NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	102851-06-9
Chemical Name	Alpha-cyano-3-phenoxybenzyl N-(2-chloro-alpha,alpha,alpha-trifluoro-p-tolyl)-D-valinate; Fluvalinate
Substance ID	R01-B-072
Classification year (FY)	FY2019
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

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2013 revised edition (Ver. 1.1))
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

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	Category 4	- Warning	H227	P370+P378 P210 P280 P403 P501	It was classified in Category 4 based on a flash point of 90 deg C (closed cup) (ATSDR (2003)).
7	Flammable solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	No data available.
10	Pyrophoric solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to liquid substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	The substance is an organic compound containing fluorine, chlorine, and oxygen, which are chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	No data available.
17	Desensitized explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 3. Besides, although the test in (2) is a non-GLP test, it is considered that the LD50 value in (2) was lower than that of (1) due to the absorption ability of this substance caused by the difference in the solvents. [Evidence Data] (1) LD50 (1% Tween 80) for rats: male: 1,698 mg/kg, female: 1,396 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)) (2) LD50 (corn oil) for rats: male: 282 mg/kg, female: 261 mg/kg (EPA Pesticide (2005), Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." [Evidence Data] (1) LD50 for rabbits: >2,000 mg/kg (EPA Pesticide (2005)) (2) LD50 for rats: >2,000 mg/kg (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Category 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1), it was classified in Category 2. [Evidence Data] (1) LC50 for rats (mist, 4 hours): male: ca. 465 mg/m3 (0.465 mg/L), female: 439 mg/m3 (0.439 mg/L) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1)-(3), it was classified as "Not classified." [Evidence Data] (1) In a skin irritation test according to EPA OPPTS 870.2500 with rabbits, its primary irritation index (PII) was 0.8 (EPA Pesticide (2005)). (2) In a skin irritation test in which this substance (0.5 mL) was semi-occlusively applied to rabbits for 4 hours, mean scores at 24/48/72 hours were 0.44 and 0.11 for erythema and edema, respectively (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (3) In a skin irritation test with rabbits, no irritation was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). [Reference Data, etc.] (4) It was classified in "Skin Irrit. 2 (H315)" in the EU CLP classification (EU CLP classification (Access on August 2019)).
3	Serious eye damage/eye irritation	*	- -	-	-	[Rationale for the Classification] There are data in (1), however, since the details cannot be confirmed, it was classified as "Classification not possible." [Reference Data, etc.] (1) In an eye irritation test according to EPA OPPTS 870.2400 with rabbits, discharge up to 1-hour post instillation, and conjunctival redness and swelling for up to 3 days were observed (EPA Pesticide (2005)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1B	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1B. Since new data were obtained, the classification was changed. [Evidence Data] (1) In a skin sensitization test (maximization method, GLP-compliant, intradermal induction: 5%, induction (topical application): 50%, challenge: 15%) with guinea pigs, conducted according to the Guideline of the Ministry of Agriculture, Forestry and Fisheries, a positive rate was determined as 39% (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)). (2) In a skin sensitization test (maximization method) with guinea pigs, moderate skin sensitization was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). [Reference Data, etc.] (3) In a skin sensitization test according to EPA OPPTS 870.2600 with guinea pigs, no sensitization was observed (EPA Pesticide (2005)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), since all the in vivo and in vitro tests were negative, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, there is a report of a negative result in a chromosomal aberration test with rats (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016), Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (2) As for in vitro, there are reports of negative results in a bacterial reverse mutation test, and a chromosomal aberration test, an unscheduled DNA synthesis test and a gene mutation test with cultured mammalian cells (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016), Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Based on the classification results by other organizations in (1), it was classified as "Not classified" in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified as "NL (Not Likely to be Carcinogenic to Humans)" by EPA (EPA Pesticide (2005)). [Reference Data, etc.] (2) In a combined chronic toxicity/carcinogenicity study in which this substance was administered to rats for 2 years by gavage, a significantly increased incidence of fibroadenoma of the mammary gland in females was observed. However, it was within the range of the historical control data (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (3) In a carcinogenicity study in which this substance was administered to mice for 2 years by feeding, no increased incidence of tumors was found (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)).
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Based on (1), since transient tremors were observed in F1 and F2 pups, and in the lactation period for F1 pups, effects via lactation cannot be denied. However, there is no clear evidence. Based on (2) and (3), at doses at which maternal toxicity was observed, no clear developmental effects were observed. Therefore, it was classified as "Not classified." Besides, the classification was changed by using a new information source. [Evidence Data] (1) In a two-generation reproductive toxicity study with rats by feeding, lower body weight and transient tremors were observed in F1 and F2 pups (during lactation period for F1 pups) at the dose at which skin ulcers and decreased body weight gain were observed as parental animal toxicity, whereas no effects on fertility were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (2) In a developmental toxicity test in which female rats were dosed by gavage on gestational days 6-15, skeletal variations were observed in fetuses at the dose at which maternal toxicity (salivation) was observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (3) In a developmental toxicity test in which female rabbits were dosed by gavage on gestational days 6-18, no abnormality was observed in fetuses at the dose at which maternal toxicity (decreased body weight, etc.) was observed. Besides, though skeletal and visceral abnormalities were reported, since there is no difference in the incidences from the control group, the effects were denied (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system, respiratory organs)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] There is no report regarding single exposure to this substance in humans. As for experimental animals, effects on the nervous system through the oral route as in (1) and (2), and effects on the nervous system and respiratory organs through the inhalation route as in (3) were observed. Since concentrations at which the effects were observed in (3) corresponds to Category 1, it was classified in Category 1 (nervous system, respiratory organs). The classification result was changed from the previous classification by using a new information source. [Evidence Data] (1) In a single oral exposure test with rats, salivation, sweating, sedation, gait disturbance and dyspnea were observed at or above 1,000 mg/kg (males) or 592 mg/kg (females). Death was observed at or above 1,300 mg/kg (males) or 769 mg/kg (females). The lowest dose at which effects were observed corresponds to Category 2 (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (2) In a single oral exposure test with mice, gait disturbance, hyperactivity, salivation and abnormal gait were observed at or above 1,200 mg/kg (females and males). Clonic seizure was observed at or above 1,200 mg/kg (males) or 1,440 mg/kg (females) as well. Death was observed at or above 2,074 mg/kg (males) or 1,440 mg/kg (females). The lowest dose at which effects were observed corresponds to Category 2 (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (3) In a test in which rats (females and males, 5 animals/group) were exposed to the mist of this substance at 0.097-0.778 mg/L (corresponding to Category 1) once for 4 hours by inhalation, muscle relaxation, abnormal gait, salivation, nasal discharge, urinary incontinence, gasping, abdominal distention, hypersensitivity, pale extremities and snores were observed. However, they disappeared 3 days post exposure. There is no description of the lowest dose at which effects were observed. However, it is considered to be around LC50 (ca. 0.465 mg/L (males) or 0.439 mg/L (females)) or below. Necropsy revealed ecchymoses and congestion in the lungs of all the dead animals, and pulmonary emphysema in one each male animal in the 0.521 mg/L group and 0.778 mg/L group among the surviving animals (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017), A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
9	Specific target organ toxicity - Repeated exposure	Category 2 (blood system)	Warning	H373	P260 P314 P501	[Rationale for the Classification] Based on (1)-(4), it was classified in Category 2 (blood system). Besides, other than this, effects on the skin and eyes were observed. However, the cause of skin lesions was considered to be the animals' damaging their skin themselves due to the pruritus-inducing property of this substance, and effects to the eyes were judged to be effects related to this, and so these were not adopted as target organs. By examining using new information sources, the classification result was changed from the previous classification. [Evidence Data] (1) In a 90-day repeated dose toxicity test with rats by feeding, skin lesions such as loss of fur or crusting, etc. were observed in males at 150 ppm (males/females: 8.51/8.94 mg/kg/day, within the range of Category 1). Also, reduced erythrocyte counts, etc. in females and males, and reduced hematocrit and hemoglobin, and skin lesions such as loss of fur or crusting, etc. in females were observed at 450 ppm (males/females: 25.8/26.5 mg/kg/day, within the range of Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (2) In a 90-day repeated dose toxicity test with rats by feeding, reduced hemoglobin and hematocrit, etc., skin lesions and associated lymphadenitis in females and males, and reduced erythrocyte counts, etc. in females were observed at or above 30 mg/kg/day (within the range of Category 2). Also, hypersalivation and abnormal gait in females and males, a reduced number of erythrocytes, etc. in males, and an increased number of leukocytes, increased serum AST and reduced ovary weight, etc. in females were observed at 50 mg/kg/day (within the range of Category 2) (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (3) In a 90-day repeated dose toxicity test with mice by feeding, skin lesions in males at or above 3 mg/kg/day (within the range of Category 1) and in females at or above 30 mg/kg/day (within the range of Category 2), and reduced hemoglobin in females at or above 50 mg/kg/day (within the range of Category 2) were seen, and at 100 mg/kg/day (within the range of Category 2), skin lesions, etc. in females and males, and reduced hematocrit and erythrocyte counts, an increased number of leukocytes, reduced ovary weight, hypoplasia of the ovary and increased parovarian cysts, etc. in females, were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). (4) In a 1-year repeated dose toxicity test with dogs by gavage, vomiting, skin lesions and dermatitis were seen in males at or above 5 mg/kg/day (within the range of Category 2), and at 25 mg/kg/day (within the range of Category 2), diarrhea and reductions in hemoglobin, hematocrit and the number of erythrocytes in females and males, and vomiting, skin lesions and dermatitis, etc. in females, were observed (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)). [Reference Data, etc.] (5) The effects of dosing this substance are observed mainly in general clinical observation (salivation, hypolocomotion, abnormal gait, etc.), body weight (reduced body weight gain), blood (anemia) and skin (loss of fur, crust, etc.). It is considered that animals' damaging their skin themselves due to the pruritus-inducing property of fluvalinate is the cause of skin lesions (Risk Assessment Report (Pesticides and Veterinary Medicinal Products) (Food Safety Commission of Japan, 2017)).
10	Aspiration hazard	*	- -	-	-	[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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.00195 mg/L for fish (Cyprinus carpio) (A pesticide abstract and evaluation report (Food and Agricultural Materials Inspection Center, 2016)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because it is not rapidly degradable (BIOWIN), and it was classified in Category 1 in acute toxicity.
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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