Novel toxicity of tris(1,3‐dichloro‐2‐propyl) phosphate in adult male rats

Abstract

The widespread use of tris(1,3‐dichloro‐2‐propyl) phosphate (TDCIPP) as a flame retardant has led to its release to the environment. Thus, the toxicological effects of TDCIPP on humans and animals are of importance. For better understanding of its potential toxicities, TDCIPP (250, 500, or 650 mg/kg/day) or vehicle control was administrated orally to adult male Wistar‐Imamichi rats for 7 days. After the final administration of compounds, organ weights, histopathology, blood biochemistry, and hematology were examined. Hepatic toxicity was observed at doses ≥ 500 mg/kg/day of TDCIPP, and renal toxicity was observed at 650 mg/kg/day. The anti‐androgenic activity of TDCIPP was previously confirmed in vitro and in vivo, but weights of epididymis, an androgen‐dependent organ, were not affected by TDCIPP treatment in adults. Serum alkaline phosphatase activity was significantly decreased in all TDCIPP‐treated rats independent of dose. Hemoglobin concentration, hematocrit, red blood cell count, and reticulocyte count were decreased in all TDCIPP‐treated rats, but mean corpuscular volume, total iron‐binding capacity, and serum iron were normal, suggesting that renal anemia was caused by TDCIPP. Together with previous reports on effects of anti‐androgenic substances on red blood cell indices, anemia caused by TDCIPP could be due to its anti‐androgenic activity. These considerations will contribute to further assessment of the toxicity of the compound.

Toxicological effects of Tris (1,3‐dichloro‐2‐propyl) phosphate exposure in adult male rats differ depending on the history of exposure in the neonatal period

“…Serum iron and UIBC are indices that are mainly used in the diagnosis of anemia. From the toxicity results of TDCIPP in 9‐week‐old rats (Kobayashi et al, 2021) and the results of this study, RBC counts and Hb, and Ht levels were decreased along with a decrease in reticulocyte counts. TDCIPP might induce renal anemia by decreasing the production of erythropoietin by the kidneys.…”

“…This study clarified that the toxic effects of exposure to high concentrations of TDCIPP in adulthood are affected by neonatal exposure. We previously reported the effects of high‐dose exposure to TDCIPP over 1 week in 9‐week‐old Wistar–Imamichi male rats and observed hepatotoxicity, nephrotoxicity, spleen atrophy, anemia with decreased reticulocyte counts, and decreased ALP levels (Kobayashi et al, 2021). Similarly, as reported in previous studies, the present investigation identified changes of liver function (increases in liver weight and ALB and ALT levels), changes of kidney function (increases of kidney weight and BUN and CRE levels), and anemia symptoms associated with decreased spleen weight and decreased reticular erythrocyte counts as the main effects of the TDCIPP exposure in adulthood.…”

Effects of tris(1,3-dichloro-2-propyl) phosphate on epididymal sperm parameters in adult male rats

“…In the present study, the effect of 7 days of TDCIPP oral administration on the epididymal sperm parameters was investigated. The present study found that a dose of 250 mg/kg/day, which does not cause overt toxicities [13], affected some of the sperm parameters. Unexpectedly, although antiandrogenic substances typically decrease sperm parameters such as sperm number, motility, and velocity in adulthood [15,18,20,22], TDCIPP induced an increase in some of these parameters.…”

“…13674-87-8, Purity: >93.0%) dissolved in sesame oil (250 mg/kg/day group: n = 6, 650 mg/kg/day group: n = 6) for 7 days. The dose of 650 mg/kg/day caused overt hepatic and renal toxicity, but the dose of 250 mg/kg/day did not [13].…”

“…Tris(1,3dichloro-2-propyl) phosphate (TDCIPP) is an OPFR, and its toxicity is reported [7,19,26]. We recently reported that TDCIPP causes hepatic and renal toxicity, along with a reduction in alkaline phosphatase, and anemia coinciding with a reduction in reticulocyte count [13].…”