GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 10049-04-4 |
| Chemical Name | Chlorine dioxide |
| Substance ID | H27-B-069/C-105B_P |
| Classification year (FY) | FY2015 |
| 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 | FY2014 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 (Ver. 1.1)) |
| 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 |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Explosives | Not applicable |
- |
- | - | Gas (GHS definition) |
| 2 | Flammable gases (including chemically unstable gases) | Not classified |
- |
- | - | There is the information that it is not combustible, but it may explode on heating, sunlight or shock (ICSC (1999)). However, the explosion of this substance by heating or sunlight is decomposition explosion, not explosive combustion associated with oxygen in the air. |
| 3 | Aerosols | Not applicable |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Classification not possible |
- |
- | - | There is the information that it is a strong oxidant (ICSC (1999)), but the classification is not possible due to no data. Besides, tests on oxidizing gases established as ISO-10156:2010 have been conducted only for a few substances, but it is described that oxidizing gases for which measurement has not been performed shall be Ci=40, corresponding to Category 1. However, because this substance is not listed in ISO-10156:2010, it was classified as "Classification not possible." |
| 5 | Gases under pressure | Classification not possible |
- |
- | - | No data available. |
| 6 | Flammable liquids | Not applicable |
- |
- | - | Gas (GHS definition) |
| 7 | Flammable solids | Not applicable |
- |
- | - | Gas (GHS definition) |
| 8 | Self-reactive substances and mixtures | Not applicable |
- |
- | - | Gas (GHS definition) |
| 9 | Pyrophoric liquids | Not applicable |
- |
- | - | Gas (GHS definition) |
| 10 | Pyrophoric solids | Not applicable |
- |
- | - | Gas (GHS definition) |
| 11 | Self-heating substances and mixtures | Not applicable |
- |
- | - | Gas (GHS definition) |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | Not applicable |
- |
- | - | Gas (GHS definition) |
| 13 | Oxidizing liquids | Not applicable |
- |
- | - | Gas (GHS definition) |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | Gas (GHS definition) |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Gas (GHS definition) |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to gas substances are not available. |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 1 | Acute toxicity (Oral) | Not applicable |
- |
- | - | Gas (GHS definition). Besides, there is a report of an LD50 value of 94 mg/kg (OECD TG 401) for rats from a 0.2% solution of this substance (SIDS (2009), CICAD 37 (2002)). |
| 1 | Acute toxicity (Dermal) | Not applicable |
- |
- | - | Gas (GHS definition). Besides, there is a report of an LD50 value of > 2,000 mg/kg when a 5% solution of this substance was occlusively applied to rats for 24 hours (GESTIS (Access on September 2015)). |
| 1 | Acute toxicity (Inhalation: Gases) | Category 1 |
 Danger |
H330 | P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501 |
Based on a report of an LC50 value (4 hours) (OECD TG 403) of 32 ppm for rats (SIDS (2009), CICAD 37 (2002)), it was classified in Category 1. |
| 1 | Acute toxicity (Inhalation: Vapours) | Not applicable |
- |
- | - | Gas (GHS definition) |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Not applicable |
- |
- | - | Gas (GHS definition) |
| 2 | Skin corrosion/irritation | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, while there is a report that irritation was not observed as a result of an application of an aqueous solution containing this substance (9.7-11.4 mg/L) to mice for 48 hours (ATSDR (2004)), there is a report that irritation was observed as a result of an application of this substance (80%) to rabbits for 24 hours (EPA Pesticide (2006)). These reports were not used for the classification because they were from the test at low concentrations or the 24-hour application test. Besides, there is a report that in a skin irritation test (OECD TG 404) with rabbits, irritation was not observed as a result of an application of sodium chlorite (CAS RN: 7758-19-2, 34.5%) which is the sodium salt of this substance (SIDS (2009)). |
| 3 | Serious eye damage/eye irritation | Category 2B |
Warning |
H320 | P305+P351+P338 P337+P313 P264 |
There is a report that in an eye irritation test (OPPTS 870.2400) with rabbits, mild irritation was observed by an application of this substance (EPA Pesticide (2006)). In addition, it was reported that as a result of exposure to the gaseous state of this substance (animal species, unknown), eye discharge was seen (CICAD 37 (2002)), and that eye irritation was observed by a single exposure to a high concentration in humans (CICAD 37 (2002)). Since mild irritation was reported in the eye irritation test with rabbits, it was classified in Category 2B. |
| 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, there is a report that in a sensitization test (OECD TG 406, GLP-compliant) with guinea pigs, as a result of an application of sodium chlorite (CAS RN: 7758-19-2) which is the sodium salt of this substance, no sensitization was observed (SIDS (2009)). |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | As for in vivo, it was negative in dominant lethal tests with rats and mice, positive and negative in mouse bone marrow micronucleus tests, negative in mouse bone marrow chromosomal aberration tests, and negative in a sister chromatid exchange test with mouse bone marrow cells (SIDS (2009), IRIS Summary (2000), IRIS Tox. Review (2000), ATSDR (2004), CICAD 37 (2002), ACGIH (7th, 2001)). As for in vitro, it was positive and negative in bacterial reverse mutation tests, and in mammalian cultured cell systems, it was positive in a mouse lymphoma test, and positive and negative in chromosomal aberration tests (IRIS Summary (2000), IRIS Tox. Review (2000), ATSDR (2004), SIDS (2009), CICAD 37 (2002)). It is concluded in SIDS (2009) that this substance is unlikely to have genotoxic (mutagenic) potential because there are many negative in-vivo results. From the above, it was classified as "Classification not possible" in accordance with the GHS classification guidance for the Japanese government. |
| 6 | Carcinogenicity | Classification not possible |
- |
- | - | No information is available on carcinogenicity in humans. As for experimental animals, in a 2-stage carcinogenicity test, in which after water was disinfected with this substance and concentrated, the water concentrate containing residue of this substance was administered by gavage to mice 3 times/week for 2 weeks, and then TPA (12-tetradecanylphorbal-13-acetate), which is a known carcinogen, was administered for 20 weeks by dermal application, there was no significant increase in the number of skin tumors (SIDS (2009)). In addition, in a carcinogenicity study in which the sodium salt of this substance (sodium chlorite) was administered by drinking water to mice at doses of 250 and 500 mg/L (equivalent to 36 and 71 mg/kg/day) for 80 weeks, an increased incidence of lung adenomas was observed in the high dose group (5/43 (12%) vs control group: 0/35 (0%)), however, it is concluded by the authors and cited in SIDS that sodium chlorite was not carcinogenic in mice because there is no dose correlation, and no malignant tumor was observed (SIDS (2009)). As for classification results for carcinogenicity by other organizations, EPA concluded that the substance corresponded to D (Not classifiable as to human carcinogenicity) according to the 1986 guideline and to CBD (Carcinogenic potential cannot be determined) according to the 1996 guideline (IRIS Summary (2000)), but it has not been classified by other organizations. From the above, it was classified as "Classification not possible" for this hazard class in accordance with the GHS classification guidance for the Japanese government. |
| 7 | Reproductive toxicity | Category 1B, Additional category: Effects on or via lactation |
 Danger |
H360 H362 |
P308+P313 P201 P202 P280 P405 P501 |
It was reported that as a result of retrospective epidemiological studies investigating records of morbidity and mortality in infants born between 1940 and 1955 in several US hospitals, in the group of neighboring hospital patients who ingested tap water contaminated with this substance, the incidence of premature births was significantly higher than in the group of hospital patients who ingested tap water without this substance, but the judgment of premature births was based on doctors' assessments, and lacked objective judgment criteria, and in addition, the incidence of premature births was very different between hospitals. Furthermore, it was reported that since there was no information on the extent of exposure to this substance, and the analysis of confounding factors was also insufficient, it was not possible to draw a conclusion from this result (CICAD 37 (2002)). Other than this, there are no available findings on reproductive effects in humans. On the other hand, as for experimental animals, it was reported that in a one-generation study with rats in which an aqueous solution of this substance was administered by gavage at up to 10 mg/kg/day to males for 8 weeks prior to mating and to females from 2 weeks prior to mating, through mating and gestation period, until the 5th day of lactation, there was no effect on the fertility of the parent animals, and no difference from the control group was found in a litter size, a survival rate until weaning, and weights of reproductive organs at weaning in the pups, and NOAELs for both the parent animals and the pups were 10 mg/kg/day (SIDS (2009), IRIS Tox. Review (2000), CICAD 37 (2002)). However, as for effects of developmental toxicity, in a test in which rats (SD) were given this substance by the oral route (drinking water) from 2 weeks prior to mating to the 21st day after birth when the pups were weaned, at 100 ppm (approximately 14 mg/kg/day), a lower value transition of body weight until weaning, a decrease in locomotor activity, a decrease in cerebellar DNA content at weaning, and a decrease in serum T4 values at weaning were observed in the pups, and the LOAEL for neurobehavioral effects on maternal animals due to exposure to this substance through drinking water was set at 14 mg/kg/day and the NOAEL for them was set at 3 mg/kg/day (SIDS (2009), IRIS Tox. Review (2000) CICAD 37 (2002)). Besides, there is a report that even in a study in which maternal rats of another strain (Long-Evans) was dosed by gavage at 14 mg/kg/day (after parturition, from the day 0 to the day corresponding to the day 21 after the birth of the newborns (at weaning)), and the newborns were observed until the 35th day after birth, a lower value transition of body weight and decreases in the absolute weight, DNA content, and protein content of the cerebrum at weaning and on the 35th day after birth were observed (SIDS (2009), IRIS Tox. Review (2000), CICAD 37 (2002)). From the above, as for the experimental animals, in the rats dosed with the aqueous solution of this substance by the oral route during the period of gestation or lactation, findings suggesting effects on postnatal growth and developmental disorders of the cranial nerve system in the pups were shown, and the possibility of effects via involvement of the endocrine system such as thyroid hormones was assumed (SIDS (2009), ATSDR (2004)). However, it was pointed out in SIDS that the multiple developmental toxicity tests described above were not tests compliant with GLP or guidelines, but tests with a limited protocol; and in a 2-generation reproductive toxicity test with rats on the sodium salt of this substance (sodium chlorite), there was no change in the serum T3 and T4 values in the examination on the 25th day after birth of the F1 pups, and this result contradicted that of the developmental toxicity test on this substance. It was carefully judged that the above developmental toxicity tests could not be treated as key studies (SIDS (2009)). In contrast, in ATSDR, the neurodevelopmental toxicity effects by oral exposure to this substance were emphasized, and in the 2-generation reproductive toxicity test with rats given sodium chlorite by drinking water, which was cited above in SIDS, the reduced responsiveness to auditory startle stimulation (24 days after birth) of F1 pups born from parent animals dosed at the medium dose (6 mg/kg/day) was treated as a developmental neurotoxicity effect, and was used as the basis for calculating the minimum risk level (oral MRL) (ATSDR (2004)). From the above, since exposure to this substance in the period of gestation/lactation may cause neurological developmental disorder in newborns from low dose, it was classified in Category 1B for this hazard class, and "additional category for effects on or via lactation" was added. |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (respiratory organs), Category 3 (narcotic effects) |
 Danger Warning |
H370 H336 |
P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312 |
This substance is a corrosive gas and is irritating to the respiratory tract (SIDS (2009), ACGIH (7th, 2001), ATSDR (2004), CICAD 37 (2002)). As for humans, there are reports of coughing, headache, pharyngeal irritation, tachypnea, tachycardia, rales, dyspnea, and reduced pulmonary function in cases of inhalation during the bleaching work of flowers (IRIS Tox Review (2000), ATSDR (2004)). As for experimental animals, there are reports of decreased activity, abdominal respiration, respiratory noise, labored breathing, dyspnea, the destruction of the alveolar walls, and pulmonary edema by inhalation exposure in rats (at doses equivalent to Category 1) (IRIS Tox. Review (2000), IRIS Summary (2000), ATSDR (2004), CICAD 37 (2002)) and decreased activity, hunched back posture, sedation, central nerve suppression, gasping, and respiratory symptoms (rales, reddish nasal discharge) by oral administration in rats (at doses equivalent to Category 1) (SIDS (2009)). Based on the above, this substance showed effects on the respiratory organs and narcotic effects, and it was classified in Category 1 (respiratory organs), and Category 3 (narcotic effects). |
| 9 | Specific target organ toxicity - Repeated exposure | Category 1 (respiratory organs) |
Danger |
H372 | P260 P264 P270 P314 P501 |
As for humans, effects on the respiratory organs (bronchitis, emphysema) were seen by occupational exposure (ACGIH (7th, 2001), CICAD 37 (2002), ATSDR (2004)). As for experimental animals, in a 2-month inhalation toxicity test with rats, effects on the lung (congestion, edema around the bronchioles) were found at 1 ppm, and in a 45-day inhalation toxicity test with rabbits, effects on the lung (alveolar hemorrhage and congestion) were observed at 2.5 ppm (CICAD 37 (2002), ATSDR (2004), IRIS Tox. Review (2000)). In a 90-day drinking water administration toxicity test with rats, goblet cell hyperplasia, squamous metaplasia, and inflammatory responses in the mucosa of the nasal cavity were observed at 2 mg/kg/day. These findings are considered to be due to hydrogen chloride gas in the drinking water (CICAD 37 (2002), ATSDR (2004), IRIS Tox. Review (2000)). As described above, effects on the respiratory organs were observed in humans, and effects on the respiratory organs were shown within the range for Category 1 also in animal experiments. Therefore, it was classified in Category 1 (respiratory organs). |
| 10 | Aspiration hazard | Not applicable |
- |
- | - | Gas (GHS definition) |
| Hazard class | Classification | Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Category 1 |
 Warning |
H400 | P273 P391 P501 |
From 96-hour LC50 = 0.02 mg/L for fish (Pimephales promelas) (ECETOC TR91, 2003), it was classified in Category 1. |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 1 |
Warning |
H410 | P273 P391 P501 |
If chronic toxicity data are used, then it is classified in Category 1 due to the unknown behavior of the inorganic compound in water, and 72-hour NOEC = 0.02 mg/L for algae (Pseudokirchneriella subcapitata) (SIDS, 2009). If acute toxicity data are used for a trophic level for which chronic toxicity data are not obtained, then it is classified in Category 1 due to the unknown behavior of the inorganic compound in water, and 96-hour LC50 = 0.02 mg/L for fish (Pimephales promelas) (ECETOC TR91, 2003). From the above results, it was classified in Category 1. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | No data available. |
NOTE:
| * A blank or "-" in a cell of classification denotes that the classification of the hazard class was not conducted. * Hazard_statement_and/or_Precautionary_statement will show when hovering the mouse over a code of Hazard_statement_and/or_Precautionary_statement. Hazard_statement_and/or_Precautionary_statement are also provided in the Excel file. * 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. * Codes assigned to each of the hazard statements and codes for each of the precautionary statement are based on the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) in United Nations. |