect was considered unlikely following exposure in the whole animal, since the suppression of the antibody response occurred in the absence of any effects on spleen cell number or spleen weight. To determine if route of exposure was a factor in the suppressive effects of CDM, 14‐d studies were conducted administering CDM orally at doses up to 120 mg/kg·d. Both the CD‐1 and C57BL/6 mouse were used to verify that a strain difference was not a factor. There was no effect on either the d 4 or d 5 antibody response, even though 43% of the mice exposed to 120 mg/kg died from the acute toxicity that can characterize this chemical. From an operational standpoint, these results indicate that the route of exposure of a compound relative to the route of administration of an antigen is an important consideration when determining the effects of that compound on an immune response. From an environmental standpoint, these results indicate that relatively high doses of chlordimeform do not result in consistent immunotoxicity as determined by the assays utilized.