Silicone nitride

窒化ケイ素

[CAS No. 12033-89-5]

Molecular formula: N₄Si₃　Molecular weight: 140.28

ABSTRACT

Silicon nitride was studied for oral toxicity in rats in a 28-day repeated dose toxicity test at doses of 0, 100, 300, and 1000 mg/kg/day.

Neither dead nor moribund animals were noted in either sex in any group. No changes attributable to the test substance were noted in general signs, body weights, food consumption, water intake, urinalysis, hematological examination, blood chemical analysis, necropsy findings, organ weights, or histopathological findings.

The NOEL for the 28-day repeated dose toxicity of silicone nitride is considered to be 1000 mg/kg/day for both sexes.

Silicone nitride was studied for oral toxicity in rats in an OECD preliminary reproduction toxicity screening test at doses of 0, 100, 300 and 1000 mg/kg/day.

With regard to repeated dose toxicity, no deaths were observed in any group. No effects related to administration of the test substance were observed on clinical signs, body weight, food consumption, necropsy, organ weight or histopathological examination in any treatment group. The NOEL is therefore considered to be 1000 mg/kg/day for repeated dose toxicity.

In terms of reproductive/developmental toxicity, there were no effects related to administration of the test substance on the reproductive performance of the parents or development of the next generation. The NOEL is therefore considered to be 1000 mg/kg/day for reproductive performance of the parents and for development of the offspring.

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

Silicone nitride did not induce structural chromosomal aberrations nor polyploidy in CHL/IU cells with or without an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity ¹⁾

Purity	:	ca. 97 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 401
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 250, 500, 1000, 2000 mg/kg
Number of animals/group	:	Males, 5; females, 5
Vehicle	:	0.5 % Sodium carboxymethylcellulose
GLP	:	Yes

　Test results:

No deaths were observed in either sex. No abnormalities were noted in general signs, body weight change, or necropsy findings. LD₅₀ values were estimated to be more than 2000 mg/kg for both sexes.

2. Repeat Dose Oral Toxicity ¹⁾

Purity	:	ca. 97 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	Guideline for the 28-Day Repeated Dose Toxicity Test in Mammalian Species (Chemical Substances Control Law of Japan)
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 100, 300, 1000 mg/kg
Number of animals/group		Males, 12; females, 12 (0, 300, 1000 mg/kg) Males, 6; females, 6 (100 mg/kg)
Vehicle	:	0.5 % Sodium carboxymethylcellulose
Administration period	:	Males and females, 28 days
Terminal killing	:	Males and females, day 29 or 43
GLP	:	Yes

　Test results:

Neither dead animals nor moribund animals were noted in any group. No abnormal signs were noted in any group. No changes caused by the test substance were noted in body weights, food consumption, or water intake. No changes caused by the test substance were noted in the urinalysis, hematological examination, or blood chemical analysis. Changes caused by the test substance were not noted in necropsy findings, organ weights, or histopathological findings.

The NOEL for the 28-day repeated dose toxicity of silicone nitride is considered to be 1000 mg/kg/day for both sexes.

3. Preliminary Reproduction Toxicity ²⁾

Purity	:	ca. 97.0 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 421
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 100, 300, 1000 mg/kg/day
Number of animals/group		Males, 12; females, 12
Vehicle	:	0.5 % Sodium carboxymethylcellulose
Administration period	:	Males, 49 days Females, from 14 days before mating to day 3 of lactation
Terminal killing	:	Males, day 50 Females, day 4 of lactation
GLP	:	Yes

　Test results:

<Repeated dose toxicity>

No deaths occurred in any group. There were no changes in clinical signs, body weight, food consumption, necropsy, organ weight or histopathological examination in the silicone nitride groups. The NOEL for repeated dose toxicity is considered to be 1000 mg/kg/day for males and females.

<Reproductive and developmental toxicity>

As concerns reproductive performance, no effects related to administration of the test substance were observed on the estrous cycle, numbers of corpora lutea or implantations, copulation index or fertility indices for the males or females. On examination at delivery and during the lactation period, no effects related to administration of the test substance were observed on the gestation days, number of litters or live newborn, gestation index, stillbirth index, birth index, sex ratio, body weights of offspring at birth or on day 4 after birth, or the viability index on day 4. There were no external anomalies in any group. The NOEL is considered to be 1000 mg/kg/day for both the reproductive performance of the parents and development of the offspring.

4. Genetic Toxicity

4-1. Bacterial test ³⁾

Purity	:	ca. 97 %
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:	[ ]	[ ]	[*]

4-2. Non-bacterial in vitro test (chromosomal aberration test)³⁾

Purity	:	ca. 97 %
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
Vehicle	:	Isotonic sodium chloride solution
Positive controls	:	-S9 mix; Mitomycin C +S9 mix; Benzo[a]pyrene
Dosage	:	-S9 mix (6 hr short-term treatment); 0, 12.5, 25, 50, 100, 200, 400 μg/mL +S9 mix (6 hr short-term treatment); 0, 100, 200, 400, 800, 1600, 2400 μg/mL -S9 mix (24 hr continuous treatment); 0, 50, 100, 200, 300, 400, 500 μg/mL
S9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

This chemical did not induce structural chromosomal aberrations nor polyploidy under the conditions of this experiment.

Genotoxic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
Without metabolic activation:	[ ]	[ ]	[*]	[ ]	[ ]	[*]
With metabolic activation:	[ ]	[ ]	[*]	[ ]	[ ]	[*]

1)	The tests were performed by Nihon Bioresearch Inc., 6-104, Majima, Fukuju-cho, Hashima, Gifu, 501-6251, Japan. Tel +81-58-392-6222 Fax +81-58-392-1284
2)	The test was performed by the Safety Assessment Laboratory, Panapharm Laboratories Co., Ltd., 1285 Kurisaki-machi, Uto-shi, Kumamoto, 869-0425, Japan. Tel +81-964-23-5111 Fax +81-964-23-2282
3)	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