NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	27605-76-1
Chemical Name	3-Allyloxy-1,2-benzoisothiazole 1,1-dioxide; Probenazole
Substance ID	R02-A-040-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	Classification not possible	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine), which is chemically bonded to an element (S) other than carbon or hydrogen. However, the classification is not possible due to no data.
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	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" (Category 5 in UN GHS classification) from (1) - (3). [Evidence Data] (1) LD50 for rats (males): 2,160 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)) (2) LD50 for rats (females): 2,310 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)) (3) LD50 for rats: 2,030 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 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: > 5,000 mg/kg (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 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)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) LC50 for rats (4 hours): > 5.03 mg/L (GLP) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 3), no irritation was seen when 0.1 mL of 10, 30 and 50% suspensions of this substance were applied to the back skin (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). [Reference Data, etc.] (2) It is reported that in an acute dermal toxicity test with rats (n = 20) (7-day observation, dose: 5,000 mg/kg), slight erythema was observed in the application sites but disappeared after 2 days (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
3	Serious eye damage/eye irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 3), after 1, 10, 30, and 50% suspensions of this substance were applied, no effects were observed on the eyelids, conjunctiva, cornea, or corneal reflex (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. Besides, a Buehler test was reported to be positive in (1), which was not used for classification due to a small number of test animals and because a positive rate was high in the negative control group. [Reference Data, etc.] (1) It is reported that in a Buehler test with guinea pigs (n = 10) (topical administration: 1% suspension), a positive was all 100% at 6, 24, 48, 72 hours after challenge and 30%, 60%, 50%, 60% at 6, 24, 48, 72 hours after challenge in the negative control group (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) In a micronucleus test using the bone marrow cells of mice (GLP, single oral dose), negative results were reported (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) In a bacterial reverse mutation test (GLP), negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (3) In a chromosomal aberration test (GLP) with the lung cells derived from Chinese hamsters, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (4) In a chromosomal aberration test (GLP) with the human lymphocyte cultures, negative results were obtained (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
6	Carcinogenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) In a 2-year chronic toxicity study with rats (dosed by feeding), at dosages up to 1,000 ppm at which weight gain inhibition was observed, neoplastic lesions, of which incidence increased in relation to the administration of the test substance administration, were not observed, and carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (2) In a 2-year chronic toxicity study with mice (dosed by feeding), at dosages up to 1,000 ppm at which profound toxic effects such as weight gain inhibition, a decrease in food intake, etc. were observed, neoplastic lesions, of which incidence increased in relation to the administration of the test substance administration, were not observed, and carcinogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2. [Evidence Data] (1) In a developmental toxicity study with rabbits dosed by gavage (GLP, days 6-18 of gestation), at 32 mg/kg/day, weight gain inhibition, a decrease in food intake, and miscarriage (1/17 cases) were observed in parental animals; and high values of embryonic/fetal death rates were observed in offspring. It was reported that teratogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). [Reference Data] (2) In a two-generation reproduction toxicity study with rats dosed by feeding (GLP), at 800 ppm, weight gain inhibition and a decrease in food intake (P and F1 male/female), and a decrease in the number of implantation (F1 female) were observed in parental animals; and a decrease in the number of births, weight gain inhibition (F1 and F2 male/female), preputial separation delay (F1 male), and vaginal opening delay (F1 female) were observed in offspring. It was reported that the delays of preputial separation and vaginal opening, and the decrease in the number of implantation in F1 were considered to be the secondary effects of the physical/nutritional status worsened by the decrease in food intake and the weight gain inhibition that were observed in P parental animals, and no effects on reproductive ability were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)). (3) It was reported that in a two-generation reproduction toxicity study with mice dosed by feeding, no effects on reproductive ability were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (4) It was reported that in a developmental toxicity study with rats dosed by gavage (GLP, days 7-17 of gestation), at 200 mg/kg/day, weight gain inhibition, a decrease in food intake, a decrease in placental weight, etc. were observed in parental animals; and low body weight, delayed ossification, and thymic remnant in the neck were observed in offspring, but teratogenicity was not observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2017)).
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	[Rationale for the Classification] Based on (1) to (4), the dosage for appearance of symptoms was not known (dead animal at or above 1,750 mg/kg BW (male), and dead animal at or above 1,500 mg/kg BW (female)), and classification was not possible due to lack of data. [Evidence Data] (1) It was reported that in an acute oral toxicity test with rats, a decrease in locomotor activity, depressed state, a decrease in body weight, piloerection, etc. were observed (the dosage for the appearance of the symptoms is not known) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (2) It was reported that in an acute oral toxicity test with rats, generalized tremors were observed in 24 hours after the administration (the dosage for the appearance of the symptom is not known) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (3) It was reported that in an acute oral toxicity test with mice, a decrease in locomotor activity, depressed state, a decrease in body weight, piloerection, etc. were observed (the dosage for the appearance of the symptoms is not known) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (4) It was reported that in an acute oral toxicity test with mice, ataxia and drunken gait were observed (the dosage for the appearance of the symptoms is not known) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). [Reference Data, etc.] (5) It was reported that in an acute dermal toxicity test with rats, at 5,000 mg/kg (in the range corresponding to "Not classified"), mild reddening in the application portion was observed (it disappeared in 2 days) (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (6) It was reported that in an acute inhalation (dust, mist) exposure test with rats (GLP, 4 hours), at 5.03 mg/L (in the range corresponding to "Not classified"), a decrease in locomotor activity, reddening in the nose, etc. were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system, liver)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1) to (5), clear effects were observed in the liver and the blood system within the dosage range for Category 2, it was classified in Category 2 (blood system, liver). [Evidence Data] (1) It was reported that in a 90-day oral toxicity test with rats dosed by feeding (GLP), at or above 300 ppm in male (19.8 mg/kg/day (male), 21.8 mg/kg/day (female), within the range for Category 2), and at or above 1,000 ppm in female (66.94 mg/kg/day (male), 72.97 mg/kg/day (female), within the range for Category 2), effects on the blood (a decrease in hematocrit (Ht)/increases in MCHC and white blood cell (WBC) count, male: decreases in red blood cell (RBC) count and eosinophil ratio/increases in MCH and neutrophil ratio/APTT shortening; female: a decrease in fibrinogen), effects on the liver (an increase in relative weight/an increase in ALP, male: increases in absolute weight/hepatocyte vacuolation), etc. were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (2) It was reported that in an subacute toxicity test with dogs (GLP), at 50 mg/kg/day (within the range for Category 2), weight gain inhibition, loose/watery stool, etc. were observed in males and females, and effects on the blood (male: increases in reticulocyte ratio/WBC, a decrease in lymphocyte ratio), on the liver (increases in absolute/relative weight, increases in AST/ALT/ALP, etc., liver fattening, and pigmentation of Kupffer cells), on the kidney (tubular vacuolization), etc., and also thymic atrophy and spleen follicle atrophy were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (3) It was reported that in a 1-year oral toxicity test with dogs (GLP), at 5 mg/kg/day (within the range for Category 1), effects on the liver (microgranuloma, female: hepatic glycogen accumulation/cellular infiltration) were observed; and at 25 mg/kg/day (within the range for Category 2), effects on the liver (increases in absolute/relative weight/an increase in ALP, male: hepatic glycogen accumulation/pigmentation of Kupffer cells/cellular infiltration/extramedullary hematopoiesis), and abnormalities in urinalysis (male: yellow-brown urine/bilirubinuria, female: uric blood/protein) were observed, and extramedullary hematopoiesis was also observed in males (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (4) It was reported that in a 2-year oral toxicity test with rats dosed by feeding, at 500 ppm in males (22 mg/kg/day (male), 27 mg/kg/day (female), within the range for Category 2), and at 1,000 ppm in females (44 mg/kg/day (male), 55 mg/kg/day (female), within the range for Category 2), effects on the liver (foamy hepatocytes, male: hepatocyte vacuolization), and pancreatic acinar cell atrophy were observed (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 2018)). (5) It was reported that in a 2-year oral toxicity test with mice dosed by feeding, at 500 ppm (76 mg/kg/day (male), 84 mg/kg/day (female), within the range for Category 2), poor physical statuses (paleness of the forelimbs and ear, subnormal temperature, circling, piloerection, wasting, lusterless fur, inactivity, etc.), and an increase in ALP were observed in males and females, and calcification in the renal cortical border was observed in males (Risk Assessment Report (Pesticides) (Food Safety Commission of Japan, 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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