Chemical Name：tolylfluanid (ISO); dichloro-N-[(dimethylamino)sulphonyl]fluoro-N-(p-tolyl)methanesulphenamide
CAS：731-27-1

Hazard class		Classification	Symbol	Signal word	Hazard statement	Precautionary statement	Rationale for the classification
1	Acute toxicity （Oral）	Not classified	-	-	-	-	Since its rat LD50 value is > 5000 mg/kg bw (JMPR (2002)), the substance was classified into "Not classified".
1	Acute toxicity （Dermal）	Not classified	-	-	-	-	Since its rat LD50 value is > 5000 mg/kg bw (JMPR (2002)), the substance was classified into "Not classified".
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）	Category 2		Danger	H330: Fatal if inhaled	P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P403+P233: Store in a well-ventilated place. Keep container tightly closed. P260: Do not breathe dust/fume/gas/mist/vapours/spray. P271: Use only outdoors or in a well-ventilated area. P284: Wear respiratory protection. P310: Immediately call a POISON CENTER or doctor/physician. P320: Specific treatment is urgent （see ... on this label）. P405: Store locked up. P501: Dispose of contents/container to ...	Based on its rat LC50 values of 0.16, 0.20, and 0.38 mg/L/4h (JMPR (2002)), the substance was classified into Category 2. Since the test concentration was 0.16 mg/L, which was higher than the saturated vapour concentration of the test substance (0.028 mg/L), the test is thought to have been conducted with the substance in a dust state.
2	Skin corrosion/irritation	Category 2		Warning	H315: Causes skin irritation	P302+P352: IF ON SKIN: Wash with plenty of soap and water. P332+P313: If skin irritation occurs: Get medical advice/attention. P264: Wash ... thoroughly after handling. P280: Wear protective gloves/protective clothing/eye protection/face protection. P321: Specific treatment （see ... on this label）. P362: Take off contaminated clothing and wash before reuse.	Two tests have been conducted using rabbits; one test concluded that the substance was severely irritating (JMPR (2002)) and the other test found that it caused no irritation (using 1% water solution) (JMPR (2002)). Considering that the EU rated the substance as Xi; R36/37/38, it was classified into Category 2.
3	Serious eye damage/eye irritation	Category 2A		Warning	H319: Causes serious 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. P280: Wear protective gloves/protective clothing/eye protection/face protection.	In tests using rabbits, the substance was found to be severely or moderately irritating (JMPR (2002)). Furthermore, the EU rated the substance as Xi; R36/37/38. Thus, it was classified into Category 2A.
4	Respiratory sensitization	Classification not possible	-	-	-	-	No data available.
4	Skin sensitization	Category 1		Warning	H317: May cause an allergic skin reaction	P302+P352: IF ON SKIN: Wash with plenty of soap and water. P333+P313: If skin irritation or rash occurs: Get medical advice/attention. P261: Avoid breathing dust/fume/gas/mist/vapours/spray. P272: Contaminated work clothing should not be allowed out of the workplace. P280: Wear protective gloves/protective clothing/eye protection/face protection. P321: Specific treatment （see ... on this label）. P363: Wash contaminated clothing before reuse. P501: Dispose of contents/container to ...	A Buehler test using guinea pigs concluded that the substance was not sensitizing (JMPR (2002)). On the other hand, a maximization test using guinea pigs revealed that it was sensitizing (JMPR (2002)), and two tests using mice (local lymph node assays) concluded that it was possibly a sensitizing substance and that it was sensitizing (JMPR (2002)). In addition, the EU rated the substance as Xi; R43. Based on this information, the substance was classified into Category 1.
5	Germ cell mutagenicity	Not classified	-	-	-	-	All of the following tests yielded negative results: dominant lethal tests using mice (in vivo heritable mutagenicity tests using germ cells), germ-cell cytogenetic assays using Chinese hamsters (in vivo mutagenicity tests using germ cells), spot tests using mice, micronucleus tests using bone marrow cells of mice or hamsters, and chromosomal aberration tests using bone marrow cells of hamsters (the latter two tests were in vivo mutagenicity tests using somatic cells) (JMPR (2002)). Based on these negative results, the substance was classified into "Not classified". Also, in vitro mutagenicity tests (Ames tests and gene mutation tests using V79 or CHO cells) yielded negative results, chromosomal aberration tests using V79 cells yielded weakly positive results, mouse lymphoma assays yielded positive results, and cytogenetic assays using human lymphocytes yielded positive results (JMPR (2002)).
6	Carcinogenicity	Not classified	-	-	-	-	Two-year oral route exposure tests, in which rats or mice were fed with a diet containing the substance, were conducted twice for each animal species. In these tests, dose-dependent mortality rates were not detected although reduced body-weight gain was observed (JMPR (2002)). In one of the rat tests, only malignant uterine tumours appeared at higher incidence in all treated groups as compared with controls. Because these tumors develop under normal circumstances, it is reported that the difference observed was likely to be attributed to low incidences of tumor development in control groups (JMPR (2002)). In the other rat test, thyroid follicular-cell adenomas were observed in animals treated with the highest dose (7500 ppm). The probable cause of adenoma was related to the increased concentrations of the thyroid stimulating hormone and alterations in the thyroid feedback mechanism, so the concentration levels that do not affect the thyroid gland would not induce carcinogenicity in humans (JMPR (2002)). With regard to mice, hepatocellular adenomas and pulmonary adenomas were observed in both treated and control groups, and incidences of tumor development due to exposure to the substance did not increase in either mouse tests (JMPR (2002)). Thus, since the rat and mouse tests conducted twice did not show evidence of carcinogenicity, the substance was classified into "Not classified".
7	Reproductive toxicity	Not classified	-	-	-	-	In three two-generation reproduction tests using rats, no effects on reproductive functions or fertility were detected (JMPR (2002)). In addition, in rats and rabbits that underwent oral route exposure during the organogenetic period, no effects on the development of offspring were observed (JMPR (2002)). Based on these negative results, the substance was classified into "Not classified".
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory system)		Danger	H370: Causes damage to organs (respiratory system)	P307+P311: IF exposed: 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. P321: Specific treatment （see ... on this label）. P405: Store locked up. P501: Dispose of contents/container to ...	Its rat LC50 via single inhalation exposure (dust) is 0.16-0.20 mg/kg. The symptoms of exposure include not only morphological changes in the respiratory tracts observed in dead rats, but also extreme difficulties in breathing, respiratory sounds and sneezing, serous nasal discharge, and cyanosis after exposure (JMPR (2002)). Based on these results, the substance was classified into Category 1 (respiratory system). On the other hand, a test was conducted in which rats underwent single oral administration with doses up to 2000 mg/kg, with neurotoxicological studies being its main purpose. In this test, other than symptoms of reversible general toxicity being detected, no specific neurotoxicity appeared and the effect of exposure was not observed from the histopathological standpoint (JMPR (2002)). In addition, single oral administration tests, in which rats or rabbits were applied with 500 mg/kg, concluded that severe toxic effects were not detected in both animal species (JMPR (2002)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory system)		Danger	H372: Cause damage to organs through prolonged or repeated exposure (respiratory system)	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. P314: Get medical advice/attention if you feel unwell. P501: Dispose of contents/container to ...	Rats that underwent inhalation exposure for four weeks exhibited labored breathing and abnormal respiratory sounds, as well as resulting in death cases at 0.05 mg/L/6hr (90-day conversion value: 0.015 mg/L/6hr). In addition, in terms of histopathology, the following were observed: squamous metaplasia and hyperkeratosis of the anterior nasal cavities, squamous metaplasia of the larynx, epithelial desquamation and round-cell infiltration of the trachea, and fibrosis around the bronchia and in lungs. In some cases, these symptoms were detected at the doses of 0.01-0.004 mg/L (90-day conversion values: 0.003-0.001 mg/L) (JMPR (2002)). All of these effects on the respiratory system developed with the doses equivalent to the Category 1 guidance values, so the substance was classified into Category 1 (respiratory system). On the other hand, serious toxic effects were not recognized with doses that fall under the range of guidance values in the following tests: four oral route exposure tests in which rats were administered with a diet containing the substance for 3 months, 13 weeks, 2 years, or 105 weeks; one test in which dogs were fed with a diet containing the substance for 92 days; two tests in which dogs were orally administered with a capsule containing the substance for 52 weeks; and a test in which mice were administered with a diet containing the substance for 105 weeks (JMPR (2002)). Furthermore, in 3-month, 13-week, and 2-year rat tests, serious toxic effects were not detected with administration doses that were higher than the upper limit of the guidance values (JMPR (2002)). As additional information, in tests in which mice were administered with doses that were higher than the range of guidance values for 105 weeks, the following were observed: the basophilic intranuclear inclusion bodies and lymphohistiocytosis in the liver, and vacuolization of the tubular epithelium in the kidney (JMPR (2002)). In addition, in rabbits that underwent dermal exposure for 3 weeks, no systemic toxicity was reported (except on the skin where application was made) even in the highest dose groups exposed to 300 mg/kg/day (90-day correction value: approximately 70 mg/kg/day) (JMPR (2002)); however, these results alone are insufficient for classification purposes.
10	Aspiration hazard	Classification not possible	-	-	-	-	No data available.