Item | Information |
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CAS RN | 8018-01-7 |
Chemical Name | Complex compounds of manganese N,N'-ethylenebis(dithiocarbamate) and zinc N,N'-ethylenebis(dithiocarbamate) |
Substance ID | R03-C-057-MHLW, MOE |
Classification year (FY) | FY2021 |
Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE) |
New/Revised | Revised |
Classification result in other fiscal year | FY2006 |
Download of Excel format | Excel file |
Item | Information |
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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) | MHLW Website (in Japanese Only) |
Model SDS by MHLW (External link) | MHLW Website (in Japanese Only) |
OECD/eChemPortal (External link) | eChemPortal |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
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1 | Explosives | - |
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2 | Flammable gases | - |
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3 | Aerosols | - |
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4 | Oxidizing gases | - |
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5 | Gases under pressure | - |
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- | - | - |
6 | Flammable liquids | - |
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- | - | - |
7 | Flammable solids | - |
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- | - | - |
8 | Self-reactive substances and mixtures | - |
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9 | Pyrophoric liquids | - |
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10 | Pyrophoric solids | - |
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11 | Self-heating substances and mixtures | - |
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12 | Substances and mixtures which, in contact with water, emit flammable gases | - |
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13 | Oxidizing liquids | - |
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14 | Oxidizing solids | - |
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15 | Organic peroxides | - |
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16 | Corrosive to metals | - |
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17 | Desensitized explosives | - |
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- | - | - |
Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
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1 | Acute toxicity (Oral) | - |
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- | - | - |
1 | Acute toxicity (Dermal) | - |
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- | - | - |
1 | Acute toxicity (Inhalation: Gases) | - |
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1 | Acute toxicity (Inhalation: Vapours) | - |
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1 | Acute toxicity (Inhalation: Dusts and mists) | - |
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2 | Skin corrosion/irritation | - |
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3 | Serious eye damage/eye irritation | - |
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4 | Respiratory sensitization | - |
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4 | Skin sensitization | - |
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5 | Germ cell mutagenicity | - |
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6 | Carcinogenicity | - |
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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)). |
8 | Specific target organ toxicity - Single exposure | - |
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9 | Specific target organ toxicity - Repeated exposure | - |
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10 | Aspiration hazard | - |
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Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
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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) |
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) |
12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. |
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