Diphenyl 2-ethylhexyl phosphate

リン酸 (2-エチルヘキシル)ジフェニルエステル


[CAS No. 1241-94-7]

2-Ethylhexyl diphenyl phosphate

(2-エチルヘキシル)ジフェニルフォスフェート

Molecular formula: C20H27O4P Molecular weight: 362.44

ABSTRACT

Diphenyl 2-ethylhexyl phosphate was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 4, 20, 100 and 500 mg/kg.

A decrease in food consumption was observed in the 500 mg/kg group. Hematological examination revealed prolongation of APTT in the 500 mg/kg group. Blood chemical examination revealed decreases in plasma cholinesterase, blood cell cholinesterase, GOT and ALP and increases in total cholesterol, total protein, and albumin in the 100 and/or 500 mg/kg groups. The liver weights were increased and centrilobular hypertrophy of hepatocytes was histologically noted in the 100 and 500 mg/kg groups. An increase in hyaline droplets of proximal renal tubules was observed in males given 500 mg/kg. Hypertrophy of follicular epithelial cells of the thyroid glands was noted in the 100 and 500 mg/kg groups. The adrenal weights were increased in the 100 and 500 mg/kg groups and histopathologically, an increase in the amounts of lipid droplets in the fascicular zone was observed in the 500 mg/kg group. These changes disappeared or demonstrated a tendency for reduction during the recovery period.

The NOEL for the repeat dose toxicity is considered to be 20 mg/kg/day for both sexes.

Diphenyl 2-ethylhexyl phosphate was not mutagenic in Salmonella typhimurium, TA100, TA1535, TA98, TA1537 or Escherichia coli WP2uvrA. Regardless of the presence or absence of exogenous metabolic activation system, this chemical substance did not induce structural chromosomal aberrations in CHL/IU cells. Polyploidy was also not induced under the conditions of the present study.

SUMMARIZED DATA FROM THE STUDIES

1. Repeat Dose Toxicity１）

Purity:91.4%
Test species/strain:Rat/Crj:CD (SD)
Test method:Guidelines for 28-Day Repeat Dose Toxicity Testing for Chemicals (Japan)
　Route:Oral (gavage)
　Dosage:0 (vehicle), 4, 20, 100, 500 mg/kg/day
　Number of animals/group:Males, 6; females, 6
　Vehicle:0.1% Tween 80 solution
　Administration period:Males and females, 28 days
　Terminal kill:Days 29 or 43
GLP:Yes

　Test results:

Decreased food consumption was noted in females given 500 mg/kg. Hematological examination revealed prolongation of APTT in males given 500 mg/kg. Blood chemical examination revealed: a decrease in plasma cholinesterase in both sexes given 500 mg/kg; a decrease in blood cell cholinesterase in females given 100 mg/kg and in both sexes given 500 mg/kg; an increase in total cholesterol in females given 500 mg/kg; an increase in total protein in males given 100 mg/kg and in both sexes given 500 mg/kg; an increase in albumin in males given 100 and 500 mg/kg; a decrease in GOT in females given 500 mg/kg; and a decrease in ALP in females given 100 and 500 mg/kg. The liver weights were increased in males given 100 mg/kg and in both sexes given 500 mg/kg and histopathologically, hypertrophy of centrilobular hepatocytes was noted in both sexes given 100 and 500 mg/kg. An increase in the amounts of hyaline droplets in the proximal renal tubules was observed in males given 500 mg/kg. Hypertrophy of the follicular epithelial cells of the thyroid glands was noted in both sexes given 100 and 500 mg/kg. The adrenal weights were increased in females given 100 mg/kg and in both sexes given 500 mg/kg and histopathologically, an increase in the amounts of lipid droplets in the fascicular zone in both sexes given 500 mg/kg. These changes disappeared or tended to become reduced during the recovery period.

The NOEL for the repeat dose toxicity is considered to be 20 mg/kg/day for both sexes.

2. Genetic Toxicity

2-1. Bacterial test１）

Purity:91.4 %
Test species/strain:Salmonella typhimurium, TA100, TA1535, TA98, TA1537 Escherichia coli WP2uvrA
Test method:OECD Guidelines No. 471, 472 and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Procedures:Pre-incubation method
　Solvent:DMSO
　Positive controls: -S9 mix, AF-2 (TA100, TA98), Sodium azide (TA1535), ENNG (WP2 uvrA) and 9-Aminoacridine (TA1537)
+S9 mix, 2-Aminoanthracene(all strains)
　Doses:-S9 mix; 313, 625, 1250, 2500, 5000 μg/plate
+S9 mix; 313, 625, 1250, 2500, 5000 μg/plate
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plate/test:3
　Number of replicates:2
GLP:Yes

　Test results:

This chemical did not induce mutations in the S. typhimurium and E. coli strains. No toxicity was observed up to a concentration of 5000 μg/plate with or without metabolic activation.

Genotoxic effects:
S. typhimurium, TA100, TA1535, TA98, TA1537
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

E. coli WP2 uvrA
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

2-2. Non-bacterial in vitro test (chromosomal aberration test)１）

Purity:91.4 %
Type of cell used:Chinese hamster CHL/IU cells
Test method:OECD Guidelines No. 473 and Guidelines for Screening Mutagenicity Testing of Chemicals (Japan)
　Solvent:acetone
　Positive controls:-S9 mix, Mitomycin C
+S9 mix, Benzo[a]pyrene
　Doses:-S9 mix (24 hr continuous treatment): 0, 6.25, 12.5, 25, 50 μg/ml
-S9 mix (48 hr continuous treatment): 0, 3.13, 6.25, 12.5, 25 μg/ml
-S9 mix (6 hr short-term treatment): 0, 10, 20, 40, 80 μg/ml
+S9 mix (6 hr short-term treatment): 0, 25, 50, 100, 200 μg/ml
　S-9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plate/test:2
GLP:Yes

　Test results:

This chemical did not induce structural chromosomal aberrations or polyploidy under the conditions of this experiment.

Genotoxic effects:
clastogenicitypolyploidy
+?-+?-
Without metabolic activation:[ ][ ][*][ ][ ][*]
With metabolic activation:[ ][ ][*][ ][ ][*]

1)The tests were performed by the Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki, 314-02, Japan. Tel +81-479-46-2871 Fax +81-479-46-2874