NITE - Chemical Management Field

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

GENERAL INFORMATION

Item	Information
CAS RN	8018-01-7
Chemical Name	Complex compounds of manganese N,N'-ethylenebis(dithiocarbamate) and zinc N,N'-ethylenebis(dithiocarbamate)
Substance ID	m-nite-8018-01-7_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)	- -	-	-	Containing no chemical groups with explosive properties	FY2006	GHS Classification Manual （10 Feb, 2006）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Classified as "solid" according to GHS definition	FY2006	GHS Classification Manual （10 Feb, 2006）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products	FY2006	GHS Classification Manual （10 Feb, 2006）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Classified as "solid" according to GHS definition	FY2006	GHS Classification Manual （10 Feb, 2006）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Classified as "solid" according to GHS definition	FY2006	GHS Classification Manual （10 Feb, 2006）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Classified as "solid" according to GHS definition	FY2006	GHS Classification Manual （10 Feb, 2006）
7	Flammable solids	Classification not possible	- -	-	-	Classification not possible due to lack of data, though classified as flammable according to ICSC (2003)	FY2006	GHS Classification Manual （10 Feb, 2006）
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	Containing no chemical groups with explosive or self-reactive properties	FY2006	GHS Classification Manual （10 Feb, 2006）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Classified as "solid" according to GHS definition	FY2006	GHS Classification Manual （10 Feb, 2006）
10	Pyrophoric solids	Classification not possible	- -	-	-	Classification not possible due to lack of data	FY2006	GHS Classification Manual （10 Feb, 2006）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	Classification not possible due to lack of data	FY2006	GHS Classification Manual （10 Feb, 2006）
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	Stable to water (water solubility: 6 plus or minus 3ppm, Agricultural Chemical Registration Data)	FY2006	GHS Classification Manual （10 Feb, 2006）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Classified as "solid" according to GHS definition	FY2006	GHS Classification Manual （10 Feb, 2006）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	Organic compounds containing chlorine, fluorine and oxygen	FY2006	GHS Classification Manual （10 Feb, 2006）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no "-O-O-" structure	FY2006	GHS Classification Manual （10 Feb, 2006）
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances with melting point of >55degC are not available (melting point: thermally decomposes at 190degC (Agricultural Chemical Registration Data)).	FY2006	GHS Classification Manual （10 Feb, 2006）
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)	Not classified	- -	-	-	Based on the rat LD50 (oral route) value of >5,000mg/kg (Agricultural Chemical Registration Data (1993)).	FY2006	GHS Classification Manual （10 Feb, 2006）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Based on the rat LD50 (dermal route) value of >5,000mg/kg (Agricultural Chemical Registration Data (1987)).	FY2006	GHS Classification Manual （10 Feb, 2006）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Due to the fact that the substance is a solid according to the GHS criteria and inhalation of its gas is not expected.	FY2006	GHS Classification Manual （10 Feb, 2006）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available	FY2006	GHS Classification Manual （10 Feb, 2006）
1	Acute toxicity (Inhalation: Dusts and mists)	Not classified	- -	-	-	Based on the absence of mortality at the highest dose of 5.08mg/L in rat inhalation studies (Agricultural Chemical Registration Data (1993)).	FY2006	GHS Classification Manual （10 Feb, 2006）
2	Skin corrosion/irritation	Not classified	- -	-	-	Based on test data from rabbit skin corrosivity studies (Agricultural Chemical Registration Data (1987)): "Erythematous responses were noted immediately after the application, but the affected animals exhibited scores of 0 at 72 hours."	FY2006	GHS Classification Manual （10 Feb, 2006）
3	Serious eye damage/eye irritation	Category 2B	- Warning	H320	P305+P351+P338 P337+P313 P264	Based on test data from rabbit eye irritation studies (Agricultural Chemical Registration Data (1993)): "Caused mild irritation of the eye, with effects resolving within 7 days."	FY2006	GHS Classification Manual （10 Feb, 2006）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available	FY2006	GHS Classification Manual （10 Feb, 2006）
4	Skin sensitization	Category 1	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	Based on positive results in guinea pig skin sensitization studies using the Buehler and Maximization methods (Agricultural Chemical Registration Data (1987, 1993)).	FY2006	GHS Classification Manual （10 Feb, 2006）
5	Germ cell mutagenicity	Not classified	- -	-	-	Based on negative data in in vitro studies (reverse mutation tests, chromosome aberration tests and DNA repair tests) and in vivo studies (mouse micronucleus tests and rat chromosome aberration tests) (Agricultural Chemical Registration Data (1987, 1993)).	FY2006	GHS Classification Manual （10 Feb, 2006）
6	Carcinogenicity	Not classified	- -	-	-	There was no evidence of treatment-related incidence of tumor formation observed in 2-year (rats) and 18-month (mice) carcinogenicity studies (Agricultural Chemical Registration Data (1993)).	FY2006	GHS Classification Manual （10 Feb, 2006）
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1), an increase in the incidence of malformations was observed at a dose at which general toxicity effects were observed in dams. In addition, based on (2) to (4), as for the main metabolite (ethylene thiourea) of this substance, an increase in the incidence of malformations was observed in a developmental toxicity study with rats. Accordingly, effects of this substance on offspring in (1) could not be considered to be secondary effects of the effects on dams. Therefore, it was classified in Category 1B. [Evidence Data] (1) In a developmental toxicity study with female rats dosed by gavage (compliant with EPA OPPTS 870.3700, 2 to 512 mg/kg/day, days 6 to 15 of gestation), reduced body weight gain and food consumption were observed in dams at or above 128 mg/kg/day, and 3/22 animals which had systemic symptoms (such as lethargy, scruffy coat, diarrhea, soft feces, bloody vaginal discharge) were killed in extremis, and complete embryo resorption was observed in live animals (6/19 animals) at the highest dose (512 mg/kg/day). It was reported that a decrease in the number of live fetuses, a decrease in fetal weight, and an increase in the incidence of malformations (meningoencephalocele/exencephaly, dilated brain ventricles, cleft palate, kinked/shortened tail) were observed in fetuses of the highest-dose group (CLH Report (2017), ECHA RAC Opinion (2019)). (2) It was reported that, in a developmental toxicity study with rats dosed by gavage (OECD TG 414, GLP, 2.5 to 30 mg/kg/day, days 6 to 19 of gestation) using ethylene thiourea (ETU, CAS RN 96-45-7), which is the main metabolite of this substance, as the test substance, no maternal toxicity was observed up to the highest dose (30 mg/kg/day), but in fetuses, malformations (hydrocephaly) were observed in 2/24 animals at 15 mg/kg/day, and lower body weight and malformations (malformed tail, meningocele, hydrocephaly, malrotated limb, limb hyperextension, rib and vertebral anomalies) were observed at the highest dose (30 mg/kg/day) (CLH Report (2017), ECHA RAC Opinion (2019)). (3) Ethylene thiourea (ETU, CAS RN 96-45-7) is a developmental toxicant (EU CLP classification result: Repr. 1B) which causes malformations in rats at a dose at which maternal toxicity is absent. Approximately 7% of this substance is converted to ETU in experimental animals. It was reported that as the evidence suggesting that the malformations (mainly of head and neck) seen in the rat with this substance are due to its main metabolite, ETU, a developmental toxicity study with rats using ETU (including measurements of plasma levels of ETU) has been conducted to demonstrate that the fetal malformations caused by this substance in the rat are due to the production of a teratogenic dose of ETU (CLH Report (2017), ECHA RAC Opinion (2019)). (4) ETU was classified in Category 1B in Japan (GHS classification result in FY2013). [Reference Data, etc.] (5) In a two-generation reproduction toxicity study with rats dosed by feeding (OECD TG 416, GLP, 30 to 1,200 ppm (up to approx. 70 mg/kg/day)), in P1 and P2 (F0 and F1) parent animals, at or above 120 ppm, effects on the kidney (brown globular pigment within the lumen of proximal tubule) were observed in males and females, and an increase in relative liver weight was observed in P2 males; and at 1,200 ppm, systemic toxicity effects such as effects on the thyroid (diffuse hyperplasia of follicular cells, nodular follicular cell hyperplasia, and follicular cell adenoma (males only), pituitary (such as hypertrophy/vacuolation of cells in the adenohypophysis) were observed in P1 and P2 males and females, but no reproduction toxicity effects were observed in either P1 or P2 generations. It was also reported that no developmental effects related to administration were observed in F1 or F2 offspring (REACH registration dossier (Accessed Nov. 2021)). (6) It was reported that, in a developmental toxicity study (OECD TG 414, GLP) with female rats dosed by gavage (10 to 360 mg/kg/day) on days 6 to 15 of gestation, incomplete ossification of the interparietal bone, non-ossification of the thoracic centra, and an increase in the incidence of large anterior fontanelle were observed in fetuses at a high dose (360 mg/kg/day) at which death (1/25 animals), reduced body weight gain and food consumption, staggering gait, and slight paralysis of the hindlimbs (5/25 animals) were observed in dams (REACH registration dossier (Accessed Nov. 2021)). (7) It was reported that, in a developmental toxicity study (OECD TG 414, GLP) with female rats dosed by gavage (10 to 500 mg/kg/day) on days 6 to 15 of gestation, no maternal toxicity was observed up to the highest dose, but macroscopic pathology in the lung (congestion/hyperemia), liver (congestion/mottling), and kidney (patchy congestion/congestion), and dumbbell shaped thoracic centra were observed in fetuses at or above the mid-dose (225 mg/kg/day) (CLH Report (2017), ECHA RAC Opinion (2019)). (8) It was reported that, in two developmental toxicity studies with pregnant rabbits dosed by gavage (10 to 80 mg/kg/day (days 7 to 19 of gestation), 5 to 100 mg/kg/day (days 6 to 18 of gestation)), developmental effects (abortion, an increase in post-implantation loss) were observed at the highest dose at which maternal toxicity (death (2/20 animals), reduced body weight gain and food consumption) was observed (CLH Report (2017), ECHA RAC Opinion (2019)). (9) It was reported that, in two developmental neurotoxicity studies with pregnant rats dosed by feeding (5 to 60 mg/kg/day (from day 6 of gestation to postnatal day 21 or 28), 5 to 30 mg/kg/day (from day 6 of gestation to postnatal day 21)), no developmental neurotoxicity was observed up to the highest dose at which reduced body weight gain and effects on the thyroid (follicular cell hypertrophy) were observed in dams (CLH Report (2017), ECHA RAC Opinion (2019)). (10) In the EU classification, this substance was classified as Repr. 1B (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	Classification not possible	- -	-	-	No symptoms or signs referable to specific target organs were observed at dose levels within the guidance value ranges for Category 2 in the available single dose toxicity studies in rats and mice (Agricultural Chemical Registration Data (1993)).	FY2006	GHS Classification Manual （10 Feb, 2006）
9	Specific target organ toxicity - Repeated exposure	Category 2 (nervous system, thyroid, liver, adrenal gland)	Warning	H373	P260 P314 P501	Based on the evidence from animal studies including vacuolization/phagocytosis of myelin sheath, Schwann cell proliferation, increased thyroid weights, proliferation of follicular epithelium of the thyroid gland, hepatocellular hypertrophy, hypertrophy of basophilic cells of anterior lobe of hypophysis, and hypertrophy of adrenal cortical glomerulosa cells (Agricultural Chemical Registration Data (1993, 2004)). These effects were observed at dosing levels within the guidance value ranges for Category 2.	FY2006	GHS Classification Manual （10 Feb, 2006）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available	FY2006	GHS Classification Manual （10 Feb, 2006）

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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 72-hour ErC50 = 0.0126 mg a.i./L for algae (Raphidocelis subcapitata) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2017). (a.i.: active ingredient)	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
11	Hazardous to the aquatic environment Long term (Chronic)	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 (BIOWIN) and 35-day NOAEC = 0.00219 mg/L for fish (Pimephales promelas) (EPA Pesticides RED, 2005, OPP Pesticide Ecotoxicity Database). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained (algae), then it is classified in Category 1 due to being not rapidly degradable and 72-hour ErC50 = 0.0126 mg a.i./L for algae (Raphidocelis subcapitata) (Document for registration standards for agricultural chemicals set by the Minister of Environment to prevent harm to animals and plants in areas of public waters, 2017). From the above results, it was classified in Category 1. (a.i.: active ingredient)	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.	FY2021	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))

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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