GHS Classification Results by the Japanese Government

日本語で表示



GENERAL INFORMATION
Item Information
CAS RN 548-62-9
Chemical Name [4-{Bis(4-dimethylaminophenyl)methylene}-2,5-cyclohexadien-1-ylidene]dimethylammonium chloride; C.I. Basic Violet 3; Crystal Violet
Substance ID R01-B-004
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 FY2007  
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 *
-
-
- - Solid (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 *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5 Gases under pressure *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6 Flammable liquids *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7 Flammable solids *
-
-
- - No data available.
8 Self-reactive substances and mixtures *
-
-
- - There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9 Pyrophoric liquids *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10 Pyrophoric solids *
-
-
- - No data available.
11 Self-heating substances and mixtures *
-
-
- - No data 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 *
-
-
- - Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14 Oxidizing solids *
-
-
- - The substance is an organic compound containing chlorine (but not fluorine or oxygen), which is a chloride ion and does not contribute to oxidization. Therefore, it was classified as "Not classified."
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 *
-
-
- - Classification is not possible because test methods applicable to solid substances are not 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]
Since (1) corresponds to Category 3 and (2) corresponds to Category 4 of the GHS classification guidance for the Japanese government, it was classified in Category 3 on the safety side. The category was changed by reviewing the information sources.

[Evidence Data]
(1) LD50 for rats: 180 mg/kg (JECFA FAS69 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018))
(2) LD50 for rats: 420 mg/kg (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018))
1 Acute toxicity (Dermal) *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Gases) *
-
-
- - [Rationale for the Classification]
Solid (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) *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
2 Skin corrosion/irritation *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.

[Reference Data, etc.]
(1) Although not used as a basis for classification due to lack of detailed description, it has been reported in humans that exposures to this substance were associated with dermal irritation and sensitization, ocular irritation, and mucosal irritation (JECFA TRS 988 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
3 Serious eye damage/eye irritation Category 2


Warning
H319 P305+P351+P338
P337+P313
P264
P280
[Rationale for the Classification]
Based on (1), it was classified in Category 2. Besides, the category was changed because human cases were confirmed.

[Evidence Data]
(1) Eye irritation, pain, diminution of vision, moderate lid edema and blepharospasm, conjunctival congestion, and corneal opacity and edema were observed in a case (60-year-old man) who had a 1% solution of this substance accidentally instilled into his eyes (HSDB (Access on May 2019), Dhir et al., Indian J. Ophthalmol. 30 21-22 (1982)).

[Reference Data, etc.]
(2) There were case reports in humans that exposures to this substance were associated with dermal irritation and sensitization, ocular irritation, and mucosal irritation (JECFA TRS 988 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
4 Respiratory sensitization *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization *
-
-
- - [Rationale for the Classification]
There is a description of (1), but it was classified as "Classification not possible" due to lack of data.

[Reference Data, etc.]
(1) There were case reports in humans that exposures to this substance were associated with dermal irritation and sensitization, ocular irritation, and mucosal irritation (JECFA TRS 988 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
5 Germ cell mutagenicity *
-
-
- - [Rationale for the Classification]
Based on (1) and (2), it was classified as "Not classified.

[Evidence Data]
(1) As for in vivo, it was negative in a DNA damage test and a chromosomal aberration test with mice (JECFA FAS69 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(2) As for in vitro, there were positive, negative or equivocal results for bacterial revertant mutation tests, positive or negative results for chromosome aberration tests with cultured mammalian cells, and a positive result for a chromosome aberration test with human lymphocytes (JECFA FAS69 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018), NTP DB (Access on May 2019)).
6 Carcinogenicity Category 1B


Danger
H350 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
There are no available reports on carcinogenicity in humans.
Based on (1) and (2), since increased incidences of tumors at multiple sites, including malignant tumors, were observed in 2 species of experimental animals, it was classified in Category 1B. Besides, the category was changed from the previous classification by reconfirming the data.

[Evidence Data]
(1) In a carcinogenicity study in which mice were given this substance (100, 300, and 600 mg/kg feed) by feed for two years, significantly increased malignant tumors of the liver at 600 mg/kg in males, malignant tumors of the liver at or above 300 mg/kg in females, and significantly increased adenoma of the Harderian gland at or above 100 mg/kg in females were observed. In addition, a significant increase in type A reticulum cell sarcomas (synonymous with histiocytic sarcoma) in the uterus (at or above 300 mg/kg in females), bladder, vagina, and ovaries (600 mg/kg in females) were observed (JECFA FAS69 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(2) In a carcinogenicity study in which rats were given this substance (100, 300, and 600 mg/kg feed) by feed for two years, significantly increased follicular cell adenocarcinomas of the thyroid gland at 600 mg/kg in males and at or above 300 mg/kg in females, and significantly increased hepatocellular adenomas at or above 300 mg/kg in males and females, were observed (JECFA FAS69 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).

[Reference Data, etc.]
(3) As for classification results by domestic and international organizations, this substance alone was classified in Carc.2 in the EU CLP (EU CLP classification (Access on May 2019)).
7 Reproductive toxicity *
-
-
- - [Rationale for the Classification]
No reproductive effects or teratogenicity were observed even at doses where parental toxicity was observed in the 3-generation reproductive toxicity study in (1). In addition, as shown in (2) and (3), also in developmental toxicity tests with two animal species, at doses where severe maternal toxicity were observed, variations in fetuses or lower fetal weights were observed but no malformations were observed. Therefore, it was classified as "Not classified."
Besides, the category was changed from the previous classification by reviewing the evidence data of the classification.

[Evidence Data]
(1) In a 3-generation reproductive toxicity test with rats, lower body weights were observed in parental animals of all generations. No reproductive effects were observed, but in pups, focal dilatation of the renal cortex and tubules, necrosis of the thymus, and red pulp hematopoietic cell proliferation of the spleen inversely correlated with dose were observed in all treatment groups in the F3a generation. Besides, no malformation was observed in a teratogenicity test conducted in the F3b generation (JECFA FAS69 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(2) In a developmental toxicity test with rats administered by gavage, hydroureter and hydronephrosis which were considered to be visceral variations, and short ribs which were considered to be skeletal variations were observed at doses where maternal toxicity (reduced body weight gain, and increased clinical signs of toxicity (wheezing, lethargy, weakness, diarrhea, lacrimation, rough coat)) was observed, but no malformations were observed (JECFA FAS69 (2014), NTP DB (Access on May 2019), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(3) In a developmental toxicity test with rabbits administered by gavage, lower fetal weight was observed at doses where maternal toxicity (increased mortality, reduced body weight gain, wheezing, diarrhea, congestion, dyspnea, cyanosis, etc.) was observed, but no malformations were observed (JECFA FAS69 (2014), NTP DB (Access on May 2019), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
8 Specific target organ toxicity - Single exposure *
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data. Based on (1) and (2), symptoms indicating effects on the gastrointestinal tract and central nervous system were observed in humans and experimental animals, these are considered to be due to the irritancy of this substance and its secondary effects. Since there is no other information to enable identifying the target organ, it was classified as "Classification not possible."

[Reference Data, etc.]
(1) Although the number of administrations was unknown, about 1/3 of patients who were administered this substance as a drug (anthelmintic) complained of gastrointestinal tract irritation, nausea, vomiting, diarrhea and slight abdominal pain, but when administration was discontinued, these symptoms disappeared (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(2) In acute oral administration tests with rats, mice, rabbits, guinea pigs, dogs and cats, lethargy, ataxia, diarrhea, thirst, emesis, and weight loss were observed, and histologically, findings which were evidence of inflammation, congestion, and hemorrhage of the gastrointestinal tract were observed (JECFA FAS69 (2014)). It is described in the original source article that lethargy was probably due to body fluid and electrolyte loss associated with stimulation of the gastrointestinal tract (Hodge et al., Toxicol Appl Pharmacol. 22: 1-5 (1972)).
9 Specific target organ toxicity - Repeated exposure Category 2 (liver, reproductive organs (female))


Warning
H373 P260
P314
P501
[Rationale for the Classification]
In the oral dose toxicity tests with mice and rats in (1) and (2), changes in the liver, spleen, and ovary were observed within the range of Category 2. Among these, the changes in the spleen were not judged to be hazardous effects. Therefore, it was classified in Category 2 (liver, reproductive organs (women)). Besides, the information in RTECS that was adopted as the evidence for classification in the previous classification was not used because it is the information source in List 3, information in the new sources was added, and the classification result was changed from the previous classification.

[Evidence Data]
(1) In a chronic toxicity and carcinogenicity test with mice, when mice were administered by feed at 100-600 mg/kg (male: 10.7-64.3 mg/kg/day, female: 14.3-71.4 mg/kg/day) for 24 months, as non-neoplastic lesions, high mortality rates, increases in erythropoiesis in the spleen, and atrophy of the ovaries in females at or above 100 ppm (10.7 mg/kg/day, within the range of Category 2), high values of ALT and AST in females at or above 300 ppm (32.1 mg/kg/day, within the range of Category 2), and high mortality rates and high values of ALT and AST in males at 600 ppm (64 mg/kg/day, within the range of Category 2) were observed (JECFA FAS69 (2014), JECFA TRS 988 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(2) In a chronic toxicity and carcinogenicity test with rats, when administered by feed at 100-600 mg/kg (male: 30-160 mg/kg/day, female: 40-200 mg/kg/day) for 24 months, as non-neoplastic lesions, mixed and regenerative foci in the liver in males and females at or above 100 ppm (male: 30 mg/kg/day, female: 40 mg/kg/day, both within the range of Category 2), in males and females, eosinophilic foci in the liver in males and females, liver centrilobular necrosis in males, and increased mortality rate in females at or above 300 ppm (male: 80 mg/kg/day, female: 100 mg/kg/day, both within the range of Category 2), and clear cell foci in the liver, follicular cysts in the thyroid gland, red pulp hyperplasia, and mesenteric lymph node hyperplasia in males, and liver centrilobular necrosis in females were observed at 600 ppm (male: 160 mg/kg/day, female: 200 mg/kg/day, both exceeding Category 2) (JECFA FAS69 (2014), JECFA TRS 988 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).

[Reference Data, etc.]
(3) An epidemic of nosebleeds in apple packers who used packing trays dyed with this substance was reported (JECFA FAS69 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(4) In a test in which rats were dosed by feed at up to 500 mg/kg feed for 90 days, a slight body weight loss was observed, but no clear effects associated with the administration were observed (JECFA FAS69 (2014), JECFA TRS 988 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
(5) In a test in which dogs were dosed by feed at up to 516 mg/kg feed for 90 days, an increased liver weight was observed, but no clear effects associated with the administration were observed (JECFA FAS69 (2014), JECFA TRS 988 (2014), Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2018)).
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) Classification not possible
-
-
- - Classification not possible due to lack of data.
11 Hazardous to the aquatic environment Long term (Chronic) Classification not possible
-
-
- - Classification not possible due to lack of data.
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.

To GHS Information