GHS Classification Result

Chemical Name:iprodione (ISO); 3-(3,5-dichlorophenyl)-2,4-dioxo-N-isopropylimidazolidine-1-carboxamide
CAS:36734-19-7

Result:
ID: 20A2274
Classifier: Ministry of Health, Labour and Welfare (MHLW), Ministry of the Environment (MOE)
Year Classified: FY2008
Reference Manual: GHS Classification Guidance by the Japanese Government (Sep, 2008)

PHYSICAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Explosives Not applicable - - - - There are no chemical groups associated with explosive properties present in the molecules.
2 Flammable gases (including chemically unstable gases) Not applicable - - - - Solid (GHS definition)
3 Aerosols Not applicable - - - - Not aerosol products.
4 Oxidizing gases Not applicable - - - - Solid (GHS definition)
5 Gases under pressure Not applicable - - - - Solid (GHS definition)
6 Flammable liquids Not applicable - - - - Solid (GHS definition)
7 Flammable solid Classification not possible - - - - No data available.
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 applicable - - - - Solid (GHS definition)
10 Pyrophoric solids Not classified - - - - Its autoignition point is higher than 70degC (autoignition point: ca. 150-200degC (1013 hPa), IUCLID (2000)).
11 Self-heating substances and mixtures Classification not possible - - - - Test methods applicable to solid (melting point <= 140degC) substances are not available. (melting point: 134degC, Ullmanns (E) (6th, 2003))
12 Substances and mixtures which, in contact with water, emit flammable gases 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 applicable - - - - Solid (GHS definition)
14 Oxidizing solids Not applicable - - - - Organic compounds containing chlorine and oxygen (but not fluorine), which are chemically bonded only to carbon or hydrogen.
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. Non-corrosive to metals (HSDB (2003)).

HEALTH HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Acute toxicity (Oral) Not classified - - - - Since its rat LD50 values documented are > 2000 (OECD TG 401) and 3700 mg/kg (JMPR (1992)), the substance was classified into "Not classified" using the JIS classification criteria (Category 5 or "Not classified" in the United Nations classification).
1 Acute toxicity (Dermal) Not classified - - - - Based on its rat LD50 of > 2000 mg/kg (EPA TG 81-2) (JMPR (1992)), the substance was classified into "Not classified" using the JIS classification criteria (Category 5 or "Not classified" in the United Nations classification).
1 Acute toxicity (Inhalation: Gases) Not applicable - - - - Solid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Classification not possible - - - - No data available.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible - - - - Its rat LC50 values documented are > 3.29 mg/L/4h (JMPR (1992)) and > 5.16 mg/L/4h (OECD TG 403) (IUCLID (2000)), which do not justify placing the substance into the "Not classified" category. It was instead classified into the "Classification not possible" category. Since test concentrations were > 3.29 and > 5.16 mg/L, which were higher than the saturated vapour pressure concentration of the test substance: 6.66E-008 mg/L, we concluded that the test was conducted in a dust state.
2 Skin corrosion/irritation Not classified - - - - Since the test using rabbits (US EPA Guidelines 81-5) found that the substance is not irritating (IUCLID (2000)), it was classified into "Not classified".
3 Serious eye damage/eye irritation Category 2B - Warning H320: Causes eye irritation P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P337+P313: If eye irritation persists: Get medical advice/attention.
P264: Wash ... thoroughly after handling.
Since the test using rabbits (US EPA Guidelines 81-4) found that the substance is slightly irritating (IUCLID (2000)), it was classified into Category 2B. It is documented that conjunctival irritation observed in this test diminished during the test period, and it healed completely 7 days after application.
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - In tests using guinea pigs, it was reported that the evidence for skin sensitization was not found (JMPR (1977)). Likewise, in a different test using guinea pigs (Buehler tests, US EPA Guidelines 81-6), the substance was found to be non-sensitizing (IUCLID (2000)). Despite these negative results reported, the substance was classified into "Classification not possible" because information provided in these tests is insufficient.
5 Germ cell mutagenicity Not classified - - - - Dominant lethal tests using mice that underwent oral administration (mixed diet) for 49 days (in vivo heritable mutagenicity tests using germ cells) resulted in negative outcome (JMPR (1992), IUCLID (2000)). Thus, the substance was classified into "Not classified". In vitro mutagenicity tests (Ames tests, mutation tests using E. coli, mutation tests using CHO cells, and chromosomal aberration tests) also gave negative results (JMPR (1992)).
6 Carcinogenicity Category 2 Warning H351: Suspected of causing cancer P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ...
In 52- and 104-week oral administration (mixed diet) tests using rats, incidence of interstitial-cell tumors of the testis increased. In 24-months oral administration (mixed diet) tests using rats, development of pituitary adenoma, adenocarcinoma, or fibroadenoma of the mammary gland were observed (JMPR (1995)). In 99-week oral administration (mixed diet) tests using mice, an increased incidence of benign or malignant liver tumors in both sexes, and an increased incidence of luteomas in the ovaries were observed. In 18-month oral administration (mixed diet) tests using mice, tumors observed were lymphosarcomas involving the spleen, lymph nodes and thymus (JMPR (1995). Furthermore, the substance is rated as Category 3 in the EU's carcinogenicity evaluations. All these reports considered, the substance was classified into Category 2.
7 Reproductive toxicity Category 2 Warning H361: Suspected of damaging fertility or the unborn child P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ...
In 2-generation tests using rats that underwent mixed diet administration, litter size decreased in animal groups treated with the highest dose (3000 ppm) that induced general toxicity (decrease in body weight or food consumption) in parental animals (JMPR (1992)). Moreover, in oral administration tests conducted using rats or rabbits during the oraganogenetic period, the number of implantation sites decreased in rat groups treated with the highest dose (400 mg/kg/day) that reduced body weight or food consumption of parental animals (JMPR (1992)); similarly, miscarriage and rates of postimplantation loss increased in rabbit groups treated with the highest dose (200 mg/kg/day) (JMPR (1992)). Based on these studies, the substance was classified into Category 2.
8 Specific target organ toxicity - Single exposure Category 2 (nervous system) Warning H371: May cause damage to organs (nervous system) P309+P311: IF exposed or if you feel unwell: Call a POISON CENTER or doctor/physician.
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P405: Store locked up.
P501: Dispose of contents/container to ...
In oral administration tests using rats, surviving animals treated at 2000 mg/kg or above comprised lethargy, decreased motor activity, prone posture, ataxia, unconsciousness, breathing irregularities, piloerection, ungroomed appearance, pigmented orbital secretion, hunched posture, thin body conformation, diarrhoea and reduced body temperature. At the doses of 900 or 1342 mg/kg, signs of lethargy, decreased motor activity, ataxia, and prone posture were observed (IUCLID (2000)). Based on these observations, the substance was classified into Category 2 (nervous system). In dermal administration tests using rabbits, no abnormalities were detected in 8 of the 10 animals treated with 2000 mg/kg based on visual inspection; one of the two remaining animals (it is noted that this animal got cut around the neck and in the mouth during the experiment) showed red staining on the skin around the mouth, and clear discharge on fur around the nares, distended abdomen, as well as distended small intestines, cecum and stomach with abnormal contents and vascularized stomach and cecum. However, it is noted that these observations are not clearly attributable to iprodione (IUCLID (2000)). Furthermore, in inhalation tests using rats, clinical signs were unspecific at the dose of 5.16 mg/L/4h and they were observed on the day of exposure and up to 2 days after the exposure; the signs observed include blepharospasm, periocular and perinasal wetness, periocular and perinasal encrustation, unkempt fur, and white powder on the fur (IUCLID (2000)). However, these signs developed at the doses higher than the guidance values.
9 Specific target organ toxicity - Repeated exposure Category 2 (hematopoietic system) Warning H373: May cause damage to organs through prolonged or repeated exposure (hematopoietic system) P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P314: Get medical advice/attention if you feel unwell.
P501: Dispose of contents/container to ...
The substance was classified into Category 2 (hematopoietic system) based on 52-week oral administration (mixed diet) tests using rats, in which incidence of extramedullary haematopoiesis and haemosiderosis increased in the spleens of female rats at 1600 ppm (conversion value: 80 mg/kg bw /day) (JMPR (1995)). In 99-week oral administration (mixed diet) tests using mice, the kidney with irregular cortical scarring and altered shape were observed at a higher incidence in females at 4000 ppm; in the liver, an increased incidence of enlarged eosinophilic and fat-containing hepatocytes was observed in animals of each sex at the highest dose; and centrilobular hepatocyte enlargement was observed in female rats treated with 800 ppm (conversion value: 120 mg/kg bw /day) and both sexes treated with 4000 ppm. Pigmented macrophages and centrilobular hepatocyte vacuolation were found in males at 4000 ppm; and haemosiderosis in the spleen, amyloidosis, and cortical scarring in the kidneys were reported in female mice at the highest dose (JMPR (1995). In 28-day oral administration (mixed diet) tests, exposure to 6000 ppm or higher was associated with ataxia and lethargy; livers had a stippled appearance on gross examination, and the incidence of hepatocyte vacuolation and focal eosinophilic degeneration was increased at 6000 ppm or higher. At 15000 ppm, granulomatous inflammation (possibly in response to a foreign body) was observed in the heart, liver, and kidney (JMPR (1992). In 4-week oral administration (mixed diet) using mice, depression and ataxia were observed at 6000 ppm or higher. Gross necropsy revealed white foci in the liver of mice receiving 1900 ppm (male: 366 mg/kg bw /day; female: 439 mg/kg bw /day) and higher, a stippled appearance of the liver at 6000 ppm and higher, and liver enlargement at 9500 and 15000 ppm. White foci and granulomatous inflammation were observed in numerous tissues, primarily at the high dose. One granulomatous lesion was observed in the liver at 6000 ppm and five were observed in the bladder at 9500 ppm. The presence of spindle-shaped clear spaces in tissues and foreign body type giant cells suggested a reaction to crystal formation (JMPR (1992)). In 4-week oral administration (mixed diet) tests using mice, crystalline deposits and effects on the liver were observed at 6000 ppm or higher, and granulomatous lesions surrounding crystal deposits were found frequently in the urinary bladder and occasionally in liver parenchyma, myocardium, diaphragmatic muscle, and skeletal muscle. It was speculated that the crystals contained a major metabolite of iprodione (32490 R.P.), which was identified in the liver. Liver effects included increased weight, pale and mottled appearance on gross examination, and swelling of hepatocytes to form large homogeneous areas in the centrilobular region of the liver. Histopathological changes in the testes and spleen were observed at doses levels above 6000 ppm (JMPR (1992)). In 3-month oral administration (mixed diet) tests using rats, effects on the liver, spleen and thymus were observed at high doses in small examinations carried out (JMPR (1992)); however these observations were made on animals that received doses higher than guidance values.
10 Aspiration hazard Classification not possible - - - - No data available.

ENVIRONMENTAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
11 Hazardous to the aquatic environment (Acute) Category 1 Warning H400: Very toxic to aquatic life P273: Avoid release to the environment.
P391: Collect spillage.
P501: Dispose of contents/container to ...
Since its 48h-EC50 = 0.25 mg/L for crustaceans (Daphnia magna) (IUCLID 2000), the substance was classified into Category 1.
11 Hazardous to the aquatic environment (Long-term) Category 1 Warning H410: Very toxic to aquatic life with long lasting effects P273: Avoid release to the environment.
P391: Collect spillage.
P501: Dispose of contents/container to ...
Since its classification for acute toxicity is Category 1, and it is not rapidly degradable (28-day degradability following OECD TG 301B = 0.16-0.2% (IUCLID 2000)), the substance was classified into Category 1.


NOTE:
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.

Reference:
Reference Manual

Definitions / Abbreviations

Model Label by MHLW

MHLW Website (in Japanese Only)

Model SDS by MHLW

MHLW Website (in Japanese Only)


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