GHS Classification Result
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 98-54-4 |
| Chemical Name | 4-tert-Butylphenol |
| Substance ID | H27-B-13-METI/M-022B_P |
| Classification year (FY) | FY2015 |
| 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 | FY2008 |
| 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 |
- |
- | - | 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 |
- |
- | - | It is combustible, but the classification is not possible due to no data. |
| 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 | Not classified |
- |
- | - | It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 510 deg C (EU-RAR (2008)). |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to solid (melting point <= 140 deg C) 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 |
- |
- | - | Solid (GHS definition). |
| 14 | Oxidizing solids | Not applicable |
- |
- | - | The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. |
| 15 | Organic peroxides | Not applicable |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | Test methods applicable to solid 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 classified |
- |
- | - | There are 10 reports of LD50 values for rats within the ranges of 801-5,660 mg/kg and > 2,000 mg/kg. Three reports correspond to Category 4 and 7 reports correspond to "Not classified" (4 of them correspond to "Not classified" (Category 5 in the UN GHS classification): 2,990 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008), DFGOT Vol. 11 (1998)), 3,500 mg/kg, 4,000 mg/kg (EU-RAR (2008)), and 3,620 mg/kg (females) (EU-RAR (2008), Hazard Assessment Report (CERI, NITE, 2007))). Therefore, this substance was classified as "Not classified" (Category 5 in the UN GHS classification) to which the greatest number of reports (4) corresponded. |
| 1 | Acute toxicity (Dermal) | Not classified |
- |
- | - | There are five reports of LD50 values for rabbits: 1,580 mg/kg (PATTY (6th, 2012)), > 2,000 mg/kg (EU-RAR (2008)), 2,318 mg/kg (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008), DFGOT Vol. 11 (1998)), > 5,000 mg/kg (DFGOT Vol. 11 (1998)), and > 16,000 mg/kg (Hazard Assessment Report (CERI, NITE, 2007)). One report corresponds to Category 4 and four reports correspond to "Not classified" (one of them corresponds to "Not classified" (Category 5 in the UN GHS classification)). Therefore, this substance was classified as "Not classified" to which the greatest number of reports (three) corresponded. |
| 1 | Acute toxicity (Inhalation: Gases) | Not applicable |
- |
- | - | Solid (GHS definition) |
| 1 | Acute toxicity (Inhalation: Vapours) | Not applicable |
- |
- | - | Solid (GHS definition). Besides, it is reported that when rats were exposed by inhalation to the saturated vapor of this substance for six hours (a converted 4-hour equivalent value: 6.0 ppm) (EU-RAR (2008), DFGOT Vol. 11 (1998)) or for eight hours (a converted 4-hour equivalent value: 6.9 ppm) (EU-RAR (2008)), there were no deaths in either case. |
| 1 | Acute toxicity (Inhalation: Dusts and mists) | Not classified |
- |
- | - | On the basis of a reported LCLo value for rats (4 hours) of 5.6 mg/L (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), PATTY (6th, 2012), EU-RAR (2008), Hazard Assessment Report (CERI, NITE, 2007), DFGOT Vol. 11 (1998)), this substance was classified as "Not classified." Besides, as the test substance is a solid, the reference value for dusts was applied. |
| 2 | Skin corrosion/irritation | Category 2 |
 Warning |
H315 | P302+P352 P332+P313 P362+P364 P264 P280 P321 |
It is reported that, in a skin irritation test with rabbits (OECD TG 404), severe irritation responses were observed as a result of a 4-hour semi-occlusive application of 500 mg of this substance, and these were resolved within 14 days (EU-RAR (2008)). It is reported that in separate skin irritation tests with rabbits (OECD TG 404), it was irritating (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)), severely irritating (EU-RAR (2008)), and corrosive (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007)). In addition, there is a report that, in a skin irritation study with rabbits (US DOT regulation 173.1300), severe irritation or corrosion was observed following a 4-hour semi-occlusive application of 500 mg of this substance (EU-RAR (2008)). There are also descriptions that necrosis, scabbing, and desquamation of the skin were observed following a 4-hour or 24-hour application of 500 mg of this substance but this was resolved by 17 days after administration (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008), DFGOT Vol. 11 (1998)). In the EU-RAR (2008), it is regarded that this substance is severely irritating to the skin. From the above, this substance was classified in Category 2. |
| 3 | Serious eye damage/eye irritation | Category 1 |
 Danger |
H318 | P305+P351+P338 P280 P310 |
It is reported that, in an eye irritation test with rabbits, severe corneal injury, iritis, and severe conjunctival irritation responses were observed following application of 10 mg or 80 mg of this substance. It is reported it was severely irritating, and reversibility was not seen in the case of 80 mg (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008)). From the above, this substance was classified in Category 1. |
| 4 | Respiratory sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, as for occupational exposure, while there is a report that a bronchial provocation test with this substance elicited a dual asthmatic reaction (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)), this report was judged to be insufficient for use in this classification as it involves only one case. |
| 4 | Skin sensitization | Classification not possible |
- |
- | - | Classification not possible due to lack of data. Besides, there are reports that this substance was negative in a maximization test with guinea pigs (OECD TG 406) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008)). On the other hand, there are a few reports of positive reactions in patch tests in humans (Initial Risk Assessment Report (NITE, CERI, NEDO, 2007), EU-RAR (2008)). It is concluded in EU-RAR (2008) that this information on animal tests and humans are insufficient to draw a conclusion on this substance as a sensitizer (EU-RAR (2008)). Accordingly, this substance was classified as "Classification not possible." |
| 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, this substance was negative in a micronucleus test in mouse bone marrow cells (Hazard Assessment Report (CERI, NITE, 2007), JECDB (Access on November 2015), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). As for in vitro, this substance was negative in bacterial reverse mutation tests and in a mouse lymphoma test with mammalian cultured cells, and positive and negative results were seen in chromosomal aberration tests with mammalian cultured cells (Hazard Assessment Report (CERI, NITE, 2007), JECDB (Access on November 2015), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). |
| 6 | Carcinogenicity | Classification not possible |
- |
- | - | In a two-stage carcinogenicity study in which male rats were dosed with this substance in the diet at 15,000 ppm (equivalent to 1,070 mg/kg/day) for 51 weeks after being dosed with nitrosoguanidine (MNNG) as an initiator for one week, the treatment group that received MNNG pretreatment showed an increased incidence of papillomas or squamous cell carcinomas in the forestomach in comparison to the MNNG-pretreated control group, suggesting a promoter activity of this substance. However, it is described that the treatment group that only received this substance without MNNG pretreatment showed only hyperplasia in the forestomach and no increased incidence of tumors, and this substance has no initiating activity (SIDS (2012), Hazard Assessment Report (CERI, NITE, 2007)). There is no other information on the carcinogenicity of this substance. Therefore, classification was not possible due to lack of data. |
| 7 | Reproductive toxicity | Category 2 |
 Warning |
H361 | P308+P313 P201 P202 P280 P405 P501 |
There is no information on the reproductive effects of this substance in humans. In experimental animals, in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by the oral route (OECD TG 422), no adverse effects on the fertility of the parents or on the survival rate or body weight changes in the pups through postnatal day 4 were seen at doses of up to 200 mg/kg/day (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), Hazard Assessment Report (CERI, NITE, 2007), PATTY (6th, 2012)). However, in a two-generation reproduction toxicity study with rats dosed by the oral route (by feeding), in the F0 parental animals, reduced body weight gain and reduced food consumption in both sexes and reduced ovary weights and atrophy of the vaginal epithelium in females were seen at 2,500 ppm (equivalent to 200 mg/kg/day) or higher. At 7,500 ppm (equivalent to 600 mg/kg/day), a decrease in the incidence of growing follicles, an increase in the incidence of primordial follicles, and changes in the estrous cycle (greater and lower incidences of females that were in proestrus and metoestrus, respectively) were observed, and a slight decrease in the number of implantation sites, and lower litter weight were also observed (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)). In the F1 pups, reduced body weights were observed at 2,500 ppm or higher, and a slight decrease in litter size and a decrease in postnatal survival rate were seen at 7,500 ppm. Also in the F1 parental animals, reduced body weight gain (in males) and reduced food consumption (in females) were seen, and at 7,500 ppm, reduced body weight gain (in females), decreased ovarian and uterine weights, atrophy of the vaginal epithelium, and a change in the ratio of growing follicles to primordial follicles were observed similar to the F0 females. In the F2 pups, reduced body weights at 2,500 ppm or higher, and smaller litter size at 7,500 ppm were observed (EU-RAR (2008), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)). As described above, no reproductive effects were detected in the combined repeated dose toxicity study with the reproduction/developmental toxicity screening test in rats. However, in the two-generation reproduction toxicity test with rats, at the doses where reduced body weight gain were seen in the parental animals of both the F0 and F1 generations, histological changes in the genetic organs and changes in the estrous cycle were observed in females, and smaller litter sizes and a decreased survival rate (in F1 pups only) in addition to reduced body weights. Therefore, this substance was classified in Category 2 for this hazard class. Besides, the EU classified this substance in Repr. 2 (ECHA CL Inventory (Access on November 2015)). The classification was changed based on the data from the information sources listed in List 1 such as the EU-RAR (2008) which was released after the previous classification. |
| 8 | Specific target organ toxicity - Single exposure | Category 3 (Respiratory tract irritation) |
Warning |
H335 | P304+P340 P403+P233 P261 P271 P312 P405 P501 |
This substance is severely irritating to the human respiratory tract, and cough and throat pain through inhalational exposure and nausea and vomiting through ingestion were seen (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015)). In experimental animals, sluggishness, unsteady gait, and prostration are reported in oral administration of rats (LD50 = 3620-5360 mg/kg, exceeding Category 2); perinasal, perioral, and periocular mucosal irritation and respiratory distress are reported in inhalation exposure in rats (5.6 mg/L, exceeding Category 2) (Hazard Assessment Report (CERI, NITE, 2007), EU-RAR (2008), SIDS (2012), PATTY (6th, 2012)). From the above, this substance is irritating to the respiratory tract and was classified in Category 3 (respiratory tract irritation). |
| 9 | Specific target organ toxicity - Repeated exposure | Classification not possible |
- |
- | - | In humans, in addition to depigmentation of the skin, cases involving liver damage (impairment of liver functions, hepatomegaly, hepatocellular fatty degeneration and fibrosis etc.) or hypertrophy of the thyroid gland were reported in workers occupationally exposed to this substance in chemical plants in the UK and Australia in the 1970s (DFGOT Vol. 11 (1998)). However, workers exposed to this substance in chemical plants in Germany only showed depigmentation of the skin without any effects on the liver or thyroid gland. It is concluded in the EU risk assessment that, in humans, the effect of exposure to this substance is only depigmentation of the skin and there is no available data with regard to systemic toxicity effects (EU-RAR (2008)). Besides, it cannot be explained how the irritation/sensitization properties of this substance are involved in the depigmentation of the skin. Because electron microscopic investigations of biopsies of depigmented skin areas revealed a lack of melanocytes, defective melanocytes, etc., mechanisms such as a reduction in the production of melanin are being considered (EU-RAR (2008)). However, it is described that this effect of depigmentation of the skin is reversible by avoiding exposure to this substance and removing it from the skin (EU-RAR (2008)). In experimental animals, in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test with rats dosed by the oral route (gavage), other than a noisy respiratory sound, which was considered to be caused by irritation, decreases in plasma albumin and total protein were observed at the high dose of 200 mg/kg/day (converted guidance value: 93 mg/kg/day), and there were no findings based on which a target organ can be specified (Hazard Assessment Report (CERI, NITE, 2007), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). In addition, in a two-generation reproduction toxicity study with rats dosed by the oral route (by feeding), at doses equivalent to 200-600 mg/kg/day which exceed the range of Category 2, reduced body weight gain, increased liver weights, atrophy of the vaginal epithelium, etc. were observed in the parental animals (Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). In addition, in two-stage carcinogenicity studies in which male rats or male hamsters were dosed with this substance in the diet, hyperplasia in the forestomach were seen in the group dosed only with this substance in both rats and hamsters, but the converted dose exceeded 1,000 mg/kg/day (Hazard Assessment Report (CERI, NITE, 2007), Environmental Risk Assessment for Chemical Substances Vol.13 (Ministry of the Environment, 2015), EU-RAR (2008)). As stated above, as for humans, it was assessed in DFGOT that according to the earlier study report, anomalies in the liver and thyroid gland were found in addition to depigmentation of the skin by occupational exposure (DFGOT Vol. 11 (1998)). However, it is concluded in the EU assessment that the skin is the only target organ in humans occupationally exposed to this substance (EU-RAR (2008)). Based on the findings in the experimental animals discussed above, there were no unequivocal changes by which the liver or thyroid gland can be identified to be a target organ of this substance. No target organ can be identified on the basis of other existing findings in experimental animals either. Therefore, since this substance is considered to be equivalent to "Not classified" for the oral route, but there is no information on toxicity by other exposure routes in experimental animals, this substance was classified as "Classification not possible" due to lack of data for this hazard class. Besides, the skin was not adopted as a target organ because the adverse effects on the skin of this substance were covered in the skin irritation/corrosion hazard class, and the vitiligo due to depigmentation was regarded to be a reversible change and judged to be of low severity. Also, the liver and thyroid gland, which were adopted as the target organs in the previous classification, were excluded for the reasons stated above. |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | Classification not possible due to lack of data. |
| 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 96-hour LC50/EC50 = 1.9 mg/L for crustacea (Crangon septemspinosa) (EU-RAR, 2008), it was classified in Category 2. |
| 11 | Hazardous to the aquatic environment (Long-term) | Category 2 |
 - |
H411 | P273 P391 P501 |
Due to being not rapidly degradable (a degradation rate by 14-day BOD in an inherent test = 0%, a degradation rate by TOC = 1.2% (Official Bulletin of Ministry of International Trade and Industry, 1977)), and 72-hour NOEC (r) = 0.32 mg/L for algae (Pseudokirchneriella subcapitata) (EU-RAR, 2008, Environmental Risk Assessment for Chemical Substances vol. 13 (Ministry of the Environment, 2015)), it was classified in Category 2. |
| 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. |