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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	64359-81-5
Chemical Name	4,5-dichloro-2-octyl-2H-isothiazol-3-one
Substance ID	R02-A-014-METI
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)
New/Revised	New
Classification result in other fiscal year
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
UN GHS document (External link)	UN GHS document
Definitions/Abbreviations (Excel file)	Definitions/Abbreviations
Model Label by MHLW (External link)
Model SDS by MHLW (External link)
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Classification not possible	- -	-	-	No data available.
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with self-reactive properties (ethylene group) present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not available.
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).
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule.
16	Corrosive to metals	Classification not possible	- -	-	-	It is a solid with a melting point of 55 deg C or lower, but the classification is not possible due to no data.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] It was classified in Category 4 from (1) - (3). [Evidence Data] (1) LD50 for rats: 1,636 mg/kg (OECD TG 401) (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)) (2) LD50 for rats: between 500-2,000 mg/kg (OECD TG 423) (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)) (3) LD50 for mice: 567 mg/kg (OECD TG 401) (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (OECD TG 402) (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)) [Reference Data, etc.] (2) LD50 for rabbits: > 652 mg/kg (OECD TG 402, purity: 32.6% (medium: xylene)) (ECHA RAC Opinion (2018))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Category 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1), (2). [Evidence Data] (1) LC50 for rats (4 hours): 0.26 mg/L (males: 0.21 mg/L, females: 0.34 mg/L, OECD TG 403) (ECHA RAC Opinion (2018)) (2) LC50 for rats (4 hours): 0.164 mg/L (OECD TG 403) (ECHA RAC Opinion (2018))
2	Skin corrosion/irritation	Category 1	Danger	H314	P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501	[Rationale for the Classification] It was classified in Category 1 from (1) - (4). [Evidence Data] (1) It is reported that in a human repeated insult patch test (HRIPT) in 34 persons, barely perceptible to moderate irritation reactions were observed in 16 during the induction phase with a 0.025% solution of this substance (ECHA RAC Opinion (2018)). (2) In a skin irritation test with rabbits (n = 3) (OECD TG 404, 4-hour application, 14-day observation), all the animals showed slight to severe erythema/edema throughout 14 days, and effects were irreversible. Destruction of all layers of the skin was estimated after 4-hour application of this substance (erythema/eschar score: 3.3/2/1.7, edema score: 2.7/2/2) (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)). (3) In a skin irritation test with a rabbit (n = 1) (OECD TG 404, 4-hour application, 14-day observation), the mean score at 24/48/72 hours was 4.0 for erythema and 3.3 for edema. Skin irritation indicative of corrosivity (concave eschar) was seen within 48 hours, and corrosive findings (ulcer /erosion) were observed after 14 days. Skin reactions were considered as corrosive (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)). (4) In a skin irritation test with rabbits (n = 6) (OECD TG 404, 4-hour application, 14-day observation), moderate to severe erythema/edema was seen after 1 hour. The mean score at 24/48/72 hours was 4.0 for erythema and 3.9 for edema. At 14 days, there was no edema, but slight to severe erythema, eschar, areas without hair growth, and whitened areas, and scar formation was observed in 5 of 6 animals. Skin reactions were considered as corrosive (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] It was classified in Category 1 from (1). [Evidence Data] (1) It was classified in Category 1 in skin corrosion/ irritation.
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1A	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1A from (1) - (5). [Evidence Data] (1) It is reported that in a patch test in 34 persons, after induction by 9-time applications of 0.2 mL of 0.025% and 0.035% solutions over 3 weeks followed by challenge by 24-hour application of 0.01%, 0.025%, and 0.035% solutions 2 weeks later, a positive rate was 12% (3/34) for a 0.025% solution and 41% (14/34) for a 0.035% solution. After 6 months, 8 persons who tested positive to a 0.035% solution were re-challenged by 24-hour occlusive application of a 0.025% solution, and three had positive reactions (ECHA RAC Opinion (2018), ACIS (formerly, NICNAS IMAP) (2018)). (2) It is reported that in a textile processing plant, a 30% solution of this substance (xylene) was mixed in a finishing agent as a biocide, and 8 out of 19 workers developed itchy reddish eruptions on the exposed areas of the skin about 3 weeks later. After direct application of a finishing agent containing 0.06% of this substance to the upper arms (2*2 cm2) in 6 of them, strong positive reactions were observed in 5 except one who ingested corticoids 2 days before (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)). (3) It is reported that in a local lymph node assay (LLNA) with mice (n = 4/group) (OECD TG 429), stimulation index (SI values) was 0.8 (0.005%), 1.1 (0.01%), 11.6 (0.1%), 25.7 (0.25%), 27.0 (0.5%), and the EC3 value was calculated as 0.03% (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)). (4) It is reported that in a maximization test with guinea pigs (n = 20) (OECD TG 406, intradermal administration: 5% solution), a positive rate was 60% (12/20), 45% (9/20) at 24, 48 hours after challenge (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)). (5) It is reported that in a maximization test with guinea pigs (n = 20) (OECD TG 406, intradermal administration: 0.01%, 0.02%, 0.03% solution), a positive rate at 24, 48 hours after challenge was 75% (12/20), 45% (9/20) when a 0.01% solution was administered, 95% (19/20) for both when a 0.02% solution was administered, and 100% (20/20) for both when a 0.03% solution was administered (ECHA RAC Opinion (2018), AICIS (formerly, NICNAS IMAP) (2018)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (6), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using bone marrow from mice (OECD TG 474), negative results were reported (ECHA RAC Opinion (2018)). (2) In a chromosomal aberration test using bone marrow from mice (OECD TG 475), negative results were reported (ECHA RAC Opinion (2018)). (3) In an unscheduled DNA synthesis (UDS) test using liver from rats (OECD TG 486), negative results were reported (ECHA RAC Opinion (2018)). (4) In a bacterial reverse mutation test (OECD TG 471), negative results were reported (ECHA RAC Opinion (2018)). (5) In an in vitro chromosomal aberration test (OECD TG 473), negative results were reported (ECHA RAC Opinion (2018)). (6) In a gene mutation test (OECD TG 476), negative results were reported (ECHA RAC Opinion (2018)).
6	Carcinogenicity	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1B. The lesions in the eyes observed in pups in (4) were the effects at the dose at which general toxicity appeared in parental animals, but the retinal abnormalities were considered as irreversible and marked dysfunctions, and the importance of the effects was taken into account. [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG416, GLP, for 10 weeks before mating and until sacrifice of parents), at 400 ppm at which no general toxicity was observed in F0 parental animals, a decrease in spleen weight, a delay in vaginal opening and a delay in preputial separation were observed in F1 offsprings and a decrease in thymus weight was observed in F2 offsprings (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (2) In a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG416, GLP, for 10 weeks before mating and up to two weeks of mating period; for females, gestation and lactation periods in addition), at 350 ppm, lower final body weight was observed in parental animals, while only an decrease in absolute and relative spleen weight was observed in F2 offsprings. At 100 ppm at which no general toxicity appeared in parental animals, only an increase in relative brain weight was observed in F2 offsprings (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (3) It was reported that in a developmental toxicity study with rats dosed by gavage (OECD TG414, GLP, gestational days 6 to 15), no developmental toxicity was observed (ECHA RAC Opinion (2018)). (4) It was reported that in a developmental toxicity study with rabbits dosed by feeding (OECD TG414, day 6 to 28 of gestation), at 44 mg/kg/day, one parental animal died, and reduced body weight gain, decreased food consumption, and delivery of pups with lesions in the eyes (3 cases) were observed in parental animals, and retinal abnormalities (retina, choroid and sclera detachments) were observed in the pups (3 litters, 4 fetuses) (ECHA RAC Opinion (2018)).
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs), Category 3 (narcotic effects)	Danger Warning	H370 H336	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] Based on (1) and (3), narcotic effects were observed in the oral and inhalation routes, and based on (2) and (3), effects on respiratory organs in the dosing range of Category 1 were observed in the inhalation route. Therefore, it was classified in Category 1 (respiratory organs) and Category 3 (narcotic effects). [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats (OECD TG423), lethargy, abdominal breathing and nostril discharge were observed at and above 200 mg/kg (within the range of Category 1), toe walking and piloerection were observed at and above 500 mg/kg (within the range for Category 2) and gasping, salivation, diarrhea and pathological changes in the lung, liver, kidney and spleen were observed at 2000 mg/kg (within the range for Category 2) (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (2) In an acute inhalation (dust) toxicity test with rats (OECD TG403, for 4 hours), clinical signs of respiratory irritation (gasping, slight to severe rales), unkempt appearance, red stained eyes and muzzle, scant feces and yellow stained anogenital area were observed at 0.12 mg/L to 0.46 mg/L (within the range for Category 1). Additionally, it was reported that at necropsy after 14 days, slight to severe redness in lobes of the lungs and gas-filled stomachs were observed, and the deaths were presumed to be attributed to excessive secretion of this substance in the respiratory tract due to irritation/corrosivity (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (3) It was reported that in an acute inhalation (dust) toxicity test with rats (OECD TG403, for 4 hours), lethargy, tremors, abdominal breathing, gasping and nasal irritation were observed at 0.143 mg/L to 0.289 mg/L (within the range for Category 1), and vascular/inflammatory changes in the lungs were observed at necropsy (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1), respiratory symptoms due to irritation and alterations in tissues in the respiratory organs were observed in the concentration range of Category 1 in the inhalation route. Therefore, it was classified in Category 1 (respiratory organs). [Evidence Data] (1) It was reported that in a 90-day inhalation (dust) exposure test with rats (OECD TG413, 6 hours/day, 5 days/week, purity: 32.6% (vehicle: xylene)), rales, gasping and dyspnea were observed at 0.02 to 6.72 mg/m3 (converted guidance value: 0.000014 to 0.0048 mg/L/6 hours, within the range for Category 1) and inflammation, epithelial hyperplasia and goblet cell hyperplasia in the nasal cavity, larynx and lung were observed after the exposure at 0.63 to 6.72 mg/m3 (converted guidance value: 0.00045 to 0.0048 mg/L/6 hours, within the range for Category 1) (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). [Reference Data, etc.] (2) It was reported that in a 4-week repeated oral dose toxicity study with rats dosed by gavage, hyperplasia of the mucosal epithelium of the stomach and small intestine was observed at 100 mg/kg/day (converted guidance value: 31.1 mg/kg/day, within the range for Category 2), and the findings in the gastrointestinal tract were considered to be the direct effects of mucosal irritation by this substance (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (3) It was reported that in a repeated dose 90-day oral toxicity study with rats dosed by feeding (OECD TG408), irritative changes in the forestomach (from minimal hyperkeratosis and slight epithelial hyperplasia to erosion/ulceration with associated inflammation and edema of the submucosa) were observed at and above 1,000 ppm (60.7 mg/kg/day (males), 74.7 mg/kg/day (females)) and the findings were considered to be the direct effects of mucosal irritation by this substance (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (4) It was reported that in a repeated dose 90-day oral toxicity study with dogs dosed by feeding (OECD TG409), there were no findings by which target organs could be identified at up to 1,500 ppm (up to 47.5 mg/kg/day (males), up to 45.9 mg/kg/day (females), within the range for Category 2). Increased incidence and severity of thymic atrophy (females) were considered to be the secondary effects due to decreased body weight and food consumption (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (5) It was reported that in a repeated dose 90-day oral toxicity study with dogs dosed by feeding (OECD TG409), increased serum AST, ALT, GLT activities (mainly in males) were observed at 3,000 to 4,500 ppm (within the range for Category 2), but no histopathological changes were observed in the liver (ECHA RAC Opinion (2018)). (6) It was reported that in a repeated dose 28-day dermal toxicity study with rats (OECD TG410), dose-dependent local skin reactions (erythema, edema, wounds and beginning necrosis) were observed at 3 to 60 mg/kg/day (Top dose: 60 mg/kg/day from beginning to day 9, no administration on day 10 to 22, 30 mg/kg/day on day 23) (converted guidance value: 0.93 to 18.7 mg/kg/day, within the range for Category 1), and 6/20 males and 8/20 females died at the top dose (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)). (7) It was reported that in a repeated dose 21-day dermal toxicity study with rabbits (purity: 35% (vehicle: mixed xylene diluted in acetone)), slight skin irritation at 0.35 mg/kg/day (converted guidance value: 0.058 mg/kg/day, within the range for Category 1) and moderate to severe skin irritation at 1.75 mg/kg/day (converted guidance value: 0.29 mg/kg/day, within the range for Category 1) were observed, but no systemic effects were observed (ECHA RAC Opinion (2018), AICIS (previous NICNAS IMAP) (2018)).
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 Short term (Acute)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
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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