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GHS Classification Result

GENERAL INFORMATION

Item	Information
CAS RN	107-46-0
Chemical Name	Hexamethyldisiloxane
Substance ID	H30-B-010-METI, MOE
Classification year (FY)	FY2018
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/Ministry of the Environment (MOE)
New/Revised	Revised
Classification result in other fiscal year	FY2011
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)	MHLW Website (in Japanese Only)
Model SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	eChemPortal

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	Not applicable	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases (including chemically unstable gases)	Not applicable	- -	-	-	Liquid (GHS definition)
3	Aerosols	Not applicable	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not applicable	- -	-	-	Liquid (GHS definition)
5	Gases under pressure	Not applicable	- -	-	-	Liquid (GHS definition)
6	Flammable liquids	Category 2	Danger	H225	P303+P361+P353 P370+P378 P403+P235 P210 P233 P240 P241 P242 P243 P280 P501	It was classified in Category 2 based on a flash point of -8 deg C (closed cup) and a boiling point of 100 deg C (GESTIS (Access Dec. 2018)).
7	Flammable solids	Not applicable	- -	-	-	Liquid (GHS definition)
8	Self-reactive substances and mixtures	Not applicable	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9	Pyrophoric liquids	Not classified	- -	-	-	It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 310 deg C (GESTIS (Access Dec. 2018)).
10	Pyrophoric solids	Not applicable	- -	-	-	Liquid (GHS definition)
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	There is a metalloid (Si) present in the molecule. However, because data of water solubility: 0.93 mg/L (25 deg C) (HSDB (Access Dec. 2018)) were obtained, it is estimated that it does not react vigorously with water.
13	Oxidizing liquids	Classification not possible	- -	-	-	It is an organic compound which does not contain fluorine or chlorine but contains oxygen, and the oxygen is chemically bonded to the element other than carbon or hydrogen (Si). However, the classification is not possible due to no data.
14	Oxidizing solids	Not applicable	- -	-	-	Liquid (GHS definition)
15	Organic peroxides	Not applicable	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	No data available.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: > 12,160 mg/kg (male, female) (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)) (2) LD50 for rats: > 3,819 mg/kg (male, female) (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)) (3) LD50 for rats: > 3,200 mg/kg (male) (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: 12,160 mg/kg (male), > 12,160 mg/kg (female) (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)) (2) LD50 for rabbits: > 10,000 mg/kg (male, female) (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)) (3) LD50 for rats: > 2,000 mg/kg (male, female) (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018))
1	Acute toxicity (Inhalation: Gases)	Not applicable	- -	-	-	[Rationale for the Classification] Liquid (GHS definition)
1	Acute toxicity (Inhalation: Vapours)	Category 4	Warning	H332	P304+P340 P261 P271 P312	[Rationale for the Classification] Based on (1), it was classified in Category 4. Besides, the test concentration was lower than 90% of the saturated vapor pressure (360 mg/L (54,294 ppm)), so the reference values in units of ppm were applied. The category was changed by using new information sources. [Evidence Data] (1) LC50 (4 hours) for rats: 106 mg/L (15,956 ppm) (male, female) (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018), Patty (6th, 2012)).
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] No irritation was observed in (4) in the reliable animal data, but irritation was observed in (1)-(3) of repeated dose studies in humans and animals, and based on the weight of evidence, it was classified in Category 2. Besides, the category was changed by using new information sources. [Evidence Data] (1) There is a report that when the undiluted liquid of this substance was applied occlusively to the skin of 100 subjects (finally 100 subjects out of 11 men and 97 women between 18 to 78 years of age) for 24 hours 9 times at 48 hour intervals (from the third application, semi-occlusive application), superficial skin erosion was observed in a considerable number of subjects after the second application, and no irritation was observed after semi-occlusive application (SIAR (2011), Patty (6th, 2012), NICNAS IMAP (Accessed Dec. 2018), REACH registration dossier (Accessed Dec. 2018)). (2) There is a report that when an undiluted solution of this substance was applied to the skin of 64 humans under a non-occlusive dressing for 48 hours, followed by removal of the patch, and then was applied to the same site in the same manner a total of 10 times, skin irritation (redness and swelling) was seen in 10/64 subjects in the first week (SIDS Dossier (2011)). (3) There is a report that in a 24-hour repeated application test with rabbits (CTFA guideline, GLP-compliant), this substance was applied 10 times during 14 days under 3 conditions of occluded, semi-occluded or non-occluded, skin irritation was not observed in either semi-occlusive or non-occlusive applications, but skin irritation was observed on Day 4 in occlusive applications (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018), REACH registration dossier (Accessed Dec. 2018)). [Reference Data, etc.] (4) There is a report that in a skin irritation test (equivalent to OECD TG 404, GLP-compliant, n=12 (4 animals/2 periods)) with rabbits, after semi-occlusive application of this substance for 1, 2, 4, 8, 16 and 24 hours, no irritation was observed (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)). (5) There is a report that in a skin irritation test (equivalent to OECD TG 404, n=3/male and female) with rabbits, after 4-hour occlusive application of this substance, no irritation was observed (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) There is a report that in an eye irritation test (CFR 191.12 (equivalent to OECD TG 405), n=6) with rabbits, in which the undiluted liquid of this substance was applied, no eye irritation was observed at 24, 48 and 72 hours (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018), REACH registration dossier (Accessed Dec. 2018)). (2) There is a report that in an eye irritation test (equivalent to OECD TG 405, n=6) with rabbits, in which the undiluted liquid of this substance was applied, iritis was observed in 1/6 animals, but this resolved after 4 hours, and that conjunctival redness was observed in 3/6 animals, but this resolved in 24 hours, and swelling of the conjunctiva was observed in 1/6 animals, but this resolved in 24 hours, and no eye irritation was observed as a whole (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)). (3) There are descriptions that the vapor of this substance is transiently irritating to the cornea in humans but does not damage eyes (HSDB (2006)) and that the vapor of this substance has very low toxicity in humans and irritates the conjunctiva but does not affect the cornea (Patty (6th, 2012), HSDB (2006)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] In (1), no sensitisation is observed in humans, and as data supporting it, there are findings of humans in (2) and of animals in (3). Therefore, it was classified as "Not classified." Besides, based on new information, the category was changed from the previous classification. [Evidence Data] (1) There is a report that the undiluted liquid of this substance was applied to the skin of 100 subjects (finally 100 subjects out of 11 men and 97 women between 18 to 78 years of age) for 24 hours 9 times at 48 hour intervals (induction), the undiluted liquid of this substance was applied to different sites for 24 hours (challenge) after 14 days of cessation of exposure, and no skin sensitization was observed (SIAR (2011), Patty (6th, 2012), NICNAS IMAP (Accessed Dec. 2018), REACH registration dossier (Accessed Dec. 2018)). (2) There is a report that when the undiluted liquid of this substance was applied to the skin of 64 humans under a non-occlusive dressing for 48 hours, followed by removal of the patch, and then applied to the same site in the same manner a total of 10 times (induction), and the undiluted liquid of this substance was applied to a new site on the back (challenge) after 14 days of cessation of exposure, no skin sensitization was observed (SIDS Dossier (2011)). (3) There is a report that in a Maximization test (TSCATS OTS0572320, 10 animals/group) with guinea pigs, in which after intradermal injections of a 5% or 10% solution of this substance (solvent: 80% ethanol solution or 80% ethanol solution/Freund's complete adjuvant) at 3 sites, the undiluted liquid of this substance was occlusively applied for 48 hours (induction) and the undiluted liquid of this substance was occlusively applied for 24 hours 2 weeks after cessation of exposure (challenge), no skin sensitization was observed (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)).
5	Germ cell mutagenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Classification not possible" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for in vivo, it showed a negative result in an in-vivo chromosomal aberration test with rat bone marrow (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)). (2) As for in vitro, it showed all negative results in multiple bacterial reverse mutation tests (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)). (3) The results of chromosomal aberration tests and mouse lymphoma tests with cultured mammalian cells were negative (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] As for carcinogenicity, there are no available reports on humans. Based on (1) and (2), it was classified as "Classification not possible." [Evidence Data] (1) In a combined chronic toxicity/carcinogenicity study with rats (Fischer 344) exposed by inhalation (100-5,000 ppm) for up to 2 years, adenomas and carcinomas of the renal tubules were observed only in males but were judged to be due to alpha 2u-globulin-mediated mechanisms, and it was concluded that they do not apply to humans. In addition, since increased incidence of Leydig cell tumors in the testis was observed in all exposure groups at or above 100 ppm, but the tumors were also found in the control group, therefore, spontaneous tumors in the Fischer 344 strain were considered to be possibly promoted by exposure to this substance (SIAR (2011)). (2) There are no classification results by domestic and international organizations.
7	Reproductive toxicity	Classification not possible	- -	-	-	[Rationale for the Classification] In a two-generation study in (1), slight reproductive and developmental effects were observed in F1 and F2 pups at doses where general toxic effects were observed in parental animals. On the other hand, in a one-generation study in (2), in which in exposure up to the same highest dose, no general toxic effects were observed in maternal animals and no developmental effects were observed in F1 pups. However, due to not enough data on the fetotoxicity and developmental effects of pups, including teratogenicity, it was classified as "Classification not possible" due to lack of data. [Evidence Data] (1) In a two-generation reproductive toxicity study (OECD TG 416) with rats exposed by inhalation (100-5,000 ppm), no effects on fertility were observed at up to the high doses (5,000 ppm in F0, at or above 1,600 ppm in F1) where effects on the liver (pigmentation, chronic inflammation, hyperplasia of the bile duct) were observed in F0 male and F1 male and female parental animals. In pups, by administration of 5,000 ppm, decreased body weight gain in F1 males and females, decreased habituation ability and delayed acquisition of righting reflex in F2 females, and decreased auditory startle reflex in F2 males and females were observed (SIAR (2011)). (2) In a one-generation study (OECD TG 415) with rats exposed by inhalation (100-5,000 ppm), decreased body weight gain and food consumption were observed in F0 male paternal animals at the highest dose of 5,000 ppm, but no toxic effects were observed in maternal animals and also no clear developmental effects in F1 pups (SIAR (2011), Patty (6th, 2012), NICNAS IMAP (Accessed Dec. 2018)).
8	Specific target organ toxicity - Single exposure	Not classified	- -	-	-	[Rationale for the Classification] According to (1)-(3), since it can be judged that there are no effects due to exposure to this substance within the dose range of Category 2 through each route of the inhalation, dermal or oral routes, it was classified as "Not classified." Besides, the category was changed by using new information sources. [Evidence Data] (1) In a test in which rats were exposed by inhalation to the vapor of this substance for 4 hours, neither deaths nor symptoms manifested were observed in the lowest dose group (11,000 ppm (73.7 mg/L), exceeding the range of Category 2) (SIAR (2011)). (2) In a single dermal exposure test with rats, neither deaths nor symptoms manifested were observed at 2,000 mg/kg of the upper limit of Category 2. In addition, no treatment-related abnormal findings were observed in either of two single dermal application tests with rabbits at doses greater than the range of Category 2 (SIAR (2011)). (3) In all three single oral dose tests with rats, no treatment-related abnormal findings were observed at doses exceeding the range of Category 2 (SIAR (2011)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (genetic organs (men))	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] It was judged that the testis was the target organ base on (1) and (3), and that from (1), it was effects within the range of Category 1. In addition, findings in the respiratory organ (lung) were observed in (1) and (2), but because only slight changes in the nasal cavity were observed in the long-term exposure study in (3), the respiratory organs are not adopted as the target organ. From the above, it was classified in Category 1 (genetic organs (men)). Besides, the category was changed by using new information sources. [Evidence Data] (1) As a result of inhalation exposure of rats to the vapor of this substance for 13 weeks (6 hours/day, 5 days/week), subchronic or chronic interstitial pneumonia (female) and atrophy of seminiferous tubules of the testis were observed at 21 ppm (0.14 mg/L, converted guidance value: 0.10 mg/L) within the range of Category 1 (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)). (2) As a result of inhalation exposure of rats to the vapor of this substance for 4 weeks (6 hours/day, 5 days/week), slight inflammation of the lungs at or above 0.95 mg/L (converted guidance value: 0.21 mg/L, within the range of Category 2) and effects on the liver (increased liver weight, hepatocytes hypertrophy, increased pigmentation of the bile duct (59.26 mg/L)) at or above 12.75 mg/L (converted guidance value: 2.83 mg/L, exceeding the range of Category 2) were observed (SIAR (2011), NICNAS IMAP (Accessed Dec. 2018)). (3) As a result of inhalation exposure of rats to the vapor of this substance for one or 2 years (whole-body exposure, concentration 100-5,000 ppm), the target organs were thought to be the kidney (male), nasal cavity and testis (increased weight and increased incidence of Leydig cell tumors), and as for the kidney among these organs, it was concluded that nephropathy is from the alpha 2u-globulin mechanism (male rat specific finding) and not applicable to humans (SIAR (2011)). The changes in the nasal cavity (increased eosinophilic inclusion bodies in the olfactory epithelium) were observed from 100 ppm in females in the one year exposure group (0.67 mg/L, within the range of Category 2) (SIDS Dossier (2011)), but it was considered as an effect due to irritation of this substance and aging in mice (SIDS Dossier (2011)) (SIAR (2011)). [Reference Data, etc.] (4) In a 28-day test with rats dosed by gavage (up to 640 mg/kg/day or up to 1,500 mg/kg/day) and a 28-day dermal application test with rats (up to 1,000 mg/kg/day), no finding indicating target organ toxicity was obtained within the range of Category 2 (NICNAS IMAP (Accessed Dec. 2018), Patty (6th, 2012), SIAR (2011)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.46 mg/L for fish (Oncorhynchus mykiss) (OECD SIDS: 2011).
11	Hazardous to the aquatic environment (Long-term)	Category 1	Warning	H410	P273 P391 P501	If chronic toxicity data are used, then it is classified in Category 1 due to being not rapidly degradable and 21-day NOEC (reproduction inhibition) = 0.08 mg/L for crustacea (Daphnia magna) (OECD SIDS: 2011). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 1 due to being not rapidly degradable and 96-hour LC50 = 0.46 mg/L for fish (Oncorhynchus mykiss) (OECD SIDS: 2011). From the above results, it was classified in Category 1.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	No data available.

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.

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