NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	87-86-5
Chemical Name	Pentachlorophenol
Substance ID	R02-B-027-MHLW, MOE
Classification year (FY)	FY2020
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 FY2014
Download of Excel format	Excel file

REFERENCE INFORMATION

Item	Information
Guidance used for the classification (External link)	GHS Classification Guidance for the Japanese Government (FY2019 revised edition (Ver. 2.0))
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 classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products. It was classified as "Not classified."
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
7	Flammable solids	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (HSDB (Access on April 2020)).
8	Self-reactive substances and mixtures	Not classified (Not applicable)	- -	-	-	There are no chemical groups present in the molecule associated with explosive or self-reactive properties. It was classified as "Not classified."
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
10	Pyrophoric solids	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (HSDB (Access on April 2020)).
11	Self-heating substances and mixtures	Not classified	- -	-	-	It was classified as "Not classified" from information that it is not combustible (HSDB (Access on April 2020)).
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified (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). It was classified as "Not classified."
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition). It was classified as "Not classified."
14	Oxidizing solids	Not classified (Not applicable)	- -	-	-	The substance is an organic compound containing chlorine and oxygen (but not fluorine) which are chemically bonded only to carbon or hydrogen. It was classified as "Not classified."
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. It was classified as "Not classified."
16	Corrosive to metals	Classification not possible	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	Not classified (Not applicable)	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified."

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] It was classified in Category 3 from (1) - (7). [Evidence Data] (1) LD50 for rats: 27-175 mg/kg (IARC 53 (1991)) (2) LD50 for rats: 80-120 mg/kg (ATSDR (2001)) (3) LD50 for rats: 80-175 mg/kg (NTP TR483 (1999)) (4) LD50 for rats: 150-200 mg/kg (ACGIH (7th, 2014)) (5) LD50 for rats: 150 mg/kg (EHC 71 (1987)) (6) LD50 for rats: males: 146 mg/kg, females: 175 mg/kg (EHC 71 (1987)) (7) LD50 for rats: males: 155 mg/kg, females: 137 mg/kg (EPA Pesticides RED (2008))
1	Acute toxicity (Dermal)	Category 2	Danger	H310	P302+P352 P361+P364 P262 P264 P270 P280 P310 P321 P405 P501	[Rationale for the Classification] It was classified in Category 2 from (1) - (5). New information sources were used because data (40 mg/kg) in Patty (4th, 1999), which was used in the previous classification, could not be identified in Patty (6th, 2012). Therefore, the classification result was changed from the previous classification. [Evidence Data] (1) LD50 for rats: 96-330 mg/kg (ACGIH (7th, 2014)) (2) LD50 for rats: 105 mg/kg (Environmental Risk Assessment for Chemical Substances vol. 1 (Ministry of the Environment, 2002)) (3) LD50 for rats: 149 mg/kg (MAK (DFG) vol.3 (1992)) (4) LD50 for rats: 320 mg/kg (EHC 71 (1987)) (5) LD50 for rats: 330 mg/kg (EHC 71 (1987))
1	Acute toxicity (Inhalation: Gases)	Not classified	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified."
1	Acute toxicity (Inhalation: Vapours)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 2	Warning	H315	P302+P352 P332+P313 P362+P364 P264 P280 P321	[Rationale for the Classification] It was classified in Category 2 from (1) - (4). [Evidence Data] (1) Exposure to this substance can irritate the skin and eye (ATSDR (2001), EHC 71 (1987), MAK (DFG) vol.3 (1992)). (2) Acute toxicity data indicated that this substance was a moderate to severe eye irritant and a mild skin irritant (ACGIH (7th, 2014)). (3) In a skin irritation test with rabbits according to EPA OPPTS 870.2500, moderate irritation was seen after 72 hours (EPA Pesticides RED (2008)). (4) Skin disease or disorder of the respiratory tract/lung due to work involving exposure to this substance was described in Article 35 of the Ordinance for Enforcement of the Labor Standards Act (Notice No. 33, 1996).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] It was classified in Category 2 from (1) - (4). [Evidence Data] (1)Exposure to this substance can irritate the skin and eye (ATSDR (2001), EHC 71 (1987), MAK (DFG) vol.3 (1992)). (2) Dust of this substance is irritating to the eye (ACGIH (7th, 2014)). (3) Acute toxicity data indicated that this substance was a moderate to severe eye irritant and a mild skin irritant (ACGIH (7th, 2014)). (4) In an eye irritation test with rabbits according to EPA OPPTS 870.2400, findings in the cornea were found at day 7 post-application (EPA Pesticides RED (2008)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1). The classification result was changed due to new data obtained. [Evidence Data] (1) It was reported to be negative in a skin sensitization test with guinea pigs (Buehler test) according to EPA OPPTS 870.2600 (EPA Pesticides RED (2008)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] From (1), (2), it was classified as "Not classified" based on expert judgment. [Evidence Data] (1) As for in vivo, it is reported that it was negative in micronucleus tests in rat bone marrow or mouse bone marrow, negative in a chromosomal aberration test in rat hepatocytes, positive in a sister chromatid exchange test in rat hepatocytes, and negative in a gene mutation test in the liver of transgenic mice (IARC 117 (2019), NTP RoC (14th, 2016), IRIS Tox Review (2010), Qualitative Carcinogenicity Assessment (Ministry of the Environment, 2003)). (2) As for in vitro, it is reported that there were negative results in most bacterial reverse mutation tests, but there were positive results in some cases (TA98 (S9+)). In test systems in cultured mammalian cells, it is reported that it was positive in a chromosomal aberration test and a sister chromatid exchange test, positive and negative in a chromosomal aberration test in human lymphocytes, and negative in a sister chromatid exchange test in human lymphocytes. It is reported that DNA damage tests in human mucous membrane cells or cultured mammalian cells gave positive and negative results (IARC 117 (2019), NTP RoC (14th, 2016), IRIS Tox Review (2010), Qualitative Carcinogenicity Assessment (Ministry of the Environment, 2003)). [Reference Data, etc.] (3) As for data in humans, although they were results based on a few workers, there is knowledge that it was positive and negative for chromosomal aberrations and negative for sister chromatid exchange in peripheral blood lymphocytes of workers exposed to this substance (IARC 117 (2019), NTP RoC (14th, 2016), IRIS Tox Review (2010), Qualitative Carcinogenicity Assessment (Ministry of the Environment, 2003)).
6	Carcinogenicity	Category 1A	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] It was classified in Category 1A on the basis that IARC classified it in Group 1 because there was sufficient evidence of carcinogenicity for both humans and experimental animals from (1) - (6). [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in Group 1 by IARC (IARC 117 (2019)), A3 by ACGIH (ACGIH (7th, 2014)), L (likely to be carcinogenic to humans) by EPA (IRIS (2010)), and NTP classified pentachlorophenol and by-products of its synthesis in R (Reasonably anticipated to be human carcinogens) (NTP RoC (14th, 2016)). And it was classified in 2 in MAK (DFG) (DFG List of MAK and BAT values (2019)) and 2 in EU CLP (EU CLP classification (Access on May 2020)). (2) As epidemiological studies on cancer risk related to exposure to this substance, four occupational cohort studies and seven case-control studies were reported, and increased risk of non-Hodgkin lymphoma (NHL) after exposure to this substance was reported in the four cohort studies and three case-control studies. In a cohort study in 27,000 male workers employed for at least one year in sawmills in Canada, there were significant positive correlations in the incidence of NHL and multiple myeloma and cumulative exposure to this substance. In a small cohort study in workers who had been engaged in the production of this substance and had been employed between 1937 and 1980 by a chemical company in the USA, significantly elevated mortality from NHL due to exposure to this substance was observed (IARC 117 (2019)). (3) In a carcinogenicity test by 2-year diet administration of this substance (purity 90.4%) to male and female mice, there were significant increases in the incidences of hepatocellular neoplasms (adenoma and carcinoma) and adrenal pheochromocytoma in males and hemangiosarcoma in females. From this, it was concluded that there was clear evidence of the carcinogenicity of this substance in male mice, and there was some evidence of carcinogenicity in female mice (NTP TR349 (1989), IARC 117 (2019)). (4) In a carcinogenicity test by 2-year diet administration of this substance (purity 99%) to male and female rats, increased incidences of malignant mesothelioma and nasal squamous cell carcinoma were observed in males. No formation of neoplasms was seen in females. From this, there was no evidence of the carcinogenicity of this substance in female rats, and there was some evidence of carcinogenicity in male rats (NTP TR483 (1999), IARC 117 (2019)). (5) In a test by 20-week or 26-week dermal application of this substance to female transgenic mice, an increase in the incidence of skin papilloma was observed. Three initiation-promotion studies (in the diet) in mice were conducted, and the formation of hepatocellular adenoma or carcinoma, and cholangioma and cholangiocarcinoma in the liver were induced (IARC 117 (2019)). (6) As mechanisms of carcinogenesis of this substance, there is strong evidence that this substance (1) induces oxidative stress, (2) is genotoxic, (3) modulates receptor-mediated effects, (4) alters cell proliferation, (5) alters cell death or nutrient supply, and all of these can operate in humans (IARC 117 (2019)).
7	Reproductive toxicity	Category 1B	Danger	H360	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1B. [Evidence Data] (1) The Japan Society for Occupational Health (JSOH) classified this substance in Group 2 of reproductive toxicant (substance which was determined to have a possiblity to show reproductive toxicity to humans) on the basis that fetal toxicity was observed at a dose at which no maternal toxicity was observed in test animals, and that a decrease in thyroid hormone secretion which had an important role in growth and development was observed in multiple species (OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2014)). (2) In a developmental toxicity study with female rats orally dosed on days 6 to 15 of gestation, delayed ossification of the skull bones, subcutaneous edema, and abnormalities of the rib, vertebra, and sternum were observed at a dose at which no maternal toxicity was observed (OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2014)). [Reference Data, etc.] (3) In a two-generation reproduction toxicity test with rats orally dosed, a decrease in offspring weight, an increased number of deaths of offspring before postnatal day 4, delayed sexual maturation of offspring, a decrease in sperm count, a reduced number of implantations, increased resorption of fetuses, etc. were observed at a dose at which systemic toxicity appeared in dams (OEL Documentations (Reproductive toxicant classification) (Japan Society for Occupational Health (JSOH), 2014)).
8	Specific target organ toxicity - Single exposure	Category 1 (nervous system, heart), Category 3 (respiratory tract irritation)	Danger Warning	H370 H335	P308+P311 P260 P264 P270 P321 P405 P501 P304+P340 P403+P233 P261 P271 P312	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1 (nervous system, heart) and Category 3 (respiratory tract irritation). [Evidence Data] (1) This substance was known to uncouple oxidative phosphorylation, and in an acute and chronic inhalation or dermal exposure, multiple cases of a rise in body temperature, increases in respiration and heart rate, neurogenic muscular weakness, convulsions, and death due to cardiac failure via its action mechanism were reported (ACGIH (7th, 2014)). (2) Common symptoms of poisoning of this substance were ataxia, mental and physical fatigue, headaches, dizziness, disorientation, anorexia, nausea, vomiting, dyspnea, hyperpyrexia, tachycardia, and a rise in metabolic rate. Most prominent symptoms were extreme weakness, elevated body temperature, and profuse sweating. Death was due to cardiac arrect, and poisoning victims usually showed a marked rigor mortis (EHC 71 (1987)). (3) Symptoms of acute systemic poisoning were headache, profuse sweating, depression, nausea, weakness, and sometimes fever, and frequent symptoms were tachycardia, tachypnea, pain in the chest, thirst, and abdominal colic (IPCS PIM 405 (1989)). (4) The threshold limit value in the work environments by the ACGIH was set based on the reports of upper respiratory tract irritation and eye irritation due to occupational exposure to this substance (ACGIH (7th, 2014)). [Reference Data, etc.] (5) It was reported that, in dogs, rabbits, rats, and guinea pigs, quickening of respiration, an increase in blood pressure, fever, hyperglycemia, urinal sugar, and promotion of peristalsis were observed after absorption of this substance in large amounts (the dose level and route were unknown) (OEL Documentations (Japan Society for Occupational Health (JSOH), 1989)). (6) It was reported that, in rodents, hyperthermia, tremors, spasms, and loss of righting reflex associated with uncoupling of oxidative phosphorylation were observed as acute toxic symptoms of poisoning of this substance (NTP TR483 (1999)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (nervous system, respiratory organs, heart, liver, kidney, skin)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (5) and (9), there was information that effects on the nervous system, respiratory organs, heart, liver, kidney, skin were observed in humans. Based on (7) and (8), there was information that effects on the kidney at a dose within the range for Category 1, and effects on the liver at a dose within the range for Category 2 were observed in experimental animals. Therefore, it was classified in Category 1 (nervous system, respiratory organs, heart, liver, kidney, skin). There was a possibility that effects on the skin were due to impurities contained in commercial products as indicated in (6). As a result of review of the information, it was determined that the blood system which was considered to be a target organ in the previous classification was not included in the target organ of this substance, and the classification results were changed from the previous classification. [Evidence Data] (1) It was reported that, among workers employed in pressure-treating wood with this substance, insomnia and vertigo were observed (EHC 71 (1987)). It was also reported that an increase in subjective symptoms such as fatigue, distractibility, attenuated motivation, and depressed mood, and impaired performance on several objective tests of neurobehavioral performance were observed in 15 women with elevated blood levels of this substance and gamma-hexachloro-cyclohexane (CAS RN 58-89-9) due to exposure to wood preserving chemicals (ATSDR (2001)). (2) It was reported that workers exposed to airborne concentrations of 1 mg/m3 or more of this substance complained of painful nasal irritation (EHC 71 (1987), MAK(DFG) vol.3 (1992)). (3) Human hepatic and renal abnormalities associated with occupational exposure to or the misuse of this substance were known, and hepatic abnormalities such as fatty infiltration, centrilobular degeneration, and increased in AST and ALT activities were reported (NTP TR483 (1999)). As for the kidney, reversible functional changes of the kidney with reductions in creatinine clearance and resorption of phosphorus were reported (EHC 71 (1987)). (4) This substance was known to uncouple oxidative phosphorylation, and in an acute and chronic inhalation or dermal exposure, multiple cases of a rise in body temperature, increases in respiration and heart rate, neurogenic muscular weakness, convulsions, and death due to cardiac failure via its action mechanism were reported (ACGIH (7th, 2014)). (5) It was reported that this substance caused irritation to the skin, nasal mucosa, and respiratory tract, chloracne, depressed feeling, headache, porphyria cutanea tarda, functional changes of the liver and kidney, insomnia, and vertigo in humans (EHC 71 (1987)). (6) It was reported that workers with direct skin contact to this substance developed chloracne, and it was considered that this was due to dioxin-related impurities present in commercial products of this substance (ACGIH (7th, 2014)). (7) In a 6-month test by dosing this substance to mice by feeding, at or above 200 ppm (converted guidance value: 34.3 to 34.6 mg/L, within the range for Category 2), brown pigmentation of the urinary bladder surface epithelium, metaplasia of the nasal mucosa, an increase in absolute liver weight, and hepatocellular karyomegaly, cytomegaly, and degeneration were observed. In females, at or above 200 ppm (converted guidance value: 34.6 mg/L, within the range for Category 2), an increase in locomotor activity, and an increase in startle response were observed (NTP TR349 (1989)). (8) In a 2-year test by dosing this substance to rats by feeding, brown pigmentation of the renal tubules in males at or above 10 mg/kg (within the range for Category 1), and an increase in serum ALT activities in males and females at 30 mg/kg (within the range for Category 2) were observed (EHC 71 (1987), MAK (DFG) vol.3 (1992)). (9) As for this substance, Article 35 of the Ordinance for Enforcement of the Labor Standards Act described skin disorders, disorders in the anterior part of the eye, respiratory tract and lung disorders, or hypermetabolism (Ministry of Labour Notification No. 33 (1996)). [Reference Data, etc.] (10) Commercial products of this substance contained polychlorinated dibenzo-p-dioxins, dibenzofurans (CAS RN 132-64-9), etc. as impurities, and toxicity due to these impurities were also suggested (NTP TR483 (1999)). (11) It was reported that a 21-year-old man who had been continuously exposed to 3% of this substance and 1.5% of tetrachlorophenol (CAS RN 58-90-2) died due to aplastic anemia, but only one case was reported (OEL Documentations (Japan Society for Occupational Health (JSOH), 1989)). A study of the relationship between unexplained anemia and exposure to this substance in 128 Canadian woodworkers concluded that exposure to this substance was not related to the prevalence of anemia in woodworkers (EHC 71 (1987)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] 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 Short term (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour LC50 = 0.013 mg/L for fish (Oryzias latipes) (Environmental Risk Assessment for Chemical Substances Vol. 5 (Ministry of the Environment, 2006)).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 because it was not rapidly degradable (a 28-day degradation rate by BOD: 1% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1982)) and due to NOEC = 0.013 mg/L for fish (Oryzias latipes) (Results of Aquatic Toxicity Tests of Chemicals conducted by Ministry of the Environment in Japan (Ministry of the Environment, 2001)).
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.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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