title: Two-generation reproductive study in mink fed diisopropyl methylphosphonate (DIMP).
abstract: Two generations of "Ranch Wild" mink (Mustela vison) were fed the organophosphate diisopropyl methylphosphonate (DIMP) at 0, 150, 450, or 1250ppm, to determine potential toxicity to the dams. Chemical, hematologic, necropsy, and microscopic examinations were performed on all parental animals and representative kits. The F0 and F1 dams had 3.4 and 4.6% mortality, respectively, distributed among all groups and not attributed to DIMP exposure. Adverse effects were mild and limited to the highest dose group. Plasma cholinesterase was reduced 40% (F0) and 31% (F1), as was whole blood cholinesterase (16 and 8.5%). Heinz bodies were present in 2.8% (F0) and 1.3% (F1) of erythrocytes. The erythrocyte count was reduced 6.3% in the F0. Reproductive efficiency was not affected. The mink were not uniquely susceptible to DIMP, relative to the literature on other species. The no observed adverse effect level (NOAEL), based on the 450ppm group of F1 females, was 56.5mg DIMP/kgBW per day; the lowest observed adverse effect level (LOAEL) was 329.5mg DIMP/kgBW per day.
authors.affiliation: Pathology Associates International, Frederick, MD 21701, USA. tbucci@nctr.fda.gov
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Bucci
authors.forename: Robert M
authors.initials: RM
authors.lastname: Kovatch
authors.forename: Michael D
authors.initials: MD
authors.lastname: Mercieca
authors.forename: Victor
authors.initials: V
authors.lastname: Perman
authors.forename: J S
authors.initials: JS
authors.lastname: Klingensmith
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002802:Cholinesterases / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006366:Heinz Bodies / Q000378:metabolism; D008297:Male; D008907:Mink / Q000097:blood / Q000254:growth & development / Q000502:physiology*; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects / Q000502:physiology*; D013154:Spleen / Q000187:drug effects / Q000254:growth & development; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D009943:Organophosphorus Compounds; D014874:Water Pollutants, Chemical; C023477:diisopropyl methylphosphonate; D002802:Cholinesterases