NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	108-62-3
Chemical Name	2,4,6,8-Tetramethyl-1,3,5,7-tetraoxacyclooctane
Substance ID	m-nite-108-62-3_v2
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecules.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Flammable solids	Category 2	Warning	H228	P370+P378 P210 P240 P241 P280	The substance is classified into Division 4.1, PG III in UNRTDG (UN1332).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Pyrophoric solids	Not classified	- -	-	-	The substance does not fall into upper Division 4.2 (Substances liable to spontaneous combustion) since it is classified into Division 4.1, PG III in UNRTDG (UN1332).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Self-heating substances and mixtures	Not classified	- -	-	-	The substance is judged not fall into upper Division 4.2 since it is classified into Division 4.1 in UNRTDG (UN1332).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (Not applicable)	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen which is chemically bonded only to carbon.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	Based on a LD50 value of 283 mg/kg for rats (EPA RED (2006), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)), the substance was classified into Category 3.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on a LD50 value of 5000 mg/kg and higher for rats (EPA RED (2006), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)), the substance was classified as "Not classified".	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
1	Acute toxicity (Inhalation: Dusts and mists)	Not classified	- -	-	-	Based on a LC50 value (4h) of 314 mg/L for rats (EPA RED (2006)), the substance was classified as "Not classified". Since the saturated vapour pressure is 0.0064 mg/L at room temperature, the test was considered to be conducted for dust or mist.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
2	Skin corrosion/irritation	Not classified	- -	-	-	Based on a report of "not irritant" in a rabbit test (EPA RED (2006), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	Based on a report of "mild irritant" in a rabbit test (EPA RED (2006), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
4	Skin sensitization	Not classified	- -	-	-	Based on a result of not sensitizing (positive ratio: 0.8%, 1/12) in a Buehler guinea pig skin sensitization test (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)) and results of not sensitizing for 30% flowable (positive ratio: 0%, 0/25) and 10% granule (positive ratio: 0%, 0/20) in a maximization test and Buehler test, respectively, (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)), the substance was classified as "Not classified".	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
5	Germ cell mutagenicity	Not classified	- -	-	-	Based on a negative result in an oral mouse bone marrow micronucleus test (in vivo somatic cell mutagenicity tests) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)), the substance was classified as "Not classified". As relevant information, from in vitro mutagenicity tests, there are reports of a negative Ames test and a negative CHO cell chromosomal aberration test (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
6	Carcinogenicity	Classification not possible	- -	-	-	Although there is a report that no tumorgenicity was observed in a mouse 78-week feeding test (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)), there is also a report that incidence of hepatocellular adenomas and incidence of combined hepatocellular adenomas and carcinomas were increased in females of the highest dose group in a rat 2-year feeding combined toxicity/carcinogenicity test (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)). Since evidence of carcinogenic activity was observed in female rats only and not in males, classification was not possible.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." Besides, in the EU, it was classified in Repr. 2 because testis toxicity was observed in a repeated dose toxicity study with dogs based on (5), but since there was no evidence of adverse effects on fertility in test animals, it was not adopted for the classification. [Evidence Data] (1) In a two-generation reproduction toxicity study with rats dosed by feeding (GLP, 50 to 2,000 ppm), no effects on fertility were observed in parent animals up to 2,000 ppm (134 to 164 mg/kg/day) at which hind limb paralysis, spinal fracture/luxation, and hemorrhage/necrosis of the spinal cord were observed in females of the P generation, and increases in absolute and/or relative liver weight were observed in F1 males and females. In offspring, only reduced body weight gain was observed in F1 and F2 female pups (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018), CLH Report (2016), ECHA RAC Opinion (Background Doc.) (2017)). (2) In a developmental toxicity study (GLP, 25 to 150 mg/kg/day) with female rats dosed by gavage on days 6 to 15 of gestation, no developmental effects were observed in fetuses up to the highest dose (150 mg/kg/day) at which death (6/25 animals), reduced body weight and food consumption, dilated renal pelvis, hydronephrosis, and paravertebral hemorrhages were observed in dams (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018), CLH Report (2016), ECHA RAC Opinion (Background Doc.) (2017)). (3) In a developmental toxicity study (GLP, 10 to 80 mg/kg/day) with female rabbits dosed by gavage on days 6 to 18 of gestation, no abnormalities were observed both in dams and fetuses up to the highest dose. In a preliminary test for dose settings, deaths were observed in dams at 100 mg/kg/day, and therefore, the highest dose in the test was set to 80 mg/kg/day (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2018), CLH Report (2016), ECHA RAC Opinion (Background Doc.) (2017)). (4) Based on (1) to (3), no effects on fertility nor teratogenicity were observed after administration of this substance (Risk Assessment Report (Pesticide) (Food Safety Commission of Japan, 2017)). [Reference Data, etc.] (5) Based on (1) to (3), no reproduction developmental effects were detected, but in 52-week chronic toxicity studies with dogs, testis toxicity (bilateral localized atrophy of the testis) was observed, which might adversely affect fertility. No testis toxicity was observed in rats, but the possibility of a difference between the species cannot be ruled out. This substance was classified in Repr. 2 by the ECHA RAC (Committee for Risk Assessment of the European Chemical Agency) based on the testis toxicity in chronic toxicity studies with dogs (ECHA RAC Opinion (2017)). (6) In the EU, it was classified in Repr. 2 (EU-CLP Classification Results (Accessed Nov. 2021)).	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	Convulsions (for 3 days), coma (for 7 days) and memory loss were caused in humans following accidental ingestion of metaldehyde (PIMs (1999)). Hunchback position, lethargy and piloerection were observed in rats after an oral administration at dose levels of 100 - 800 mg/kg and sporadic signs included ataxia, whole body tremor and tonic convulsion (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)). Additionally, in a mouse oral test, 9/10 and 10/10 mice exhibited tonic flexion and extension convulsion at dose levels of 30 and 100 mg/kg (both within the guidance value range for Category 1), respectively, (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)). Based on this information, the substance was classified into Category 1 (nervous system).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
9	Specific target organ toxicity - Repeated exposure	Category 2 (nervous system, liver, testis)	Warning	H373	P260 P314 P501	In a rat 107-week feeding test, hind-limb paralysis was observed at dose levels of 20 - 100 mg/kg bw/day and lesions of the spinal cord were observed in the top dose (JMPR WHO/FAO Data Sheets on Pesticides No. 93 (1996)). In a dog 52-week feeding test, symptoms such as ataxia, tremors and convulsions as well as histopathological findings such as testicular giant cells, atrophy and degeneration of the germinative epithelium and atrophy of the prostate were observed (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)). Since these findings were observed at dos levels within the guidance value range for Category 2, the substance was classified into Category 2 (nervous system, testis). In addition, in a rat 90-day feeding test, liver histopathological changes (centrilobular hepatocyte hypertrophy) were observed in both sexes at 750 and 2500 ppm (approximately 37.5 and 125 mg/kg/day). In a mouse 90-day feeding test, hepatocellular necrosis, hypertrophy, hyperplasia, inflammation, anisokaryosis and vacuolization were observed at 1000 ppm, and the same lesions in minimal degree were observed at 100 and 300 ppm (15 and 45 mg/kg/day) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center) (2009)). Based on this information, the substance was classified into Category 2 (liver).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Not classified	- -	-	-	Classified into Not classified from its 96h-LC50 = 149.8 mg/L for fish (Bluegill) (AQUIRE, 2010).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Classified into Not classified since its acute toxicity is Not classified and it is not non-water soluble (Water solubility: 222 mg/L (PHYAPROP Database, 2009) and is low bioconcentration potential (LogKow = 0.22 (Biodegradation and Bioconcentration of Existing Chemical Substances under the Chemical Substances Control Law, 2004)).	FY2009	GHS Classification Guidance by the Japanese Government （March, 2009）
12	Hazardous to the ozone layer	-	- -	-	-	-	-	-

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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