The effects of diisopropylmethylphosphonate, a by-product of the production of sarin and a contaminant in drinking water at the Rocky Mountain Arsenal, on female mink.

Abstract

This paper challenges the interpretation of the report on the effects of DIMP on mink with respect to mortality causation and organ-specific toxicity (i.e., liver, kidney, and thymus). During the second generation (F(1)) of a two generation toxicity study by on the effects of DIMP on female brown Ranch Wild mink, a cluster of six premature deaths occurred, being attributed to an unintentional anesthetic overdose that induced a stress-related syndrome rather than DIMP exposure. The present paper reveals that the six adult female mink (i.e., four DIMP treated and two controls) had medical conditions that pre-existed the administration of anesthetic. Three of the four DIMP-exposed mink that died displayed evidence of medically significant red blood cell damage and immune system involvement, while all six mink had elevated blood serum enzymes (ALT/AST) indicative of liver damage along with confirmatory histopathology indicating severe liver damage. These findings challenge the conclusion of Bucci et al. that the six mink deaths were solely caused by stress induced by anesthesia, and suggest DIMP related pre-existing conditions (e.g., red blood cell damage and elevated ALT/AST) may have contributed to the deaths in DIMP-treated mink. also inexplicably combined both the pregnant and non-pregnant animal data, thereby precluding an assessment of the effects of DIMP on pregnant and non-pregnant mink. A re-evaluation of the findings of the data revealed that pregnancy/lactation significantly influenced the incidence of physiologic alterations and histological lesions in the female mink for the kidney, liver, and thymus, findings that were masked by the combining of pregnant and non-pregnant results. Further evaluations indicated that DIMP treatment also significantly induced liver lesions in pregnant mink and kidney lesions in both pregnant and non-pregnant mink. These findings challenge the conclusions of Bucci et al. concerning the effects of DIMP on mink as well as identify for the first time that pregnancy/lactation in mink is a risk factor in the induction of thymic atrophy and the elevation of serum ALT/AST.

• Authors: Edward J Calabrese
• Journal: Regulatory toxicology and pharmacology : RTP (Regul Toxicol Pharmacol) Vol. 37 Issue 2 Pg. 191-201 (Apr 2003) ISSN: 0273-2300 [Print] Netherlands
• PMID: 12726753 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Organophosphorus Compounds
• Water Pollutants
• diisopropyl methylphosphonate
• Sarin

Topics

• Animals
• Colorado
• Female
• Food Contamination (statistics & numerical data)
• Liver (drug effects, metabolism, pathology)
• Mink
• Organophosphorus Compounds (metabolism, toxicity)
• Pregnancy
• Sarin (metabolism, toxicity)
• Water Pollutants (metabolism, toxicity)