GHS Classification Result

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GENERAL INFORMATION
Item Information
CAS RN 109-99-9
Chemical Name Tetrahydrofuran
Substance ID H26-B-068, R-027
Classification year (FY) FY2014
Ministry who conducted the classification Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised Revised
Classification result in other fiscal year FY2006  
Download of Excel format Excel file

REFERENCE INFORMATION
Item Information
Guidance used for the classification (External link) GHS Classification Guidance for the Japanese Government (FY2013 revised edition)
UN GHS document (External link) UN GHS document
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
Signal word
Hazard statement
(code)
Precautionary statement
(code)
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 Category 2


Danger
H225 P303+P361+P353
P370+P378
P403+P235
P210
P233
P240
P241
P242
P243
P280
P501
It was classified in Category 2 based on a flash point of -14.5 deg C (Closed cup) and a boiling point of 66 deg C (ICSC (1997)).
Besides, it is classified in Class 3, PG II (UN2056) in UNRTDG.
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
-
-
- - It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 321 deg C (ICSC (1997)).
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 in the molecule
16 Corrosive to metals Classification not possible
-
-
- - No data available.

HEALTH HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
1 Acute toxicity (Oral) Category 4


Warning
H302 P301+P312
P362+P364
P264
P270
P330
P501
There are 5 reports of LD50 values of 1,650 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006)), 1,900 mg/kg (NTP TR475 (1998)), 2,000 mg/kg (14-day-old), 3,200 mg/kg (young adult), and 2,800 mg/kg (mature) (IRIS TR (2012), ACGIH (7th, 2005)) for rats. According to the GHS Classification Guidance for the Japanese Government, it was classified in Category 4 to which the largest number of data (3) corresponds.
1 Acute toxicity (Dermal) Classification not possible
-
-
- - Classification not possible due to lack of data.
1 Acute toxicity (Inhalation: Gases) Not applicable
-
-
- - Liquid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Category 4


Warning
H332 P304+P340
P261
P271
P312
Based on a report of an LC50 value (3 hours) of 21,000 ppm for rats (converted 4-hour equivalent value: 18,187 ppm) (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ACGIH (7th, 2005), NTP TR475 (1998)), it was classified in Category 4. Besides, the LC50 value is lower than 90% of the saturated vapour concentration (213,158 ppm), the reference value in units of ppm was applied as a vapour without a mist. New high-priority information sources (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ACGIH (7th, 2005), NTP TR475 (1998)) were added to replace low-priority information sources, and the category was revised.
1 Acute toxicity (Inhalation: Dusts and mists) Classification not possible
-
-
- - Classification not possible due to lack of data.
2 Skin corrosion/irritation Not classified
-
-
- - There are reports that the primary irritation score was 1.93 in a skin irritation test with rabbits (ACGIH (7th, 2005)), and that it was irritating in another test with rabbits (IUCLID (2000)). In addition, as for effects on humans, there is a description that the vapour of this substance is irritating to the skin (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ACGIH (7th, 2005)). Moreover, there are multiple conflicting reports of "irritating" and "not irritating" (IUCLID (2000)). From the above results, considering the possibility of mild irritation, it was classified as "Not classified" (Category 3 in UN GHS classification). The information in List 1 was added, and the category was changed.
3 Serious eye damage/eye irritation Category 2A


Warning
H319 P305+P351+P338
P337+P313
P264
P280
There is a report that it was moderately irritating in an eye irritation test in which 0.1 mL of this substance was applied to rabbits (ACGIH (7th, 2005)). Additionally, as for effects in humans, there are reports that the vapour of this substance is irritating to the eyes (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006)), and that the liquid of this substance is severely irritating to the eyes (HSDB (Access on July 2014)). From the above, based on descriptions of "moderately irritating" and "severely irritating," it was classified in Category 2A.
4 Respiratory sensitization Classification not possible
-
-
- - Classification not possible due to lack of data.
4 Skin sensitization Classification not possible
-
-
- - Classification not possible due to lack of data. Besides, although there is a report that it was negative in sensitization in humans (IUCLID (2000)), these data were judged as insufficient for use for the classification since the details such as test methods are unknown.
5 Germ cell mutagenicity Classification not possible
-
-
- - The substance was classified as "Classification not possible" because it was not possible to classify a substance as "Not classified" according to the revised GHS classification guidance for the Japanese government. As for in vivo, it was negative in micronucleus tests with bone marrow erythrocytes and peripheral blood erythrocytes of mice, and negative in a mouse bone marrow chromosomal aberration test, and negative in an unscheduled DNA synthesis test with rat liver (ACGIH (7th, 2005), NTP DB (Access on September 2014), IUCLID (2000)). As for in vitro, it was negative in bacterial reverse mutation tests, a chromosome aberration test, a micronucleus test and a sister chromatid exchange test with cultured mammalian cells (ACGIH (7th, 2005), NTP DB (Access on September 2014), IUCLID (2000)).
6 Carcinogenicity Category 2


Warning
H351 P308+P313
P201
P202
P280
P405
P501
It is classified in A3 by ACGIH (ACGIH (7th, 2005), HSDB (Access on August 2014)), and as "suggestive evidence of carcinogenic potential" by EPA (IRIS TR (2012)). From the above, it was classified in Category 2.
7 Reproductive toxicity Category 2


Warning
H361 P308+P313
P201
P202
P280
P405
P501
In a two-generation reproduction study (OECD TG416) with rats by the oral route (drinking water), at a dose (9,000 ppm) where parental toxicity (decreased body weight gain, increased relative kidney weight) was observed, although no effects on reproductive function were observed, decreased pup body weight gain and delayed eye opening were observed during lactation period. However, there is a report that no teratogenicity was observed (IRIS TR (2012), Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), IUCLID (2000)). Since the effects observed in pups in this test were slight, it was not used for classification.
There is a report that in a teratogenicity test with rats by the inhalation route, at a dose (5,000 ppm) where decreased body weight gain was observed in maternal animals, slight effects (decreased pup body weight, delayed ossification) were observed in the fetuses (IRIS TR (2012), Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006)). Since the effect observed in pups in this test was slight, it was not used for classification.
In a teratogenicity test with mice by the inhalation route, resorption was observed in 95% at a dose (5,000 ppm) where maternal toxicity (more than 25% died) was observed. Since serious maternal toxicity was observed, this finding was not used for classification. However, there is a report that effects (reduction in the percent live pups, delayed ossification of the sternum) were observed in the fetuses at a dose (1,800 ppm) where decreased body weight gain and narcotic effects were observed in maternal animals (IRIS TR (2012), Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006)).
As above, no effects on fertility and no teratogenicity were observed, but because a reduction in the percent live pups was observed at the dose where maternal toxicity was observed in the teratogenicity test with mice, it was classified in Category 2.
8 Specific target organ toxicity - Single exposure Category 1 (central nervous system), Category 3 (respiratory tract irritation, narcotic effects)



Danger
Warning
H370
H335
H336
P308+P311
P260
P264
P270
P321
P405
P501
P304+P340
P403+P233
P261
P271
P312
This substance is irritating to the respiratory tract (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006), ACGIH (7th, 2005), HSDB (Access on August 2014)). In humans, by the inhalation exposure to the vapor, it may affect the central nervous system and cause lethargy. Additionally, cough, sore throat, dizziness, headache, nausea and loss of consciousness develop due to oral ingestion or inhalation exposure (Environmental Risk Assessment for Chemical Substances Vol.5, Tentative Hazard Assessment Sheet (Ministry of the Environment, 2006)). Moreover, elevated hepatic enzymes in the blood, nausea, dizziness, hypoacusia, angioedema, occipital headache and cerebral convulsions are reported (ACGIH (7th, 2005)).
As for experimental animals, by inhalation exposure with mice or rats, narcotic effects, hyperpnea, hypertension, salivation, lethargy, abnormal gait, loss of righting reflex, reduced motor activity, nasal cavity bleeding, muscle spasms, effect on the central nervous system, dyspnea, ataxia, cyanosis, coma, the inhibition of propagation and maintenance of electrical-evoked seizure discharge are reported (OEL Documentations (Japan Society For Occupational Health (JSOH), 1978), ACGIH (7th, 2005), HSDB (Access on August 2014)).
From the above, it was considered to have effects on the central nervous system, respiratory tract irritation and narcotic effects in humans, it was classified in Category 1 (central nervous system), Category 3 (respiratory tract irritation, narcotic effects). Besides, although narcotic effects were not adopted in the previous classification, since narcotic effects in mice and rats were seen in the ACGIH and the OEL Documentations (Japan Society For Occupational Health (JSOH)), it was adopted this time.
9 Specific target organ toxicity - Repeated exposure Category 1 (central nervous system, respiratory organs, liver)


Danger
H372 P260
P264
P270
P314
P501
As for findings by repeated exposure in humans, there are many reports by occupational exposure. And there are reports of central nervous system symptoms (headache, dizziness, nausea), respiratory organs symptoms (cough, chest pain, dyspnea), liver damage (elevated serum AST, ALT and gamma-GT, fatty change in the tissue and siderosis in the liver biopsy) (IRIS TR (2012), ACGIH (7th, 2005)). However, all of these are effects of combined exposure to several other solvents, and the relationship between concentration and exposure period is also unclear. In workplace environment monitoring for occupational exposure by NIOSH, in the interviews with workers in a plant where several solvents (acetone, toluene, methyl ethyl ketone) including this substance were detected, there is a report that there were many complaints such as irritation to the eyes and respiratory organs, headache, consciousness disturbed and lethargy (IRIS TR (2012)). In addition, there is a description that many workers exposed to this substance at up to concentrations of 1,000 ppm (2,950 mg/m3) in a PVC pipe manufacturing plant complained of fatigue in the lower body, and in a clinical test, decreased specific gravity of whole blood, decreased leukocyte count, increased serum ALT activity, palpable liver enlargement, and hypotension were observed (IRIS TR (2012)). Besides, there is also a report that hematuria was shown in a worker exposed to this substance, and a biopsy revealed IgA-proliferative glomerulonephritis (IRIS TR (2012), ACGIH (7th, 2005)). However, only one case was reported. As for experimental animals, there is a description that in a test in which rats were exposed to this substance (estimated as vapour) by inhalation for 12 weeks (4 hours/day), at a concentration (200 ppm (600 mg/m3): converted guidance value: 0.37 mg/L/6 hours) corresponding to Category 2, increased serum AST was observed. Additionally, there are descriptions that in NTP tests in which rats and mice were exposed by inhalation for 13 weeks or 2 years, at high concentrations (1.77-5.31 mg/L/6 hours) corresponding to "Not classified," effects on the liver (increased weight, hepatic necrosis) and central nervous system symptoms (coma (narcotic effects) observed during and up to 1 hour after cessation of exposure, ataxia) were observed. From the above descriptions, it was considered that the target organs in experimental animals were also the liver and central nervous system. Besides, effects on the "hemal system" were observed at extremely high concentrations in some tests also with experimental animals. However, effects on the hemal system are less common even in the findings in humans, so it was judged to be exceptional findings. Moreover, since findings to suspect "kidney" as a target organ were not obtained from animal tests, cases of nephritis in humans were judged to be peculiar cases. From the above, the findings on occupational exposure in humans are not necessarily the effects due to exposure to this substance alone. However, it was classified in Category 1 (central nervous system, respiratory organs, liver), judging in conjunction with the results on experimental animals. Besides, "kidney" in the previous classification was deleted due to the above reason, and "respiratory organs" with high commonality in human findings were added this time.
10 Aspiration hazard Classification not possible
-
-
- - Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS
Hazard class Classification Pictogram
Signal word
Hazard statement
(code)
Precautionary statement
(code)
Rationale for the classification
11 Hazardous to the aquatic environment (Acute) Not classified
-
-
- - It was classified as "Not classified" from 96-hour LC50 = 2160 mg/L for fish (Pimephales promelas) (ECETOC TR91, 2003).
11 Hazardous to the aquatic environment (Long-term) Not classified
-
-
- - If chronic toxicity data are used, then it is classified as "Not classified" due to rapid degradability (a degradation rate by BOD: 100% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1975)), and 35-38-day NOEC = 216 mg/L for fish (Pimephales promelas) (Environmental Risk Assessment for Chemical Substances Vol. 7 (Ministry of the Environment, 2009)).
If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified as "Not classified" from 48-hour EC50 = 5930 mg/L for crustacea (Daphnia magna) (Environmental Risk Assessment for Chemical Substances Vol. 7 (Ministry of the Environment, 2009)), and being not water-insoluble (water solubility = 1000000 mg/L, PHYSPROP Database, 2009).
From the above results, it was classified as "Not classified."
12 Hazardous to the ozone layer Classification not possible
-
-
- - This substance is not listed in the Annexes to the Montreal Protocol.


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.

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