GHS Classification Result

Chemical Name:Theobromine; 2,6-Dihydroxy-3,7-dimethylpurine
CAS:83-67-0

Result:
ID: 22A4081
Classifier: Ministry of Health, Labour and Welfare (MHLW), Ministry of the Environment (MOE)
Year Classified: FY2010
Reference Manual: GHS Classification Guidance by the Japanese Government (July, 2010)

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 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 oxygen which is chemically bonded only to carbon or hydrogen.
15 Organic peroxides Not applicable - - - - Organic compounds containing no bivalent -O-O- structure.
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 4 Warning H302: Harmful if swallowed P301+P312: IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P330: Rinse mouth.
P501: Dispose of contents/container to ...
Based on the rat LD50 value of 950 mg/kg bw (IARC 51 (1991)), the substance was classified into Category 4.
1 Acute toxicity (Dermal) Classification not possible - - - - No data available.
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) Classification not possible - - - - No data available.
2 Skin corrosion/irritation Classification not possible - - - - No data available.
3 Serious eye damage/eye irritation Classification not possible - - - - No data available.
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - No data available.
5 Germ cell mutagenicity Category 2 Warning H341: Suspected of causing genetic defects 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 ...
The substance was classified as Category 2 based on the positive results in the bone marrow micronucleus test by oral administration to Chinese hamster (in vivo mutagenicity test in somatic cells) (IARC 51 (1991)). As relevant information, negative results in the dominant lethal tests (in vivo inheritable mutagenicity test in germ cells) by oral administration to rats and by intraperitoneal administration to mice (IARC 51 (1991)), negative result in the bone marrow chromosome aberration test (in vivo mutagenicity test in somatic cells) by oral administration to Chinese hamster and positive result in the bone marrow sister chromatid exchange test (in vivo genotoxicity test in somatic cells) by oral administration to Chinese hamster, were reported (IARC 51 (1991)). As for in vitro studies, negative results in the Ames test, positive result in the chromosome aberration test using human lymphocytes but negative using Chinese hamster cells, were reported (IARC 51 (1991)).
6 Carcinogenicity Classification not possible - - - - The classification was concluded as "Classification not possible" because the substance was classified as "Group 3" in the IARC assessment (IARC 51 (1991)).
7 Reproductive toxicity Category 1B 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 the reproductive study in mice by dietary administration from one week before mating, adverse effects were observed in at least one or more reproductive parameters, and the proportion of the number of live birth per pregnant parent was decreased compared with the control group. The cross-over mating trial demonstrated severely impaired fertility in females and an increase in the incidence of abnormal spermatozoa (NTP Report # RACB83073 (1984)). In the intraperitoneal injection study using pregnant mice during the organogenetic period, the increase in the occurrence of malformation such as cleft palate and ectrodactyly was reported. In the oral administration study using rabbits during the organogenetic period, malformations were reported (IARC 51 (1991)). The effects on parental fertility or development of offspring mentioned above were detected in the middle dose group at which the general toxicity to parental animals was not revealed. Therefore, the substance was classified as Category 1B. As relevant information, there was the 3-generation study in rats by oral administration of the substance in cocoa, in which adverse effects on reproduction were not seen (IARC 51 (1991)).
8 Specific target organ toxicity - Single exposure Category 1 (thymus) Danger H370: Causes damage to organs (thymus) P307+P311: IF exposed: Call a POISON CENTER or doctor/physician.
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment (see ... on this label).
P405: Store locked up.
P501: Dispose of contents/container to ...
It was reported that oral administration to rats at the dose range of 250 - 300 mg/kg bw caused complete thymic atrophy and the thymus was identified as the target organ (IARC 51 (1991)). Since the administration dose levels of 250 - 300 mg/kg corresponded to Category 1 of the guidance values, the substance was classified as Category 1 (thymus).
9 Specific target organ toxicity - Repeated exposure Classification not possible - - - - In the 90-day feeding study in rats, the only changes were suppression of body weight gain and reduction in testicular weight at the high dose level (250 mg/kg/day), and no pathological and hematological changes were observed (IARC 51 (1991)). Moreover, it was also reported that severe testicular atrophy was observed in the feeding studies in rats for 28 days and 64 weeks at the dietary concentrations of 0.8% (converted dose level as that of 90-day study: 249 mg/kg/day) and 0.5% (converted dose level as that of 90-day study: 250 mg/kg/day), respectively (IARC 51 (1991)). But, these findings revealed at high doses beyond the range of the guidance values. Thus, the classification category was considered equivalent to the "Not classified" category, however, the classification for specific target organ toxicity (repeated exposure) was concluded as "Classification not possible" due to no data for the other routes.
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) Classification not possible - - - - Classification not possible due to lack of data.
11 Hazardous to the aquatic environment (Long-term) Classification not possible - - - - Classification not possible due to lack of data.
12 Hazardous to the ozone layer Classification not possible - - - - This substance is not listed in Annexes to the Montreal Protocol.


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)


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