GHS Classification Result

Chemical Name:gamma-Butyrolactone
CAS:96-48-0

Result:
ID: 22A4075
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 - - - - Liquid (GHS definition)
3 Aerosols Not applicable - - - - Not aerosol products.
4 Oxidizing gases Not applicable - - - - Liquid (GHS definition)
5 Gases under pressure Not applicable - - - - Liquid (GHS definition)
6 Flammable liquids Not classified - - - - Its flash point reported 98 degC (closed-cup) (ICSC (J) (2000)) is >= 93 degC.
7 Flammable solids Not applicable - - - - Liquid (GHS definition)
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 classified - - - - Since its autoignition temperature is 455 degC (ICSC (2000)), it is considered that the substance does not ignite at room temperature.
10 Pyrophoric solids Not applicable - - - - Liquid (GHS definition)
11 Self-heating substances and mixtures Classification not possible - - - - Test methods applicable to liquid substances are not 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 - - - - The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen.
14 Oxidizing solids Not applicable - - - - Liquid (GHS definition)
15 Organic peroxides Not applicable - - - - Organic compounds containing no bivalent -O-O- structure.
16 Corrosive to metals Classification not possible - - - - No data 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 values of 800 - 1600 mg/kg (IARC 11 (1976)) and 1800 mg/kg (NTP TR 406 (1992)), the substance was classified into Category 4.
1 Acute toxicity (Dermal) Not classified - - - - Based on the guinea pig LD50 value of approximately 5600 mg/kg (IARC 11 (1976)), the substance was classified as "Not classified".
1 Acute toxicity (Inhalation: Gases) Not applicable - - - - Liquid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Classification not possible - - - - No data available.
1 Acute toxicity (Inhalation: Dusts and mists) Not classified - - - - Based on the results of the study in rats (GLP-compliant) that exposure of 5.1 mg/L caused no mortality and the LC50 value of > 5.1 mg/L (IUCLID (2000)), the substance was classified as "Not classified". Since the test concentration (5.1 mg/L) was higher than the saturated vapor pressure concentration (2.08 mg/L), the criterion values for mist were adopted.
2 Skin corrosion/irritation Not classified - - - - In the rabbit test, application of undiluted substance for 20 hours caused no irritating effects (HSDB (2008)). In other rabbit test, slightly, hardly perceptible or moderate erythema and hardly perceptible edema occurred and resulted as "mildly irritating" (HSDB (2008)). Based on the information, the substance was classified as "Not classified" in the JIS classification (corresponding to Category 3 in the UN-GHS classification). As relevant notes, application of undiluted technical-grade of the test substance to rabbits caused moderate to severe erythema with edema in 3 of 4 animals, and one animal revealed apparent erythema without edema formation after 72 hours of application. Therefore, test substance was concluded as moderate to severe irritating to the skin (HSDB (2008)).
3 Serious eye damage/eye irritation Category 2A Warning H319: Causes serious eye irritation P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing.
P337+P313: If eye irritation persists: Get medical advice/attention.
P264: Wash ... thoroughly after handling.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
In several reports of rabbit tests, there was only one information of the study in conformity with OECD TG 405 and GLP from the "List 1" information source designated in the GHS classification guidance for the Japanese government. The substance was classified as Category 2A based on the report in which the modified maximum average score (MMAS) was 43.9 (maximum score was 110) equivalent to AOI 30 - 80 (ECETOC TR 48 (1998)). In other rabbit tests, some results were reported as follows: irritation effects containing inflammatory irritation and slight corneal opacity (HSDB (2008)), corrosive effects containing severe irritation with conjunctive necrosis, radial damage, corneal opacity and ulceration (HSDB (2008)) and irritation of the conjunctiva, iris and cornea and recovery within 7 days after treatment in 5 of 6 animals (HSDB (2008)).
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - In the guinea pig test, skin sensitization was not evident (KemI-Riskline (2004)), however, details of test methods and results were not reported. Therefore, the substance was classified as "Classification not possible".
5 Germ cell mutagenicity Not classified - - - - The classification was concluded as "Not classified" due to negative results in both of two micronucleus test data using bone marrow cells obtained from the mice intraperitoneally administered (in vivo mutagenicity test in somatic cells) (IARC 71 (1999)). As relevant information, as for in vitro studies, negative results in the Ames test (IARC 71 (1999)) and positive results in the chromosome aberration test using Chinese hamster ovary cells (NTP DB (Access on Jul. 2010)) were reported.
6 Carcinogenicity Classification not possible - - - - The classification was concluded as "Classification not possible" based on the criterion of "Group 3" by the IARC carcinogenicity assessment (IARC suppl. 7 (1987)). As relevant information, in the 2-year oral administration study in rats and mice, as for rats, no evidence of carcinogenicity of the substance was noted because no increase in the incidence of neoplastic lesions associated with the administration in both sexes was observed. As for mice, ambiguous evidence of carcinogenicity was shown because the incidences of hyperplasia and pheochromocytoma of the adrenal medulla slightly increased in males at low dose, but no evidence of carcinogenicity in females (NTP TR 406 (1992)).
7 Reproductive toxicity Classification not possible - - - - In the oral administration study using pregnant rats during the organogenetic period, no embryotoxicity were seen (NTP TR 406 (1992)). In the inhalation study using pregnant rabbits during the organogenetic period (OECD TG 414, GLP-compliant), no signs of maternal toxicity and embryotoxicity were observed, and there was no evidence of treatment-related teratogenicity (IUCLID (2000)). However, because no information was provided regarding sexual functions and fertility of parental animals, the substance was classified as "Classification not possible".
8 Specific target organ toxicity - Single exposure Category 2 (central nervous system), Category 3 (narcotic effects) Warning H371: May cause damage to organs (central nervous system)
H336: May cause drowsiness or dizziness (narcotic effects)
P309+P311: IF exposed or if you feel unwell: 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.
P405: Store locked up.
P501: Dispose of contents/container to ...
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P403+P233: Store in a well-ventilated place. Keep container tightly closed.
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.
As for acute toxic effects based on human cases, the following symptoms were described: bradycardia, hypothermia, depression of central nervous system, prolonged unconsciousness, confusion, aggression, torpor, and ataxia (KemI-Riskline (2004)). In fact, unconsciousness was reported in numerous cases who ingested the substance or its products, and the signs concurrently observed included coma, narcosis, convulsions and hypopnea (KemI-Riskline (2004), HSDB (2000)). In the animal study, signs of sedation and loss of righting reflex were described in rats (LD50 value: 1800 mg/kg) following single oral administration (NTP TR 406 (1992)). With regard to the results described above, since information on humans were collected from the "List 2" information source designated in the GHS classification guidance for the Japanese government and the findings of rats corresponded to Category 2 within the range of the guidance values, the substance was classified as Category 2 (central nervous system). Moreover, narcotic effects were also described, so that Category 3 (narcotic effects) was added.
9 Specific target organ toxicity - Repeated exposure Classification not possible - - - - In the 13-week repeated oral dose studies in rats and mice, deaths occurred at the highest dose level in both species (900 mg/kg/day for rats, 1050 mg/kg/day for mice), suppression of body weight gain and lateral position were found in rats at 450 mg/kg/day or higher, and in mice at 525 mg/kg/day or higher. No toxic effects were seen in rats at 225 mg/kg/day and in mice at 262 mg/kg/day, except for slight to moderate inactivity (NTP TR 406 (1992)). In addition, the NOEL values in the 90-day feeding studies in both rats and dogs were reported as 0.8% (400 mg/kg/day) that exceeded the range of the guidance values (IUCLID, 2000). According to these documents, the classification is considered as equivalent to "Not classified" category in oral route. However, since no sufficient data was available for the other routes (inhalation, dermal), the classification for specific target organ toxicity (repeated exposure) was concluded as "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) Not classified - - - - Classified as "Not classified" since all LC50 and EC50 values exceeded 100 mg/L in acute toxicity tests for fish, crustacea and algae (IUCLID, 2000).
11 Hazardous to the aquatic environment (Long-term) Not classified - - - - Classified as "Not classified" since its acute toxicity is "Not Classified" and it is not non-water soluble (water solubility = 1000 g/L (PHYSPROP Database, 2011)).
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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