GHS Classification Result

日本語で表示

GENERAL INFORMATION

Item Information
CAS number 147-24-0
Chemical name Diphenhydramine hydrochloride
Substance ID 23A5056
Fiscal year of classification conducted FY2011
Classifier(s) (Ministries) Ministry of Health, Labour and Welfare (MHLW), Ministry of the Environment (MOE)
New/Revised New
Download in Excel format Excel file

REFERENCE INFORMATION

Item Information
Guidance used for classification (External link) Physical Hazards & Health Hazards: GHS Classification Guidance by the Japanese Government (July, 2010)
Environmental Hazards: UN GHS Document (4th revised edition)
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
(Code: symbol)
Signal word
Code
(Hazard statement)
Code
(Precautionary statement)
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 - - - "Solids" according to GHS definition.
3 Aerosols Not applicable - - - Not an aerosol product.
4 Oxidizing gases Not applicable - - - "Solids" according to GHS definition.
5 Gases under pressure Not applicable - - - "Solids" according to GHS definition.
6 Flammable liquids Not applicable - - - "Solids" according to GHS definition.
7 Flammable solids Classification not possible - - - No data.
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 - - - "Solids" according to GHS definition.
10 Pyrophoric solids Classification not possible - - - No data.
11 Self-heating substances and mixtures Classification not possible - - - No data.
12 Substances and mixtures which, in contact with water, emit flammable gases Not applicable - - - Not containing metals or semimetals (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At).
13 Oxidizing liquids Not applicable - - - "Solids" according to GHS definition.
14 Oxidizing solids Not applicable - - - An organic compound that contains oxygen which is not chemically bonded to elements other than carbon.
Besides, it is conceivable that chlorine, which is a chlorine ion ionically bonded to an amine, does not contribute to the oxidation of other substances.
15 Organic peroxides Not applicable - - - An organic compound that does not contain -O-O- structure.
16 Corrosive to metals Classification not possible - - - No established test method suitable for solid substances.

HEALTH HAZARDS

Hazard class Classification Pictogram
(Code: symbol)
Signal word
Code
(Hazard statement)
Code
(Precautionary statement)
Rationale for the classification
1 Acute toxicity (Oral) Category 4

Warning
H302
P301+P312
P264
P270
P330
P501
On the basis of three LD50 values for rats (500, 545, 856 mg/kg bw) (NTP TR355 (1989)), it was classified in Category 4.
1 Acute toxicity (Dermal) Classification not possible - - - No data.
1 Acute toxicity (Inhalation: Gases) Not applicable - - - "Solids" according to GHS definition.
1 Acute toxicity (Inhalation: Vapours) Classification not possible - - - No data.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible - - - No data.
2 Skin corrosion/irritation Classification not possible - - - No data.
3 Serious eye damage/eye irritation Classification not possible - - - No data.
4 Respiratory sensitization Classification not possible - - - No data.
4 Skin sensitization Classification not possible - - - No data.
5 Germ cell mutagenicity Classification not possible - - - The classification is not possible due to no in vivo test data.
Besides, as in vitro tests, both negatives as a result of an Ames test and a mouse lymphoma test, a positive in a chromosomal aberration test using CHO cells in the absence of S9mix (NTP DB (Access on May. 2011)), and a negative in a chromosomal aberration test using human leukocytes or fibroblasts in the absence of S9mix (NTP TR355 (1989)) were reported.
6 Carcinogenicity Classification not possible - - - In a 2-year diet administration test using rats and mice, it was reported that no evidence of carcinogenicity in both male and female but only fatty degeneration in the liver in females of a high dose group were observed in mice, and slightly increased incidences of rare brain tumors (astrocytomas, glioma) and alveolar/bronchiolar tumors in males and slightly increased incidences of pituitary gland adenoma in females observed in rats were equivocal evidence of carcinogenicity. (NTP TR355 (1989)).
Because a clear conclusion on carcinogenicity was not drawn as a result of the above 2-year administration tests in 2 animal species, it was classified as "Classification not possible."
7 Reproductive toxicity Category 2, Additional category: Effects on or via lactation

Warning
H361
H362
P308+P313
P201
P202
P281
P405
P501
P260
P263
P264
P270
In an oral administration test during an organogenetic period or gestational day 11 to 14 in mice, general toxicity such as a decreased weight gain, hyperactivity, and convulsions in maternal animals, together with a dose-dependent tendency to increase an incidence of a cleft palate were observed. (NTP TER 82069 (1983))
Furthermore, it was reported that malformations occurred including a cleft palate, cryptorchid testes, hydronephrosis and so on after intraperitoneal administration to rats on gestational day 10. (NTP TR 355 (1989))
On the other hand, the percentage of mothers whose children had a cleft palate was significantly increased in women who had taken this substance more frequently during the first trimester of pregnancy. (NTP TR 355 (1989))
From the above reports, it was classified in Category 2 as a substance suspected human development toxicity.
On the other hand, the package insert states in the "use in pregnant, parturient or breastfeeding women" that "no dosing this substance to breastfeeding women is desirable, and breastfeeding should be avoided if a patient has no choice but to take the substance" and "coma in an infant through breast milk was observed" (Ethical pharmaceuticals (2010), corresponding to List 1).
Therefore, "additional category: effects on or via lactation" was adopted.
8 Specific target organ toxicity - Single exposure Category 1 (central nervous system)

Danger
H370
P307+P311
P260
P264
P270
P321
P405
P501
There is the information that syndrome of the acute poisoning from an overdose of this substance in humans includes impaired consciousness, hallucinations, excitement, mydriasis, tachycardia, incoordination, convulsions, and so on, and coma may develop, with the patient dying of cardiopulmonary arrest. (NTP TR 355 (1989))
Besides, it is also reported that a child given 25 mg twice developed an acute extrapyramidal motor system disorder. (HSDB (2003))
It is stated that a central excitatory action is the most threatening in acute poisoning caused by histamine antagonists including this substance. (HSDB (2003))
From the above knowledge, it was classified in Category 1 (central nervous system).
Besides, poisoning symptoms in rats or mice observed after oral administration are neuromotor excitements, convulsions, tremor, lethargy, prone positions, and so on. (NTP TR 355 (1989))
9 Specific target organ toxicity - Repeated exposure Category 1 (nervous system), Category 2 (liver)

Danger
Warning
H372
H373
P260
P264
P270
P314
P501
This substance is used as an antihistamine medicine, and neuropsychiatric adverse effects (dizziness, fatigue, nervousness and so on) are listed in the package insert (Ethical pharmaceuticals (2010), corresponding to List 1).
Also, animal tests concluded that administration of 25 to 40 mg/kg/day causes neurogenic reactions from irritability and slight incoordination by oral administration of 40 mg/kg/day in dogs (unknown duration of administration). (NTP TR 355 (1989))
From the above knowleadge, it was classified in Category 1 (nervous system).
On the other hand, cytoplasmic vacuolization or fatty degeneration by fat accumulation in liver were reported at 313 to 2500 ppm (15.6 to 125 mg/kg/day) in a 13-week diet administration test in rats and at 313 ppm (46 to 47 mg/kg/day) in a 103-week diet administration test in mice. (NTP TR 355 (1989))
Besides, an increased incidence of granulomas of the liver were also reported in a 103-week diet administration test in rats. (NTP TR 355 (1989))
From these signs in the liver within a range of Category 2 in Guidance values, it was classified in Category 2 (liver).
10 Aspiration hazard Classification not possible - - - No data.

ENVIRONMENTAL HAZARDS

Hazard class Classification Pictogram
(Code: symbol)
Signal word
Code
(Hazard statement)
Code
(Precautionary statement)
Rationale for the classification
11 Hazardous to the aquatic environment (Acute) Classification not possible - - - No data.
11 Hazardous to the aquatic environment (Long-term) Classification not possible - - - No data.
12 Hazardous to the ozone layer Classification not possible - - - This substance is not listed in Annexes to the Montreal Protocol.


NOTES:
* 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.

Updated date:
  2017/3/17 Addition of Rationale for the classification

List of GHS Classification Results