Pentaerythritol

ペンタエリスリトール

CAS No. 115-77-5

Tetramethylolmethane / 2,2-Bis(hydroxymethyl)-1,3-propanediol

テトラメチロールメタン／2,2-ビス（ヒドロキシメチル）-1,3-プロパンジオール

Molecular formula: C5H12O4

Molecular weight: 136.17

ABSTRACT

The single dose toxicity test revealed LD50 values of above 2000 mg/kg for both sexes.

In the repeat dose toxicity test, soft feces and diarrhea were observed in both sexes of the 300 and 1000 mg/kg groups and an increase in water consumption was observed in males of the 1000 mg/kg group. The NOELs for repeat dose toxicity for both sexes are considered to be 100 mg/kg/day. No effects were observed on reproductive performance in either sex or on development of the next generation. The NOELs for reproductive and developmental performances are considered to be over 1000 mg/kg/day.

Pentaerythritol was not mutagenic in Salmonella typhimurium TA100, TA98, TA1535, TA1537 and Escherichia coli WP2 uvrA.

Neither structural chromosomal aberrations nor polyploidy were induced in CHL/IU cells up to the limit concentration of 10 mM, in the absence or presence of an exogenous metabolic activation system.

SUMMARIZED DATA FROM THE STUDIES

1. Single Dose Oral Toxicity

Purity	:	92.7%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	OECD Test Guideline 401
Dosage	:	500, 1000, 2000 mg/kg
Number of animals	:	Male, 5; female, 5/group
GLP	:	Yes

　Test results:

Rats of both sexes of the 1000 and 2000 mg/kg groups showed diarrhea and soft feces on the administration day or the following day. However, no deaths occurred of either sex of any treated group, and no changes were observed in terms of body weights, autopsy or histopathology findings.

LD50: Male, >2000 mg/kg; female, >2000 mg/kg

2. Repeat Dose and Reproductive/Developmental Toxicity

Purity	:	92.7%
Test species/strain	:	Rat/Crj:CD (SD)
Test method	:	OECD Combined Repeat Dose and Reproductive/ Developmental Toxicity Screening Test
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 100, 300, 1000 mg/kg/day
Number of animals	:	Males, 12; females, 12/group
Vehicle	:	0.5% CMC-Na solution
Administration period	:	Males, 46 days Females, from 14 days before mating to Day 3 of lactation
Terminal kill	:	Males, day 47 Females, day 4 of lactation
GLP	:	Yes

　Test results:

<Repeat dose toxicity>

Soft feces were noted in rats of both sexes of the 300 and 1000 mg/kg groups, and diarrhea was noted in males of the 300 and 1000 mg/kg groups and females of the 1000 mg/kg group. Water consumption increased in males of the 1000 mg/kg group. No effects were observed in body weights, food consumption, urinalysis, hematology, blood chemistry, organ weight, autopsy or histopathology findings. The NOELs for repeat dose toxicity for both sexes are considered to be 100 mg/kg/day.

<Reproductive and developmental toxicity>

No effects were observed on the following items: for dams, reproductive ability, organ weights histopathological appearance of the reproductive organs, delivery or maternal behavior, and for offspring, viability, clinical signs, body weight changes or autopsy findings. The NOELs for reproductive and developmental performances are considered to be over 1000 mg/kg/day.

3. Genetic Toxicity

3.1 Bacterial test2)

Purity	:	92.7%
Test species/strains	:	S.typhimurium TA100, TA1535, TA98, TA1537 E. coli WP2 uvrA (SD)
Test methods	:	Guideline for Screening Mutagenicity Testing of Chemicals (Japan)
Procedures	:	Plate incorporation method
Solvent	:	Pure water
Positive controls	:	-S9, AF-2 (TA100, WP2, TA98), sodium azide (TA1535) and 9-aminoacridine (TA1537)
		+S9, 2-aminoanthracene (all strains)
Doses	:	0, 312.5, 625, 1250, 2500, 5000 μg/plate
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	3
Number of replicates	:	2
GLP	:	Yes

　Test results:

Minimum concentration of test substance at which toxicity was observed:

No toxicity was observed up to a concentration of 5000 μg/plate with or without S9 Mix

　Genetic effects:

S. typhimurium TA100, TA1535, TA 98, TA1537

	+	?	-
without metabolic activation:	[ ]	[ ]	[*]
with metabolic activation:	[ ]	[ ]	[*]

E. coli WP2 uvrA

	+	?	-
without metabolic activation:	[ ]	[ ]	[*]
with metabolic activation:	[ ]	[ ]	[*]

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

Purity	:	92.7%
Type of cell used	:	Chinese hamster lung (CHL/IU) cells
Test method	:	Guidelines for Screening Mutagenicity Testings of Chemicals (Japan)
Solvent	:	Water for injection
Positive controls	:	-S9, Mitomycin C +S9, Cyclophosphamide
Doses	:	-S9 (continuous treatment): 0, 0.4, 0.7, 1.4 mg/ml -S9 (short-term treatment): 0, 0.4, 0.7, 1.4 mg/ml +S9 (short-term treatment): 0, 0.4, 0.7, 1.4 mg/ml
S-9	:	Rat liver, induced with phenobarbital and 5,6-benzoflavone
Plates/test	:	2
GLP	:	Yes

　Test results:

Cytogenetic effects were not seen under the conditions of this experiment.

　Genotoxic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
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, Toyohira-ku, Sapporo, Hokkaido, 004, Japan. Tel +81-11-885-5031 Fax +81-11-885-5313
2)	The tests were performed by the Hatano Research Institute, Food and Drug Safety Center, 729-5 Ochiai, Hadano-shi, Kanagawa, 257, Japan. Tel +81-463-82-4751 Fax +81-463-82-9627