GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 633-65-8 |
| Chemical Name | Berberine hydrochloride |
| Substance ID | H29-A-023 |
| Classification year (FY) | FY2017 |
| Ministry who conducted the classification | Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE) |
| New/Revised | New |
| Classification result in other fiscal year | |
| 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) | |
| Model SDS by MHLW (External link) | |
| OECD/eChemPortal (External link) | eChemPortal |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Explosives | Not applicable |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. |
| 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 solids | 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 | 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 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 |
- |
- | - | The substance is an organic compound containing chlorine which is ionically bonded to the element other than carbon or hydrogen (N) but does not contribute to oxidation. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to solid substances are not available. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 1 | Acute toxicity (Dermal) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 2 | Skin corrosion/irritation | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 3 | Serious eye damage/eye irritation | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | Since information on berberine chloride (CAS RN 633-65-8), tetrahydroberberine (CAS RN 522-97-4), berberine hydrochloride (CAS RN 633-65-8) was confirmed as information for berberine and berberine compounds, these items of information was used for classification. As for in vivo, berberine chloride and tetrahydroberberine were negative in micronucleus tests with mouse bone marrow cells (NTP DB (Access on August 2017), Iran J Basic Med Sci, Vol. 20, No. 5, May 2017), and they were positive in DNA damage tests with mouse bone marrow cells and cardiac cells (Iran J Basic Med Sci, Vol. 20, No. 5, May 2017). As for in vitro, there were positive and negative results in bacterial reverse mutation tests with berberine chloride, berberine hydrochloride and tetrahydroberberine (NTP DB (Access on August 2017), Iran J Basic Med Sci, Vol. 20, No. 5, May 2017). However, neither the in vivo nor in vitro positive results were reproducible. From the above, it was classified as "Classification not possible" according to the GHS classification guidance for the Japanese government. |
| 6 | Carcinogenicity | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, there are several reports that berberine exhibits antitumor activity in vitro and in vivo (Kamrani Rad, S.Z, et al. IJBMS, 20, 516-529 (2017)). In addition, the root powder of goldenseal which is a plant containing berberine and other alkaloids was carcinogenic to the liver of rats and mice and is classified as Group 2B by IARC (IARC 108 (2016)). |
| 7 | Reproductive toxicity | Category 2 |
 Warning |
H361 |
P308+P313
P201 P202 P280 P405 P501 |
When exposed to Chinese medicines containing berberine via the placenta in the fetal period, or when it is ingested via breast milk or directly in the neonatal period, it has been reported that the incidence of jaundice, kernicterus, and brain damage due to jaundice in newborns was high in China and Singapore (Chan E.: Biol. Neonates, 63, 201-208 (1993)). Experimentally, it was confirmed that based on the results of an in vitro test and an in vivo one with rats, berberine liberates bilirubin from the serum binding protein and the blood bilirubin concentration increases (Chan E.: Biol. Neonates, 63, 201-208 (1993), Bateman, J. et al.: Scot. Med. J., 43, 7-15 (1998)). Neonatal jaundice is suspected to be an effect due to this substance which is a component of Chinese medicines. Therefore, it is considered desirable for pregnant women to avoid using herbs or other Chinese medicines containing a large amount of berberine (Jahnke G.S. et al.: Birth Defects Res., 77, 195-206 (2006), Chan E.: Biol. Neonates, 63, 201-208 (1993)). Besides, with respect to side effects of berberine preparations, in the package insert of berberine sulfate hydrate injection which is indicated for diarrhea, it is stated as follows: the safety of administration during pregnancy has not been established, so it is desirable not to administer to pregnant women or women anticipating pregnancy (Ethical Pharmaceuticals 2017 (2016)). As for experimental animals, in developmental toxicity tests for berberine chloride dihydrate (CAS RN 5956-60-5) administered to pregnant rats or pregnant mice by feeding (up to 1,313 mg/kg/day in rats and up to 1,155 mg/kg/day in mice), or by gavage (at 1,000 mg/kg/day in both rats and mice), at 1000-1313 mg/kg/day where maternal toxicity was observed, fetuses showed no effect or only a minor effect (low body weight) in the tests with rats dosed by feeding or gavage (NTP Abstract for TER98008, TER20102 (Access on September 2017), Jahnke G.S. et al.: Birth Defects Res., 77, 195-206 (2006)). On the other hand, in the test with mice by feeding, an increase in water consumption was found at or above 841 mg/kg/day in maternal animals, and an increase in the number of animals with cleft palate was observed in fetuses without statistically significant difference. In administering by gavage to pregnant mice, dead or urgently slaughtered cases of 7/25 were seen in addition to 4/25 deaths due to administration error at 1,000 mg/kg/day in maternal animals, but other than an increase in water consumption, no effect was observed in surviving animals. In fetuses, only a reduced body weight and no cleft palate was found (NTP Abstract for TER20103, TER99002 (Access on September 2017), Jahnke G.S. et al.: Birth Defects Res., 77, 195-206 (2006)). In addition, ovulated female mice were dosed by intramuscular injection with 100 micrograms of this substance for 2-14 days before and after mating with males, and a decrease in the proportion of blastocysts in fertilized eggs and a decrease in the number of live fetuses on gestation day 18.5 were observed, and a possibility is shown that berberine inhibits embryonic development (Tsunoda, Y. and Kato, Y.: J. Mamm. Ova. Res., 28, 40-46 (2011)). From the above, although there are concerns about the findings in humans as side effects of Chinese herbal medicine containing this substance, the causal relationship with this substance is not necessarily clear, and there is weak evidence of reproductive effects on humans. Additionally, many animal tests gave negative results. Therefore, it was judged as appropriate to classify it in Category 2 for this hazard class. |
| 8 | Specific target organ toxicity - Single exposure | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 9 | Specific target organ toxicity - Repeated exposure | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Classification not possible |
- |
- | - | No data available. |
| 11 | Hazardous to the aquatic environment (Long-term) | Classification not possible |
- |
- | - | No data available. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
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* A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted. * Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement. Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file. * 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. * Codes assigned to each of the hazard statements and codes for each of the precautionary statement are based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations. |