GHS Classification Result

Chemical Name：caffeine
CAS：58-08-2

Result：
ID: 20A2140
Classifier: Ministry of Health, Labour and Welfare （MHLW）, Ministry of the Environment （MOE）
Year Classified: FY2008
Reference Manual: GHS Classification Guidance by the Japanese Government （Sep, 2008）

PHYSICAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Explosives Not applicable - - - - There are no chemical groups associated with explosive properties present in the molecules.
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 solid 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 Not classified - - - - Its autoignition point is 540degC (IUCLID (2000)), which is above 70degC.
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 contains oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
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.

HEALTH HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Acute toxicity （Oral） Category 3 Danger H301: Toxic if swallowed P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment （see ... on this label）.
P330: Rinse mouth.
P405: Store locked up.
P501: Dispose of contents/container to ... 		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.
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).
1 Acute toxicity （Inhalation: Gases） Not applicable - - - - Solid (GHS definition)
1 Acute toxicity （Inhalation: Vapours） Classification not possible - - - - No data available.
1 Acute toxicity （Inhalation: Dusts and mists） Category 4 Warning H332: Harmful if inhaled P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P261: Avoid breathing dust/fume/gas/mist/vapours/spray.
P271: Use only outdoors or in a well-ventilated area.
P312: Call a POISON CENTER or doctor/physician if you feel unwell. 		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.
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".
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".
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - No data available.
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)).
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".
7 Reproductive toxicity Category 1A Danger H360: May damage fertility or the unborn child P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ... 		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.
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".
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".
10 Aspiration hazard Classification not possible - - - - No data available.

ENVIRONMENTAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
11 Hazardous to the aquatic environment （Acute） Category 3 - - H402: Harmful to aquatic life P273: Avoid release to the environment.
P501: Dispose of contents/container to ... 		Based on its 96h-LC50 = 87 mg/L for fish (golden orfe) (SIDS, 2002), the substance was classified into Category 3.
11 Hazardous to the aquatic environment （Long-term） Category 3 - - H412: Harmful to aquatic life with long lasting effects P273: Avoid release to the environment.
P501: Dispose of contents/container to ... 		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.


NOTE:
* 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.

Reference：
Reference Manual
Definitions / Abbreviations
Model Label by MHLW

 MHLW Website （in Japanese Only）
Model SDS by MHLW

 MHLW Website （in Japanese Only）

To GHS Information