Triphosphoric acid aluminium salt

トリリン酸アルミニウム塩


[CAS No. 13939-25-8]

Aluminium triphosphate

Molecular formula: AlH6O12P3　Molecular weight: 317.94

ABSTRACT

Triphosphoric acid aluminium salt was studied for oral toxicity in rats in both a single dose toxicity test at doses of 0 and 2000 mg/kg, and in a combined repeat dose and reproductive/developmental toxicity screening test at doses of 0, 100, 300 and 1000 mg/kg/day, in accordance with the OECD Test Guidelines 401 and 422.

The single dose oral toxicity test revealed an LD50 value of more than 2000 mg/kg for males and females.

With regard to repeated dose toxicity, decreases in total protein and calcium levels were observed in females given 1000 mg/kg. Atrophy of testes and epididymides was observed in males given 300 mg/kg or more. Atrophy of seminiferous tubules in testes, and decrease of spermatozoa in epididymides were observed on histopathological examination.

The NOELs are considered to be 100 mg/kg/day in males and 300 mg/kg/day in females.

With regard to reproductive and developmental toxicity, no effects were observed on reproductive performance in males and females given any dose, or on developmental performance in the pups.

The NOEL for reproductive/developmental toxicity is considered to be 1000 mg/kg/day for reproductive performance and offspring development.

Triphosphoric acid aluminium salt was not mutagenic in Salmonella typhimurium TA100, TA1535, TA98, TA1537 and Escherichia coli WP2 uvrA/pKM101, with or without an exogenous metabolic activation system.

Triphosphoric acid aluminium salt induced structural chromosomal aberrations in CHL/IU cells after short term treatment with an exogenous metabolic activation system. Polyploidy was not induced in any treatment group.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:94.7 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral (gavage)
　Dosage:0 (vehicle), 2000 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:0.5 % Sodium carboxymethylcellulose
GLP:Yes

　Test results:

No deaths occurred in either males or females of the 2000 mg/kg group, and no abnormal changes were observed on clinical observation, body weight determination, or at autopsy.

The LD50 values were estimated to be more than 2000 mg/kg for both sexes.

2. Repeated Dose and Reproductive/Developmental Toxicity 1)

Purity:94.7 %
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 422
　Route:Oral (gavage)
　Dosage:0 (vehicle), 100, 300, 1000 mg/kg
　Number of animals/groupMales, 10; females, 10
　Vehicle:0.5 % Sodium carboxymethylcellulose
　Administration period:Males, 46 days
Females, from 14 days before mating to day 4 of lactation
　Terminal killing:Males, day 47
Females, day 5 of lactation
GLP:Yes

　Test results:

<Repeated dose toxicity>

Decreases in total protein and calcium levels were observed in females given 1000 mg/kg.

Atrophy of testes and epididymides was observed in males given 300 mg/kg or more. Atrophy of seminiferous tubules in testes and decrease of spermatozoa in epididymides were observed on histopathological examination.

The NOELs are considered to be 100 mg/kg/day in males and 300 mg/kg/day in females.

<Reproductive and developmental toxicity>

No effects were observed on reproductive performance in males and females given any dose, or on developmental performance in the pups.

The NOEL for reproductive/developmental toxicity is considered to be 1000 mg/kg/day for reproductive performance and offspring development.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:94.7 %
Test species/strain:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA/pKM101
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:Dimethyl sulfoxide
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98), Sodium azide (TA1535), 9-Aminoacridine hydrochloride (TA1537) and N-Ethyl-N'-nitro-N-nitrosoguanidine (WP2 uvrA/pKM101)
+S9 mix; 2-Aminoanthracene (five strains)
　Dosage:-S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
+S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (five strains)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3
　Number of replicates:2
GLP:Yes

　Test results:

This chemical did not induce gene mutations in the Salmonella typhimurium or Escherichia coli strains. Toxicity was not observed up to 5000 μg/plate in the five strains, with or without metabolic activation.

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

Escherichia coli WP2 uvrA/pKM101
+?-
Without metabolic activation:[ ][ ][*]
With metabolic activation:[ ][ ][*]

3-2. Non-bacterial in vitro test (chromosomal aberration test)2)

Purity:94.7 %
Type of cell used:Chinese hamster CHL/IU cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Solvent:Dimethyl sulfoxide
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Benzo[a]pyrene
　Dosage:-S9 mix (6 hr short-term treatment); 0, 6.25, 12.5, 25, 50, 100 μg/mL
+S9 mix (6 hr short-term treatment); 0, 250, 500, 1000, 1500, 2000 μg/mL (main test)
+S9 mix (6 hr short-term treatment); 0, 1600, 1800, 2000 μg/mL (confirmation test)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

Structural chromosomal aberrations were induced after 6 hr short term treatment with S9 mix (33.0 % at 2000 μg/mL [main test], 11.0 % at 2000 μg/mL [confirmation test]). Polyploidy was not induced in any treatment group.

Lowest concentration producing cytogenetic effects in vitro:
With metabolic activation (short-term treatment):2 mg/mL (clastogenicity)

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

1)The tests were performed by the Safety Research Institute for Chemical Compounds Co., Ltd., 363-24 Shin-ei, Kiyota-ku, Sapporo-shi, Hokkaido, 004-0839, Japan. Tel +81-11-885-5031 Fax +81-11-885-5313
2)The tests were performed by the Mitsubishi Chemical Safety Institute Ltd., 14 Sunayama, Hasaki-machi, Kashima-gun, Ibaraki 314-0255, Japan. Tel +81-479-46-2871 Fax +81-479-46-2874