Tetramethylammonium hydroxide

テトラメチルアンモニウムヒドロキシド


[CAS No. 75-59-2]

Molecular formula: C4H13NO　Molecular weight: 91.15

ABSTRACT

A single dose oral toxicity test of tetramethylammonium hydroxide revealed an LD50 value of between 34 to 50 mg/kg for males.

Tetramethylammonium hydroxide was studied for oral toxicity in rats in a 28-day repeat dose toxicity test at doses of 0, 5, 10 and 20 mg/kg. No deaths were observed in either sex. The animals repeatedly showed salivation after administration in the groups given 10 mg/kg and more. In the male animals, heart weight was decreased dose-dependently, and in the groups given 5 mg/kg and more the absolute heart weights were significantly less than the control group value. Thus, the NOELs for the 28-day repeat dose oral toxicity test of tetramethylammonium hydroxide are considered to be less than 5 mg/kg/day for males and 5 mg/kg/day for females.

Reverse mutation assays using microorganisms (Salmonella typhimurium, Escherichia coli) were conducted to assess the potential of tetramethylammonium hydroxide to induce gene mutations. Tetramethylammonium hydroxide did not induce gene mutations in bacteria under the conditions of this study.

In vitro chromosomal aberration tests using cultured cells (CHL/IU) were conducted to assess the potential of tetramethylammonium hydroxide to induce chromosomal aberrations. Tetramethylammonium hydroxide did not induce chromosomal aberrations in cultured cells under the conditions of this study.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity 1)

Purity:20.19 %(water solution)
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:OECD Test Guideline 401
　Route:Oral(gavage)
　Doses:Males, 10, 15, 23, 34, 50 mg/kg
Females, 23 mg/kg
　Number of animals/group:Males, 5; females, 5
　Vehicle:Water for injection
GLP:Yes

　Test results:

Death occurred in male rats of the 34 mg/kg and more groups. In the animals, which died clinical signs of decrease in locomotor activity, hypothermia, incomplete eyelid opening or eyelid closure, an ataxic gait, clonic convulsions, salivation and bradypnea were observed. Body weights of the male rats given 34 mg/kg and more were lower than those of the other groups. No macroscopic abnormalities were observed in any animals at autopsy.

The LD50 value was concluded to be between 34 to 50 mg/kg for males.

2. Repeat Dose Toxicity 1)

Purity:20.19 %(water solution)
Test species/strain:Rat/Crj:CD(SD)IGS
Test method:Guideline for 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
　Route:Oral(gavage)
　Doses:0(vehicle), 5, 10, 20 mg/kg/day
　Number of animals/group:Males, 10; females, 10(0, 20 mg/kg)
Males, 5; females, 5(5, 10 mg/kg)
　Vehicle:Water for injection
　Administration period:Males and females, 28 days
　Terminal kill:Males and females, on days 29 and 43
GLP:Yes

　Test results:

In the repeat dose study, no deaths were observed in either sex. On the 6th day of administration and later, the animals repeatedly showed salivation after administration in the groups given 10 mg/kg and more. In male animals of the 10 mg/kg group and animals of both sexes in the 20 mg/kg group, food consumption was decreased significantly in the 1st week of administration as compared with that in the control group. During the recovery period, food consumption became increased in the male animals previously given the test substance and the increase was significant in the 1st week of recovery. Urinary electrolyte excretion in the male test substance groups increased significantly in the 2nd week of the recovery period. The heart weights of male animals decreased dose-dependently. The absolute values in the animals given 5 mg/kg and more, and the relative heart to body weights in the animals given 10 mg/kg and more were thus significantly decreased. On the other hand, neither the female animals at the end of the administration period nor the animals of either sex at the end of the recovery period showed any significant changes in organ weights which were thought to have relevance to the test substance administered. Moreover, in the histopathological examination there were no changes attributable to the test substance administered.

Thus, the NOELs for the 28-day repeat dose toxicity are considered to be less than 5 mg/kg/day for males and 5 mg/kg/day for females.

3. Genetic Toxicity

3-1. Bacterial test 2)

Purity:20.0 %
Test species/strains:Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals(Chemical Substance Control Law of Japan) and OECD Test Guideline 471
　Procedures:Pre-incubation method
　Solvent:Water for injection
　Positive controls:-S9 mix; 2-(2-Furyl)-3-(5-nitro-2-furyl)acrylamide (TA100, TA98 and WP2 uvrA), Sodium azide (TA1535) and 9-Aminoacridine hydrochloride (TA1537)
+S9 mix; 2-Aminoanthracene (all strains)
　Doses:-S9 mix; 39.1, 78.1, 156, 313, 625, 1250 μg/plate(all strains)
+S9 mix; 39.1, 78.1, 156, 313, 625, 1250 μg/plate(TA100, TA1535, TA98 and TA1537)
+S9 mix; 156, 313, 625, 1250, 2500, 5000 μg/plate(WP2 uvrA)
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:3
　Number of replicates:2
GLP:Yes

　Test results:

No increase in revertant colonies was observed in the test with either the non-activation method (-S9) or activation (+S9).

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

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

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

Purity:20.0 %
Type of cell used:Chinese hamster lung (CHL/IU) cells
Test method:Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 473
　Solvent:Water for injection
　Positive controls:-S9 mix; Mitomycin C
+S9 mix; Cyclophosphamide
　Doses:-S9 mix(short-term treatment); 0, 228, 455, 910 μg/mL
+S9 mix(short-term treatment); 0, 228, 455, 910 μg/mL
-S9 mix(continuous treatment 24 hr); 0, 228, 455, 910 μg/mL
　S9:Rat liver, induced with phenobarbital and 5,6-benzoflavone
　Plates/test:2
GLP:Yes

　Test results:

No increase in chromosomal aberrations was observed in the test with either the short-term treatment (-S9 and +S9) or continuous treatment.

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

1)The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257-8523, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627
2)The tests were performed by the Biosafety Research Center, Foods, Drugs and Pesticides (An-pyo Center), 582-2 Shioshinden, Fukude-cho, Iwata-gun, Shizuoka, 437-1213, Japan. Tel +81-538-58-1266 Fax +81-538-58-1393