2-(1-Methylethoxy)ethanol

2-(1-メチルエトキシ)エタノール

[CAS No. 109-59-1]

Ethyleneglycol iso-propyl ether/2-iso-Propoxyethanol

エチレングリコールイソプロピルエーテル/2-イソプロポキシエタノール

Molecular formula: C₅H₁₂O₂　Molecular weight: 104.15

ABSTRACT

A twenty-eight-day repeated dose oral toxicity test of 2-(1-methylethoxy)ethanol was carried out in rats at doses of 30, 125 and 500 mg/kg in accordance with the guideline for the 28-day repeated dose toxicity test in mammalian species (Chemical substances control law of Japan).

Transient hematurea appeared in the 500 mg/kg dose group in both sexes after the first administration but this subsided on subsequent administration. Anemia and extramedullary hematopoiesis in the liver and the spleen were observed in both sexes. On myelogram examination, erythroid cells were found to be increased in all treated groups. The NOEL for repeated dose toxicity was considered to be less than 30 mg/kg/day for both sexes.

A preliminary reproductive toxicity screening test of 2-(1-methylethoxy)ethanol by oral administration in rats was carried out in accordance with the OECD test guideline 421.

After the first administration, hematuria appeared in males at 125 mg/kg and in females at 30 mg/kg and above. At the end of the administration period, spleen weights were increased in both sexes at 125 mg/kg. No other alteration was observed regarding body weights, food consumption or any reproductive or developmental parameters.

The NOELs for repeated dose toxicity were considered to be 30 mg/kg/day for males and 8 mg/kg/day for females and for reproductive and developmental toxicity were considered to be 125 mg/kg/day for parental males and females, and offspring.

Reverse mutation assays using microorganisms (Salmonella typhimurium, Escherichia coli) were conducted to assess the potential of 2-(1-methylethoxy)ethanol to induce gene mutations.

2-(1-Methylethoxy)ethanol did not induce gene mutations in bacteria under the conditions of this study.

In vitro chromosomal aberration tests using cultured Chinese hamster cells (CHL/IU) were conducted to assess the potential of 2-(1-methylethoxy)ethanol to induce chromosomal aberrations.

2-(1-Methylethoxy)ethanol 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	:	> 99.5 %
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	:	Water for injection
GLP	:	Yes

　Test results:

No deaths occurred in either sex. Reddish urine was found in all animals of both sexes of the 2000 mg/kg group from 3 or 4 hours after treatment. This change was also observed on the next day in the same group. Fecal volume was decreased in several animals of the 2000 mg/kg group on the day after administration. Body weights of treated animals tended to be lower than those of the control group. No macroscopic abnormalities were observed in any animals at autopsy.

The LD₅₀ value was concluded to be above 2000 mg/kg for both sexes.

2. Repeated Dose Oral Toxicity ¹⁾

Purity	:	> 99.5 %
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), 30, 125, 500 mg/kg/day
Number of animals/group		Males, 10; females, 10 (0, 500 mg/kg) Males, 5; females, 5 (30, 125 mg/kg)
Vehicle	:	Water for injection
Administration period	:	Males and females, 28 days
Terminal killing	:	Males and females, days 29 and 43
GLP	:	Yes

　Test results:

After the first administration, hematuria appeared in the 500 mg/kg dose group in both sexes. With 125 mg/kg and above, the RBC count, hemoglobin concentration and hematocrit were decreased and mean corpuscular constants were changed in both sexes. On histopathological observation, extramedullary hematopoiesis was apparent in the liver after treatment with 500 mg/kg. Furthermore, in the spleen, extramedullary hematopoiesis and deposits of brown pigment appeared with 125 mg/kg and above. In the medulla, erythroid cells were increased in all groups of both sexes. The NOEL for repeated dose toxicity was considered to be less than 30 mg/kg/day for both sexes.

3. Preliminary Reproductive Toxicity ¹⁾

Purity	:	> 99.5 %
Test species/strain	:	Rat/Crj:CD(SD)IGS
Test method	:	OECD Test Guideline 421
Route	:	Oral (gavage)
Dosage	:	0 (vehicle), 8, 30, 125 mg/kg/day
Number of animals/group		Males, 13; females, 13
Vehicle	:	Water for injection
Administration period	:	Males, 48 days Females, from 14 days before mating to day 3 of lactation
Terminal killing	:	Males, 49 days Females, day 4 of lactation
GLP	:	Yes

　Test results:

<Repeat dose toxicity>

After the first administration, hematuria appeared in males at 125 mg/kg and in females at 30 mg/kg and above. At the end of the administration period, spleen weights were increased in both sexes at 125 mg/kg. No alterations were observed regarding body weights, food consumption or pathological findings in either sex. The NOELs for repeated dose toxicity were considered to be 30 mg/kg/day for males and 8 mg/kg/day for females.

<Reproductive and developmental toxicity>

No alterations were observed for any reproductive or developmental parameters. The NOEL for reproductive and developmental toxicity was considered to be 125 mg/kg/day for parental males and females, and offspring.

4. Genetic Toxicity

4-1. Bacterial test ²⁾

Purity	:	> 99.5 %
Test species/strains	:	Salmonella typhimurium TA100, TA1535, TA98, TA1537, Escherichia coli WP2 uvrA
Test method	:	Guidelines for Screening Mutagenicity Testing of Chemicals (Chemical Substances Control Law of Japan) and OECD Test Guideline 471
Procedures	:	Pre-incubation method
Vehicle	:	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)
Dosage	:	-S9 mix; 0, 8.19, 20.5, 51.2, 128, 320, 800, 2000, 5000 μg/plate (all strains for the dose-finding study) +S9 mix; 0, 8.19, 20.5, 51.2, 128, 320, 800, 2000, 5000 μg/plate (all strains for the dose-finding study) -S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (all strains for the main study) +S9 mix; 0, 313, 625, 1250, 2500, 5000 μg/plate (all strains for the main study)
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 mix) or the activation method (+S9 mix).

Genetic effects:
Salmonella typhimurium TA100, TA1535, TA98, TA1537

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

Escherichia coli WP2 uvrA

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

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

Purity	:	> 99.5 %
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
Vehicle	:	Water for injection
Positive controls	:	-S9 mix; Mitomycin C +S9 mix; Cyclophosphamide
Dosage	:	-S9 mix (short-term treatment); 0, 263, 525, 1050 μg/mL +S9 mix (short-term treatment); 0, 263, 525, 1050 μg/mL -S9 mix (continuous treatment 24 hr); 0, 263, 525, 1050 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 (-S9 mix and +S9 mix) or the continuous treatment.

Genetic effects:

	clastogenicity			polyploidy
	+	?	-	+	?	-
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