GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 115-96-8 |
| Chemical Name | Tris(2-chloroethyl) phosphate |
| Substance ID | H28-B-08-METI, M-010B |
| Classification year (FY) | FY2016 |
| Ministry who conducted the classification | Ministry of Economy, Trade and Industry (METI)/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 (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 |
- |
- | - | 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 |
- |
- | - | Based on a flash point of 202 deg C (closed cup) (ICSC (2007)), it was classified as "Not classified." |
| 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 480 deg C (ICSC (2007)). |
| 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 classified |
- |
- | - | There is a metalloid (P) present in the molecule, but due to the water solubility data of 7,820 mg/L (20 deg C, EU-RAR (2009)), it is estimated that it does not react vigorously with water. |
| 13 | Oxidizing liquids | Classification not possible |
- |
- | - | The substance is an organic compound containing oxygen which is chemically bonded to the element other than carbon or hydrogen (P), but the classification is not possible due to no data. |
| 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. |
| 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
P264 P270 P330 P501 |
Based on the LD50 values (OECD TG 401) of 1,182 mg/kg (male) and 1,123 mg/kg (female) for rats (EU-RAR (2009)), this substance was classified in Category 4. Additionally, the Chemical Substance Hazard Data (CERI, 1999) used in the previous classification was not adopted for the classification since it is an information source in List 3. |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | Based on the report that the LD50 value for rabbits is > 2,150 mg/kg (EU-RAR (2009), SIAP (2006)), this substance was classified as "Not classified." Additionally, the Chemical Substance Hazard Data (CERI, 1999) used in the previous classification was not adopted for the classification since it is an information source in List 3. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Liquid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Not classified |
- |
- | - | Based on the LC50 value (4 hours) of > 5,000 mg/m3 (> 5.0 mg/L) (ATSDR (2012)) for rats, this substance was classified as "Not classified." The category was revised based on the new data. Besides, this LC50 value is higher than the saturated vapor pressure concentration (81.19 ppm (0.95 mg/L)), so the reference value as mist was applied. |
| 2 | Skin corrosion/irritation | Not classified |
- |
- | - |
In two reports on skin irritation tests (OECD TG 404) using rabbits, it is reported that slight erythema was observed, but this resolved within 24 hours (EU-RAR (2009)). In addition, it is described that in a skin irritation test using rabbits, as the result of applying 0.5 mL of this substance for 4 hours under a semi-occlusive dressing, slight erythema was observed in all animals on Day 1 after application, but there were no signs of irritation (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EHC 209 (1998)). From the above, this substance was classified as "Not classified" (Category 3 in UN GHS classification). Based on the added information, the category was changed according to the GHS Classification Guidance for the Japanese Government. |
| 3 | Serious eye damage/eye irritation | Category 2B |
Warning |
H320 |
P305+P351+P338
P337+P313 P264 |
In two reports on skin irritation tests (only one of them is according to OECD TG 405) using rabbits, it is reported that mild conjunctival edema and redness were observed, and that they resolved within 3 days (EU-RAR (2009)). In addition, it is described that as a result of applying 0.1 mL of this substance to rabbit eyes, slight conjunctival redness was observed in each animal on Day 1 after application and continued till Day 2 in one animal of them (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EHC 209 (1998)). From the above, this substance 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 |
- |
- | - | There is information that in a Buehler test using guinea pigs, this substance did not show sensitization (EU-RAR (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)), but it was judged as inadequate data to use for the classification since details of the test conditions etc. are unknown. Additionally, in SIAP (2006), it was concluded that this substance is not a sensitizer to the skin based on the read-across approach using the skin sensitization studies results on Tris(2-chloro-1-methylethyl) phosphate (TCPP) and Tris[2-chloro-1-(chloromethyl)ethyl] phosphate (TDCP) (SIAP (2006)). |
| 5 | Germ cell mutagenicity | Classification not possible |
- |
- | - | As for in vivo, it is reported that there is an inadequate report on a dominant lethal test in rats. A micronucleus test using Chinese hamster bone marrow cells shows an ambiguous result, and micronucleus tests using rats and mice bone marrow cells are negative (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ATSDR (2012), EU-RAR (2009)). As for in vitro, a bacterial reverse mutation test is negative, a mouse lymphoma assay and a gene mutation test using mammalian cultured cells are negative, a chromosomal aberration test using mammalian cultured cells is negative, and sister chromatid exchange tests using mammalian cultured cells are positive and negative (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ATSDR (2012), EU-RAR (2009), NTP DB (Access on October 2016)). From the above, this substance was classified as "Classification not possible" according to the GHS Classification Guidance for the Japanese Government. |
| 6 | Carcinogenicity | Category 2 |
 Warning |
H351 |
P308+P313
P201 P202 P280 P405 P501 |
In 2-year carcinogenicity studies using rats and mice administered by gavage, in rats of both sexes, an increase in the incidence of renal tubule adenomas was observed, along with a slightly increased incidence of thyroid gland follicular cell neoplasms (NTP TR391 (1991)). Moreover, in mice, marginally increased incidences of renal tubule adenomas in males and a marginally increased incidence of adenomas of the Harderian gland in females were observed. NTP concluded that evidence of carcinogenicity is clear for male and female rats and is equivocal for male and female mice (NTP TR391 (1991)). On the other hand, in a 18-month carcinogenicity study using mice administered by feeding, increased incidences of renal tubule adenomas in both sexes and renal tubule carcinomas in males as well as increased incidences of hepatocellular adenomas/carcinomas in males, and squamous cell papilloma/carcinomas in the forestomach and leukemia in females were observed (EU-RAR (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). As for the classifications by other organizations, IARC classified this substance in Group 3 based on the limited evidence in experimental animals (IARC 71 (1999)), whereas the EU classified this substance as Carc. 2 (ECHA C&L Inventory (Access on October 2016)). From the above, since evidence of carcinogenicity was obtained in two species of experimental animals, the EU classification result was adopted and the substance was classified in Category 2 for this hazard class. |
| 7 | Reproductive toxicity | Category 1B |
Danger |
H360 |
P308+P313
P201 P202 P280 P405 P501 |
In a continuous breeding study using mice (18-week administration by gavage, during which mating and pregnancy were conducted 5 times), decrease in the number of pregnant females was observed in the fifth round of mating at the mid dose (350 mg/kg/day) and in the third round of mating at the high dose (700 mg/kg/day). Pregnant females were not observed in the fourth and subsequent mating in the high dose group. In addition, a decrease in the number of litters was observed above the mid dose. Moreover, as a result of crossover mating of males and females in the high dose group and males and females in the control group, pregnancy and fertility rates were significantly decreased in the group in which males of the high dose group were mated with the females of the control group, as compared with the group in which the males of the control group were mated with the females of the dosed group. In the males in the high dose group, a decrease in epididymal sperm count, lower epididymal sperm motility and an increase in the percentage of abnormal sperm were observed (EU-RAR (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ATSDR (2012)). In addition, in a study in which male rats were mated with untreated females after inhalation exposure for 4 months, a decrease in sperm count, a lower sperm motility, an increase in morphologically abnormal sperm number, etc. are observed at 0.5 mg/m3 or above; in addition, an increase in embryo resorptions, a decrease in the number of fetuses per litter, and a decrease in pregnancy rate are observed at 1.5 mg/m3 (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). On the other hand, in a study using pregnant female rats dosed by gavage administration during the organogenesis period, deaths (7/30 animals), decreased food consumption, and symptoms (piloerection, general weakness, and so on) were observed at the high dose (200 mg/kg/day) of dams, and skeletal variations (variations in cervical ribs, lumbar ribs, and sternebrae) were found at the mid-dose (100 mg/kg/day) or higher in the fetuses. However, there were no deaths or increased malformations of embryos/fetuses related to administration of this substance, and no abnormalities were observed on the examination in postnatal growth, morphology and function in offspring. It is reported that the authors concluded that this substance does not show teratogenicity in rats even at the maternally toxic doses (EU-RAR (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), ATSDR (2012)). As for classifications by other organizations, the EU classified this substance as Repr. 1B (ECHA C&L Inventory (Access on October 2012)). From the above, both in the continuous breeding study using mice and the study using male rats exposed by inhalation, effects on sperm and a decrease in fertility were observed. Based on this and the EU's classification, this substance was classified in Category 1B. |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (central nervous system) |
Danger |
H370 |
P308+P311
P260 P264 P270 P321 P405 P501 |
There is no information on the single exposure to this substance in humans. As for experimental animals, it is reported that in a single oral dose study using rats, piloerection and salivation were observed at 800 mg/kg which is within the range of Category 2, or above, hunched posture, abnormal gait, lethargy, labored breathing, ptosis and pallor of the extremities were observed at 1000 mg/kg or above; and LD50 value was 1,150 mg/kg (EU-RAR (2009), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), EHC 209 (1998)). In addition, in rats, in a single oral dose of 350 mg/kg which is within the range of Category 2, or above, a dose-dependent increase in the frequency of rearing and tremor was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Moreover, there is a report that rats administered by a single oral dose at 275 mg/kg, equivalent to Category 1, convulsed within 60-90 min, and an extensive loss of CA1 hippocampal pyramidal cells was observed 7 days after administration (ATSDR (2012), EHC 209 (1998)). From the above, this substance was classified in Category 1 (central nervous system). It was classified in Category 3 (narcotic effects) in the previous classification. However, it is considered an irreversible effect since lethargy was observed only at doses close to lethal doses and disappearance of hippocampal pyramidal cells was also observed. Therefore, the classification result was changed. |
| 9 | Specific target organ toxicity - Repeated exposure | Category 2 (central nervous system, kidney) |
Warning |
H373 |
P260
P314 P501 |
In a 103-week repeated dose toxicity study using rats administered by gavage, at 88 mg/kg/day, which is equivalent to Category 2, an increased incidence of hyperplasia in the tubular epithelium (convoluted tubules in the renal cortex); focal lesions (reactive gliosis, hemorrhage, mineralization, pigment deposit or hemosiderin deposit) in the cerebral cortex and brain stem (gray matter, white matter); and lesions in the thalamus, hypothalamus, etc. (degeneration accompanied by bleeding, necrosis, and loss of neurons and neuropil etc. at sites where injuries had progressed) have been reported (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). Therefore, this substance was classified in Category 2 (central nervous system, kidney). Additionally, in the previous classification, it is described that in humans, "Clinical signs included weakness in arms and abdominal muscles and abnormalities in the electromyogram and nerve conduction velocities." However, it was one case, and since the citation in NICNAS (2001) was a personal communication (Personal communication to NICNAS (2000)), this was not adopted as evidence for classification. |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Additionally, from the numerical data (viscosity: 45 mPa*s (20 degC), density: 1.39 g/cm3 (25 degC)) listed in HSDB (Access on October 2016), the kinematic viscosity is calculated to be 32.4 mm2/sec (20/25 degC). |
| Hazard class | Classification |
Pictogram Signal word |
Hazard statement (code) |
Precautionary statement (code) |
Rationale for the classification | |
|---|---|---|---|---|---|---|
| 11 | Hazardous to the aquatic environment (Acute) | Category 2 |
- |
H401 |
P273
P501 |
From 48-hour ErC50 = 5.0 mg/L for algae (Desmodesmus subspicatus) (EU-RAR, 2009), it was classified in Category 2. |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 2 |
 - |
H411 |
P273
P391 P501 |
If chronic toxicity data are used, then it is classified in Category 2 because it is not rapidly degradable (Non-biodegradable, a degradation rate by BOD: 4 % (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1983)), and its 48-hour ErC10 = 0.65 mg/L for algae (Desmodesmus subspicatus) (EU-RAR, 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 3 because it is not rapidly degradable (Non-biodegradable, a degradation rate by BOD: 4 % (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, 1983)), and its 96-hour LC50 = 90 mg/L for fish (Carassius auratus) (Initial Risk Assessment (NITE, CERI, NEDO, 2008); EU-RAR, 2009; NICNAS, 2001; SIAP (Conclusions Agreed in SIAM 23), 2006). It was classified in Category 2 by drawing a comparison between the above results. |
| 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. |