Re-evaluation of Drinking-Water Guidelines for Diisopropyl Methylphosphonate (2000) / Chapter Skim
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Evaluation
Evaluation
Pages 5-26
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From page 5... ...
(1979) , four groups of 24 female and 6 male dark variety mink were administered feed containing DIMP at concentrations of 0, 50, 150, and 450 parts per million (ppm)
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From page 6... ...
No treatment-related effects were observed with regard to body weight, feed consumption, hematocrit values, hemoglobin parameters, and leukocyte counts, nor were any effects observed on reproduction. Gross and histologic examinations of the test animals showed no consistent changes, and there was no significant difference in organ weight compared with controls.
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From page 7... ...
consisted of three groups of 35 female and 7 male Ranch Wild mink fed DIMP in their diet at concentrations of 150, 450, and 2500 ppm. Two replicate control groups were fed untreated feed.
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9 · - ~ o 5 o bC o i= of Ct s~ .
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From page 10... ...
was more than adequate to evaluate any potential reproductive issues. Toxicity was assessed using standard parameters of periodic body weight, food consumption, and clinical examination.
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From page 11... ...
The subcommittee notes that several types of medical interventions were performed on the mink, including subcutaneous injections of lactated Ringer's solution to prevent dehydration in wasting animals, addition of palatable foods to the mink ration to encourage feeding, the occasional use of antibiotics, and treatment with phosphoric acid for '~et bellf' (urinary incontinence and skin inflammation)
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From page 12... ...
Hematologic and clinical chemistry changes were observed in the Fo and Fat generations. In the Fo generation, decreases in red-blood-cell count and increases in reticulocyte numbers, mean cell volume, and Heinz body counts (protein aggregates in oxidatively stressed red blood celIs)
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From page 13... ...
These findings were attributed to the shortened life span of Heinz-body-containing red blood cells, because the spleen removes damaged red blood ceils from circulation and is involved in the production of replacement red blood cells. No similar changes were found in the Fat generation, but an increase in mean ovarian follicle count was reported.
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From page 14... ...
When compared with pairfed controls, there was no significant difference in body weight. However, significant weight loss in male and female mink fed DIMP at 1136 mg/kg-day could be explained only partially by the use of pair-fed contro!
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From page 15... ...
Two groups of eight adult Ranch Wild mink of each sex were administered DIMP by Savage at doses of 27 or 170 mg/kg. A third group of mink was treated with the lower dose intravenously.
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are shown. No standard errors or standard deviations were provided.
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Again the absence of standard error data makes comparisons difficult. In the urinary elimination study, male rats excreted a larger percentage of the dose in the urine than did females.
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From page 18... ...
Although this general conclusion is qualitatively supported by the data, some sex-related and species-related differences deserve comment. Female mink eliminate DIMP slightly slower than do males, as noted with the blood time course of total radioactivity and with the urinary elimination profiles.
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From page 19... ...
If this is the case, the two phases in urinary excretion represent initial metabolic clearance of DIMP from a central compartment by metabolism and then redistribution of DIMP to the central compartment from deep tissue stores, which in this case would most likely be fat. Comparison of the four groups indicates that the deep storage sites are largest in female rats, followed in order by male rats, female mink, and male mink.
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From page 20... ...
Mink are known to suffer from nursing disease. In this syndrome, dams unable to meet the heavy metabolic requirement of milk production late in lactation die from the negative nutritional balance (Schneider and Hunter 1993~.
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Another difference between mink and rodents or dogs is the mink's TABLE 2 Several Biologic Parameters of Mink, Rats, and Dogs Mink Rat Dog Body weight, kilograms 1-1.5 0.5 10 Age at maturity, months 8-12 3 6+ Life span, years 6-11 3 12-18 First litter, months 8-12 2 6-12
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From page 23... ...
1980~. Three studies in mink were conducted after EPA and Colorado made their determinations to assess whether the increase in female mink mortality in the Aulerich et al.
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2The exposure duration in these studies were 90-days in the dog study, 30 weeks in the three-generation rat study, and 10 days in the rat teratogenicity study.
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25 Ct ·_ · ~4 ._ sit ~ _ ~ Ct C=., o ~ o ec en o a)
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26 ·~ en at: Ed ·o Ct o _ be 8 · ~ CD to to to 11 E 1 by oo o o 22 UD V, o .
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