GHS Classification Results by the Japanese Government

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GENERAL INFORMATION
Item Information
CAS RN 56-75-7
Chemical Name 2,2-Dichloro-N-[2-hydroxy-1-(hydroxymethyl)-2-(4-nitrophenyl)ethyl]acetamide; Chloramphenicol
Substance ID R02-B-069-MHLW, MOE
Classification year (FY) FY2020
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 (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

PHYSICAL HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Explosives Classification not possible
-
-
- - There is a chemical group associated with explosive properties (nitro group) present in the molecule, and the calculated oxygen balance is -114, higher than the criteria: -200, but the classification is not possible due to no data.
2 Flammable gases Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
3 Aerosols Not classified (Not applicable)
-
-
- - Not aerosol products. It was classified as "Not classified."
4 Oxidizing gases Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
5 Gases under pressure Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
6 Flammable liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
7 Flammable solids Classification not possible
-
-
- - No data available. Besides, there is information that it is combustible (GESTIS (Access on May 2020)).
8 Self-reactive substances and mixtures Classification not possible
-
-
- - There is a chemical group associated with explosive properties (nitro group) present in the molecule, but the classification is not possible due to no data.
9 Pyrophoric liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
10 Pyrophoric solids Classification not possible
-
-
- - No data available.
11 Self-heating substances and mixtures Classification not possible
-
-
- - No data available.
12 Substances and mixtures which, in contact with water, emit flammable gases Not classified (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). It was classified as "Not classified."
13 Oxidizing liquids Not classified (Not applicable)
-
-
- - Solid (GHS definition). It was classified as "Not classified."
14 Oxidizing solids Classification not possible
-
-
- - The substance is an organic compound containing oxygen (but not fluorine or chlorine), which is chemically bonded to the element other than carbon or hydrogen (N). However, the classification is not possible due to no data.
15 Organic peroxides Not classified (Not applicable)
-
-
- - Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified."
16 Corrosive to metals Classification not possible
-
-
- - Classification is not possible because test methods applicable to solid substances are not available.
17 Desensitized explosives Classification not possible
-
-
- - There is a chemical group associated with explosive properties (nitro group) present in the molecule, but the classification is not possible due to no data.

HEALTH HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Acute toxicity (Oral) Not classified
-
-
- - [Rationale for the Classification]
It was classified as "Not classified" from (1).

[Evidence Data]
(1) LD50 for rats: 2,500 mg/kg (GESTIS (Access on May 2020))
1 Acute toxicity (Dermal) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Gases) Not classified
-
-
- - [Rationale for the Classification]
Solid (GHS definition). It was classified as "Not classified."
1 Acute toxicity (Inhalation: Vapours) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
2 Skin corrosion/irritation Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
3 Serious eye damage/eye irritation Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Respiratory sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - [Rationale for the Classification]
Classification not possible due to lack of data.
5 Germ cell mutagenicity Category 2


Warning
H341 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
It was classified in Category 2 from (1) - (3). By the review of information sources, the classification result was changed.

[Evidence Data]
(1) As for in vivo, it was reported to be negative in a dominant lethal test with mice (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)), positive in a chromosomal aberration test with mice (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014), EU EMEA (1996), JECFA TRS 925 (2004)), and negative in micronucleus tests with rats and mice (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014), EU EMEA (1996), JECFA TRS 925 (2004)).
(2) As for in vitro, it was reported to be negative and positive in bacterial reverse mutation tests (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014), MAK (DFG) vol.9 (1998)), negative and positive in DNA repair tests using E. Coli (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)), positive in a DNA fragmentation detection test with cultured mammalian cells (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014), EU EMEA (1996)), negative and positive in sister chromatid exchange tests, and positive in a chromosomal aberration test with human lymphocytes (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014), EU EMEA (1996), JECFA TRS 925 (2004)).
(3) Chloramphenicol was reported to be genotoxic to in vivo somatic cells (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
6 Carcinogenicity Category 1B


Danger
H350 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
It was classified in Category 1B based on (1) - (3).

[Evidence Data]
(1) As for classification results by domestic and international organizations, it was classified in Group 2A by IARC (IARC 50 (1990)) and R by NTP (NTP Roc (14th, 2016)).
(2) Although it was reported only as a summary, in a carcinogenicity test by drinking water administration of this substance to mice, increased incidences of lymphoma in two strains of mice and an increased incidence of hepatocellular carcinoma in one strain of mice were observed (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014), EU EMEA (1996)).
(3) This substance induced aplastic anemia, which was related to the occurrence of leukemia (IARC 50 (1990)).
7 Reproductive toxicity Category 1B


Danger
H360 P308+P313
P201
P202
P280
P405
P501
[Rationale for the Classification]
Based on (1) to (5), in developmental toxicity studies, an increase in embryo or fetal death rate was observed. Although the presence or absence of maternal toxicity was unknown, it was described in (4) that only lower body weight was observed at the highest dose. Therefore, it was judged that an increase in embryo or fetal death rate was observed at a dose at which no clear maternal toxicity was observed. As a result, it was classified in Category 1B. A new information source was used and the classification results were changed from the previous classification.

[Evidence Data]
(1) In a developmental toxicity study with pregnant mice dosed by gavage, an increase in embryo or fetal death rate was observed. The embryo or fetal death rate was 71% and 100% at 1,000 mg/kg/day and 2,000 mg/kg/day, respectively. At 500 mg/kg/day, the embryo or fetal death rate was 31% while it was 24% in the control group (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(2) In a developmental toxicity study with pregnant rats dosed by gavage, an increase in embryo or fetal death rate was observed. The embryo or fetal death rate was 63% (historical control: 23%) when 500 mg/kg/day was given on days 5 to 15 of gestation. In addition, umbilical hernia was observed in 36% of rats dosed by oral administration of 2,000 mg/kg/day on days 6 to 8 of gestation while it was observed in 11% of rats dosed by single administration on day 8 of gestation (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(3) In a developmental toxicity study with pregnant rabbits dosed by gavage, an increase in embryo or fetal death rate was observed. At 500 mg/kg/day, no increase in the number of fetal deaths was observed, while at 1,000 and 2,000 mg/kg/day, the fetal mortality was 25 and 58%, respectively (historical control: 10%). A delay in ossification was pronounced in the dosed groups but the incidence of malformations was low (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(4) In developmental toxicity studies with rats and mice dosed by oral administration of 500 to 2,000 mg/kg/day and with rabbits dosed by oral administration of 500 and 1,000 mg/kg/day, increases in the incidence of embryonic and fetal deaths and fetal growth retardation were observed in all three species. Teratogenic effects and predominantly umbilical hernia were observed only in rats. Pregnant animals showed no toxic sign except lower body weight at the highest dose (IARC 50 (1990), HSDB (Access on May 2020)). The data was the same as in (1) to (3).
(5) In teratogenicity studies with rats and rabbits, this substance showed no teratogenic effects but caused a high incidence of fetal deaths even at the lowest dose level tested (EU EMEA (1996)).

[Reference Data, etc.]
(6) The Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014) stated that "although it was judged that there were insufficient data available to assess reproductive and developmental toxicity, the substance was presumed to have reproductive and developmental toxicity, and therefore, there was concern about its effects on humans."
(7) It was reported that, in rats dosed on days 9 to 11 of gestation, malformations, including hydrocephalus and cleft palate, were observed in fetuses (IARC 10 (1976), HSDB (Access on May 2020)). This data was not cited in the IARC 50 (1990).
8 Specific target organ toxicity - Single exposure Classification not possible
-
-
- - [Rationale for the Classification]
Classification was not possible due to lack of data.
9 Specific target organ toxicity - Repeated exposure Category 1 (hematopoietic system, nervous system, circulatory system, digestive organ)


Danger
H372 P260
P264
P270
P314
P501
[Rationale for the Classification]
Based on (1) to (7), it was classified in Category 1 (hematopoietic system, nervous system, circulatory organ system, digestive system). As a result of examination with added information from the new source, the classification results were changed from the previous classification.

[Evidence Data]
(1) This substance is an antibiotic used as an ethical pharmaceutical. It has been reported that serious side effects are aplastic anemia, gray syndrome, and optic or peripheral neuritis, and other side effects are effects on the blood (granulocytopenia, thrombocytopenia), effects on the digestive organs (tightness in the stomach, nausea, vomiting, loose stool, diarrhea, enteritis), hypersensitivity, microbial substitution, and vitamin deficiency (JAPIC Ethical Pharmaceuticals 2017 (2016)).
(2) Hematological toxicity effects of this substance have been observed in humans. One effect is dose-related, reversible myelosuppression that usually occurs. This effect is enhanced during administration, but it regresses once the administration is withdrawn. The other effect is serious aplastic anemia, which is not dose-related and often irreversible (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(3) It is clear that, when the dosage of this substance exceeds 4 g/day in humans, the incidence of dose-related myelosuppression increases. Toxicity is reversible if the dose is not sustained or the dose is decreased (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(4) This substance is known to be related to the development of Gray Syndrome (or Gray Baby Syndrome). Gray syndrome is a state of cardiovascular collapse that usually appears 2 to 9 days after the start of administration of this substance. The characteristic symptoms are an inability to eat, vomiting, distended abdomen, cyanosis, lethargy, a state of shock, lower body temperature, etc. It is also said to cause death in 60% of cases, and it usually appears when the dosage of this substance exceeds 25 mg/kg bw/day (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(5) When therapeutic doses of this substance were orally administered for a long term, bleeding was induced. This was caused by myelosuppression or inhibition of synthesis of vitamin K due to weakening of intestinal bacterial flora that produces vitamin K (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(6) Several cases of toxicity to the eyes due to long-term administration of this substance was reported. This toxicity to the eyes was often optic neuritis with scotoma and weaker eyesight, and in some cases, retrobulbar neuritis was observed. Retrobulbar neuritis was observed in cases of cystic fibrosis. This might be because this substance was used for treatment of cystic fibrosis rather than patients having cystic fibrosis were specifically susceptible to retrobulbar neuritis. Total dose in the range from 80 to 250 g was often administered for several months. One patient who was given this substance for 6 weeks (6 g/day; total dose of about 250 g) developed posterior bilateral optic neuritis. There was a possibility that peripheral neuritis was associated with effects on the eyes (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
(7) After administration of this substance, hearing loss might occur. In one case, a 2.5-year-old boy who was dosed with this substance for 26 days (125 mg/kg/day) had difficulty in hearing, and the symptom continued even after administration was stopped. No other medicine was administered (Risk Assessment Report (Veterinary Medicinal Products) (Food Safety Commission of Japan, 2014)).
10 Aspiration hazard Classification not possible
-
-
- - [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 72-hour EC50 = 0.78 mg/L for algae (Desmodesmus subspicatus) (HSDB, 2020). The classification result was changed from the previous classification by reviewing information.
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. The classification result was revised from the previous classification by changes in the classification result for acute toxicity and how to classify it for chronic toxicity.
12 Hazardous to the ozone layer Classification not possible
-
-
- - This substance is not listed in the Annexes to the Montreal Protocol.


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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