NITE - Chemical Management Field

Latest GHS Classification Results by the Japanese Government (edited by NITE)

GENERAL INFORMATION

Item	Information
CAS RN	58-08-2
Chemical Name	caffeine
Substance ID	m-nite-58-08-2_v1
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	To Guidance List
UN GHS document (External link)	To UN GHS document
FAQ（GHS classification results by the Japanese Government）	To FAQ
List of Information Sources (Excel file)	List of Information Sources
List of Definitions/Abbreviations	Definitions/Abbreviations
Sample Label by MHLW (External link)	MHLW Website (in Japanese Only)
Sample SDS by MHLW (External link)	MHLW Website (in Japanese Only)
OECD/eChemPortal (External link)	To OECD/eChemPortal (External link)

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecules.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
7	Flammable solids	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Pyrophoric solids	Not classified	- -	-	-	Its autoignition point is 540degC (IUCLID (2000)), which is above 70degC.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
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).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance contains oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
16	Corrosive to metals	Classification not possible	- -	-	-	Test methods applicable to solid substances are not available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
17	Desensitized explosives	-	- -	-	-	-	-	-

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
1	Acute toxicity (Oral)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	Since its twelve LD50 values for rats (261 - 383, 200 - 400, 192, 483, 233, 355, 247, 344, 421, 700, 50 - 500, and 261 - 383 mg/kg) have been reported in List 1 literature, and seven of them are within the guidance values of Category 3 and five Category 4 (SIDS (accessed in September 2008)), the substance was classified into Category 3.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Dermal)	Not classified	- -	-	-	Since in a dermal test for 24 hours using rats, its LD50 > 2000 mg/kg (SIDS (accessed in September 2008)), the substance was classified into "Not classified" in JIS classification (Category 5 or Not classified in UN classification).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Gases)	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
1	Acute toxicity (Inhalation: Dusts and mists)	Category 4	Warning	H332	P304+P340 P261 P271 P312	Since in an inhalation test for four hours using rats, its LC50 = 4.94 mg/L, about 4.94 mg/L (males), about 4.1 mg/L (females) (SIDS (accessed in September 2008)), the substance was classified into Category 4. As relevant information, since the LC50 values were above its saturated vapour pressure concentration, the substance was considered as dust.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
2	Skin corrosion/irritation	Not classified	- -	-	-	Since in a test using rabbits (OECD TG 404), the substance in a 50% aqueous dilution was not irritating to the skin of rabbits (irritation index was 0) (SIDS (accessed in September 2008)), it was classified into "Not classified".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
3	Serious eye damage/eye irritation	Not classified	- -	-	-	In an irritation test using rabbits (OECD TG 405), the substance was not irritating to the eyes of rabbits. Mean irritation indices were 0.9 (corneal opacity), 0 (iritis), 1.6 (conjunctival erythema), and 0.6 (conjunctival edema). The strongest signs of irritation were observed in all 3 animals within the first 24 hours. By day 8 only one animal showed slight corneal opacity and conjunctival redness (SIDS (accessed in September 2008)). Therefore, the substance was classified into "Not classified".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Respiratory sensitization	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
4	Skin sensitization	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
5	Germ cell mutagenicity	Not classified	- -	-	-	In a micronucleus test with oral administration using mice and Chinese hamsters (in vivo mutagenicity test using somatic cells), only the highest dose (in the range of the LD50) caused an induction of micronuclei (SIDS (accessed in September 2008)). The substance was negative in another micronucleus test using mice and Chinese hamsters, a chromasomal aberration test using human lymphocytes and rat blood cells (somatic cell in vivo mutagenicity test), a chromasomal aberration test using mouse testis cells and oocytes (SIDS (accessed in September 2008)). Furthermore, in a rat dominant lethal test (in vivo multi-generation mutagenicity test), preimplantation loss or depression of female fertility attributable to the test substance was observed, and the study was negative (SIDS (accessed in September 2008)). Therefore, the substance was classified into "Not classified". As relevant information, in in-vivo genotoxicity tests, it is reported that a single oral dose did not induce unscheduled DNA synthesis in pancreatic cells from rats, and in sister chromatid exchange tests using mice and Chinese hamsters, no increase in SCE was seen (SIDS (accessed in September 2008)). In in vitro mutagenicity tests, it is reported that the substance was negative in an Ames test and in mouse and human lymphocyte tests, but was positive in a chromosomal aberration test using hamsters in the absence of metabolic activation (SIDS (accessed in September 2008)).	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
6	Carcinogenicity	Not classified	- -	-	-	In 78 week and 104 week oral administration tests using rats, there were no differences between control and treated animals for tumor incidences (SIDS (accessed in September 2008)). In a series of experiments, female mice orally received the substance for 43 weeks. Neither the incidence of mammary carcinomas nor mean time to tumor appearance were significantly affected; however, the number of mammary adenocarcinomas had significantly increased among those given 500 mg/L (HSDB (2006)). Furthermore, the substance is rated Group 3 in IARC. Therefore, the substance was classified into "Not classified".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
7	Reproductive toxicity	Category 1A	Danger	H360	P308+P313 P201 P202 P280 P405 P501	In a reproductive test using rats that underwent oral administration, no significant difference in birth rate, birth number, survival rate, or sex ratio of the offspring was noted, but the motility and velocity of sperm were slightly decreased and average radius was decreased in parental animals (SIDS (accessed in September 2008)). In addition, in a mouse reproductive test with oral administration, there were significant differences between control and treated animals for offspring birth number, survival rate, and body weight reduction. Therefore, slight reproductive toxicity was suggested. While, in a developmental toxicity test with oral administration to rats and mice during the organogenetic period, no developmental toxicity was observed (SIDS (accessed in September 2008)). In humans, there are many epidemiological reports on reduced body weights of neonates, abortion and stillbirth, delayed conception, and reduced fertility (Birth Defects (3rd, 2000)). And in a mouse reproductive test, there were significant differences between control and treated animals for offspring birth number and survival rate. Accordingly, its reproductive toxicity in humans was considered, and the substance was classified into Category 1A.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
8	Specific target organ toxicity - Single exposure	Classification not possible	- -	-	-	Although it is documented that after ingestion of 27 g of caffeine in a suicide attempt, a woman developed recurrent cardiac arrest, seizure activity, and myoclonic jerks (HSDB (2006)), classification is not possible only on these data, and there is no other data available. Therefore, due to the lack of data, the substance was classified into "Classification not possible".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
9	Specific target organ toxicity - Repeated exposure	Classification not possible	- -	-	-	In a 90-day oral toxicity study (in drinking water, 188, 375, 750, 1500, 3000 ppm; male, 19.7, 42, 85.4, 151, 272 mg/kg bw/day; female, 23, 51, 104, 174, 287 mg/kg bw/day), at doses up to 1500 ppm/day (male, 151 mg/kg bw/day; female, 174 mg/kg bw/day) equivalent to the guidance value of Category 2, no marked changes in clinical signs of toxicity were observed. With one exception (dose-dependent cellular enlargement in salivary gland), no pronounced significant changes were observed (SIDS (accessed in September 2008)). In addition, the NOAEL = 151 mg/kg/day (SIDS (accessed in September 2008)), which is above the guidance value of Category 2. Accordingly, the substance should be classified in "Not classified" (oral). However, since there is no information available on other routes, the substance was classified into "Classification not possible".	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
10	Aspiration hazard	Classification not possible	- -	-	-	No data available.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification	Classification year (FY)	GHS Classification Guidance for the Japanese Government
11	Hazardous to the aquatic environment Short term (Acute)	Category 3	- -	H402	P273 P501	Based on its 96h-LC50 = 87 mg/L for fish (golden orfe) (SIDS, 2002), the substance was classified into Category 3.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
11	Hazardous to the aquatic environment Long term (Chronic)	Category 3	- -	H412	P273 P501	Since its preexisting classification for acute toxicity is Category 3, and it is not rapidly degradable (SRC, BioWin V4.10), the substance was classified into Category 3.	FY2008	GHS Classification Guidance by the Japanese Government （Sep, 2008）
12	Hazardous to the ozone layer	-	- -	-	-	-	-	-

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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