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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	1314-62-1
Chemical Name	Divanadium pentaoxide
Substance ID	R03-B-012-MHLW
Classification year (FY)	FY2021
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)
New/Revised	Revised
Classification result in other fiscal year	FY2014 FY2007 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 (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.
2	Flammable gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
3	Aerosols	Not classified (Not applicable)	- -	-	-	Not aerosol products.
4	Oxidizing gases	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
5	Gases under pressure	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
6	Flammable liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
7	Flammable solids	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed Oct. 2021)).
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.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed Oct. 2021)).
11	Self-heating substances and mixtures	Not classified	- -	-	-	It is not combustible (GESTIS (Accessed Oct. 2021)).
12	Substances and mixtures which, in contact with water, emit flammable gases	Not classified	- -	-	-	It is estimated that it does not react vigorously with water from the measurement result on water solubility: 0.8 g/100 mL (ICSC (2018)).
13	Oxidizing liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	Classification not possible	- -	-	-	It is an inorganic compound containing oxygen, but the classification is not possible due to no data.
15	Organic peroxides	Not classified (Not applicable)	- -	-	-	It is an inorganic compound.
16	Corrosive to metals	Classification not possible	- -	-	-	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.

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] Based on (1) to (7), it was classified in Category 3 by adopting the category with the higher hazard. Besides, the category for this substance may differ depending on the form. Based on the new findings, the classification result was changed. [Evidence Data] (1) LD50 (analytical grade pulverized) for rats (males): 474.2 mg/kg (OECD TG 401, GLP) (CLH Report (2019)) (2) LD50 (analytical grade pulverized) for rats (females): 466.9 mg/kg (OECD TG 401, GLP) (CLH Report (2019)) (3) LD50 (technical grade fused) for rats (males): 715.7 mg/kg (OECD TG 401, GLP) (CLH Report (2019)) (4) LD50 (technical grade fused) for rats (females): 658.4 mg/kg (OECD TG 401, GLP) (CLH Report (2019)) (5) LD50 (technical grade pulverized) for rats: 267.5 mg/kg (males: 313.8 mg/kg, females: 221.1 mg/kg) (OECD TG 401, GLP) (CLH Report (2019), ECHA RAC Opinion (2020)) (6) LD50 for rats (males): 314 to 716 mg/kg (OECD TG 401) (AICIS IMAP (2016)) (7) LD50 for rats (females): 221 to 658 mg/kg (OECD TG 401) (AICIS IMAP (2016))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, the category was decided by adopting highly reliable data. Based on the new findings, the classification result was changed. [Evidence Data] (1) LD50 for rats in three studies: > 2,500mg/kg (OECD TG 402, GLP) (CLH Report (2019), AICIS IMAP (2016)) [Reference Data, etc.] (2) LD50 for rabbits: 50 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013), AICIS IMAP (2016))
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)	Category 2	Danger	H330	P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501	[Rationale for the Classification] Based on (1) to (7), it was classified in Category 2 by adopting the category with the higher hazard. Besides, the category of this substance may differ depending on the form. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) LC50 (4 hours, powder, median particle size: 1.88 to 2.75 micro m) for rats: 0.25 mg/L (GLP) (CLH Report (2019), ECHA RAC Opinion (2020)) (2) LC50 (4 hours, dust, median particle size: 3.0 to 3.9 micro m) for rats (males) 11.09 mg/L (GLP) (CLH Report (2019)) (3) LC50 (4 hours, dust, median particle size: 3.0 to 3.9 micro m) for rats (females): 4.29 mg/L (GLP) (CLH Report (2019)) (4) LC50 (4 hours, dust, median particle size: 10.5 micro m) for rats (males): 16.19 mg/L (GLP) (CLH Report (2019)) (5) LC50 (4 hours, dust, median particle size: 10.5 micro m) for rats (females): 4.04 mg/L (GLP) (CLH Report (2019)) (6) LC50 (4 hours, dust, median particle size: 2.9 micro m) for rats (males): 4.40 mg/L (GLP) (CLH Report (2019)) (7) LC50 (4 hours, dust, median particle size: 2.9 micro m) for rats (females): 2.21 mg/L (GLP) (CLH Report (2019))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) and (2), it was classified as "Not classified." Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in an in vitro skin irritation test (equivalent to OECD TG439, GLP), the cell viability was 88.2% (AICIS IMAP (2016), REACH registration dossier (Accessed Dec. 2021)). (2) It was reported that, in skin patch testing in 100 volunteers administered with this substance in petrolatum at 1, 2 or 10 %, no skin irritation was observed (AICIS IMAP (2016)). [Reference Data, etc.] (3) This substance irritates the eyes, skin, and respiratory tract, and when inhaled at high concentrations, it can cause lung edema, bronchitis, or bronchospasm. When it gets on the skin, it causes reddening, burning sensations, or pains, and upon contact with the eye, it causes pains, reddening, or conjunctivitis (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1. Also, based on the new findings, the classification result was changed. [Evidence Data] (1) It was reported that, in an acute eye irritation/corrosion test (OECD TG 405, GLP) with rabbits (n=3), the test was discontinued on day 5 or 6 due to severity of the eye lesions, and the effects were not reversible (corneal opacity score: 2/2.7/2.7, iritis score: 1.3/2/1.7, conjunctival redness score: 2.3/3/3, conjunctival chemosis score: 2/2/2) (AICIS IMAP (2016), REACH registration dossier (Accessed Dec. 2021)). (2) Numerous reports have documented conjunctivitis and a burning sensation of the eyes in workers exposed to this substance as dust or fumes (AICIS IMAP (2016)). [Reference Data, etc.] (3) This substance irritates the eye, skin, and respiratory tract, and when inhaled at high concentrations, it can cause lung edema, bronchitis, or bronchospasm. When it gets on the skin, it causes reddening, burning sensations, or pains, and upon contact with the eye, it causes pains, reddening, or conjunctivitis (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013)).
4	Respiratory sensitization	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), respiratory symptoms by exposure to this substance were considered to be due to respiratory tract irritation, and therefore, it was classified as "Not classified." Also, based on the new findings, the classification result was changed. [Evidence Data] (1) In a pulmonary function test after 26-week inhalation exposure of monkeys (n=8 or 9 animals/group) to this substance (concentration: 0.1 or 1.1 mg/m3 every other day, 0.5 mg/m3 every day, 6 hours/day, 5 days/week), there was no increase in pulmonary reactivity to the challenge compared to the control group at any exposure concentration, and instead, a trend towards a decrease in pulmonary reactivity was observed. As acute effects after the pre-exposure challenge with this substance (0.5 and 3 mg/m3), concentration-dependent impairment in pulmonary function (airway obstructive changes: increased airway resistance and decreased flow) was observed. Analysis of respiratory tract cells recovered from the bronchoalveolar lavage fluid demonstrated that airway obstruction was accompanied by an influx of inflammatory cells into the lung. IgG and IgE analysis results did not suggest allergic sensitization. Based on the above, it was considered that the effects observed after exposure did also not suggest respiratory tract sensitization but were due to respiratory tract irritation (ECHA RAC Opinion (2020), CLH Report (2019)). (2) In a cross-sectional case-control study for workers exposed to this substance, self-reported subjective symptoms of respiratory tract irritation were observed with clear signs of inflammation. However, as the number of eosinophils was not significantly changed in the exposed group, these effects were not considered as related to allergy (ECHA RAC Opinion (2020), CLH Report (2019)). (3) A case-control study with a limited number of workers from a vanadium plant in South Africa observed respiratory symptoms (cough and breathing difficulties) in exposed workers without significant difference of the IgE level between cases versus controls (ECHA RAC Opinion (2020), CLH Report (2019)). (4) Based on the animal study data and human epidemiological study data, respiratory sensitization of this substance could not be confirmed (ECHA RAC Opinion (2020), CLH Report (2019)).
4	Skin sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
5	Germ cell mutagenicity	Category 2	Warning	H341	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (4), the dominant lethal test with positive result, which was used as evidence for the previous classification, was less reliable, and therefore, it was judged to be Category 2. Besides, based on the new assessment, the classification result was changed. [Evidence Data] (1) As for in vivo, positive results were obtained in a dominant lethal test with mice (intraperitoneal injection, 8.5 mg/kg, 60 days (administration every 3 days)), and two comet assays with mice (single intraperitoneal injection, 5.75 to 23 mg/kg) using multiple organs (lung, kidney, spleen, heart, liver, bone marrow) and the testis, and negative results were obtained in all of micronucleus tests using the peripheral blood of rats in the oral (gavage administration, 30 to 120 mg/kg) and inhalation (1 to 16 mg/m3, 3 months) routes, a genetic damage test (inhalation exposure, 0.1 to 1 mg/m3, 16 days) using the lung tissue of mice, and a cell gene mutation test (inhalation exposure, 0.1, 1 mg/m3, 4 or 8 weeks) using transgenic mice (CLH Report (2019), ECHA RAC Opinion (2020)). (2) As for in vitro, positive results were obtained in micronucleus tests using the human peripheral blood lymphocyte cells and the Chinese hamster V79 cells, negative results were obtained in a bacterial reverse mutation test, negative results were obtained in gene mutation tests using the mouse lymphoma cell L5178Y and the Chinese hamster V79 cells, and negative results were obtained in a micronucleus test using the Syrian hamster embryo cells. Furthermore, in comet assays using the human nasal epithelia and human lymphocytes, positive results were obtained for lymphocytes, and negative results were obtained for nasal mucosa epithelia, and in a study of induction of aneuploidy using the human primary lymphocytes, disruption of microtubules in spindle apparatus, inhibition of tubulin polymerization, etc. were observed (CLH Report (2019), ECHA RAC Opinion (2020)). (3) The CLP classification proposer proposed the change from the existing Category Muta. 2 to 1B. The dominant lethality test with positive result was performed with intraperitoneal injection which is considered as non-physiological route of exposure. Even if it can be argued that intraperitoneal administration excessively maximizes systemic exposure, it is generally recognized that there is no threshold for mutagenicity unless there is specific proof for the existence of such a threshold. In addition, a comet assay, conducted by intraperitoneal route, showed positive results in testis of male mice. Positive results were also obtained in somatic cells in an in vivo micronucleus assay performed by inhalation and in an in vivo comet assay by intraperitoneal route. In experimental animal studies, distribution of 48V-labelled pentavalent and tetravalent vanadium compounds to the testes after intra-tracheal route of exposure, and increased vanadium concentration in testes observed after inhalation or oral exposure were highlighted (CLH Report (2019)). (4) As for this substance, there is one report of an in vivo germ cell mutagenicity test in mice (dominant lethal study) showing positive response. Positive results were also obtained in a comet assay in testicular cells as findings of germ cell mutagenicity. Another study performed by the same authors also reported positive results in a comet assay in different tissues. All of these studies were performed using repeated i.p. administration, and included several deficiencies in the study conduct and reporting, which question the reliability of the study. In addition, i.p. administration is known to result in high local peritoneal and testicular concentrations of the applied substance. High quality in vivo studies in somatic cells using physiological routes of exposure (oral or inhalation) have been generally negative. The RAC did not approve the change to Muta. 1B mentioned in (3), and concluded that Muta. 2 should be retained (ECHA RAC Opinion (2020)). [Reference Data, etc.] (5) As for the assessment by the EU CLP classification, reliability assessment is conducted for individual test data, and only the data of a reliability rank (Klimish score) of 1 or 2 are assessed. (6) In the EU CLP classification, it was classified as Muta. 2 (EU CLP Classification Results (Accessed November 2021)).
6	Carcinogenicity	Category 1B	Danger	H350	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) to (2), in a reliable test, although an increase in tumors including malignant ones were observed both in males and females of only one animal species (mice), there was considerable evidence of carcinogenicity in animal experiments, and therefore, it was classified in Category 1B. Besides, based on the new assessment, classification result was changed. [Evidence Data] (1) In a carcinogenicity study by 2-year inhalation exposure with rats (0.5 to 2 mg/m3, 6 hours/day, 5 days/week), there was no statistically significant increase in lung tumors in either males or females. However, in males, an increase in the incidence of alveolar/bronchiolar adenoma, alveolar/bronchiolar carcinoma, and the sum of alveolar/bronchiolar adenoma and carcinoma that exceeded the range of background data was observed, and it was judged that there was some evidence of carcinogenicity. In females, an increase in the incidence of alveolar/bronchiolar adenoma that exceeded the range of background data was observed in a low-concentration group, but the incidence of lung tumor as a whole was within the background data, and was judged to be equivocal evidence of carcinogenicity (IARC 86 (2006), AICIS IMAP (2016), CLH Report (2019), NTP TR507 (2002)). (2) In a carcinogenicity study by 2-year inhalation exposure with mice (1 to 4 mg/m3, 6 hours/day, 5 days/week), a significant increase in the incidence of lung tumors (alveolar/bronchiolar adenoma, alveolar/bronchiolar carcinoma, the sum of alveolar/bronchiolar adenoma and carcinoma) was observed both in males and females, and it was judged that there was clear evidence of carcinogenicity both in males and females (IARC 86 (2006), AICIS IMAP (2016), CLH Report (2019), NTP TR507 (2002)). (3) As for the classification results by domestic and international organizations, the IARC classified this substance in Group 2B (IARC 86 (2006)), the Japan Society For Occupational Health (JSOH) classified it in Group 2B (Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2020): proposed in 2015), the ACGIH classified it in A3 ((ACGIH (2009): proposed in 2005). Also, the EU is expected to classify this substance in Carc. 1B as the CLP classification (ECHA RAC Opinion (2020)). Furthermore, the DFG classified vanadium and its compounds in MAK Category 2 (equivalent to GHS Category 2) (List of MAK and BAT values 2020 (Accessed Nov. 2021)). [Reference Data, etc.] (4) There is no human data that can be used for the classification (ECHA RAC Opinion (2020)). (5) K-ras mutations were examined using the samples collected from the mouse lung tumors obtained in (3), and as a result, K-ras mutations were identified in 29 out of 40 samples (73%) of alveolar/bronchiolar carcinoma (background data: 30%) (ECHA RAC Opinion (2020)). (6) In an experiment examining the mode of action using the samples collected from the mouse lung tumors obtained in (3), there was no difference in the appearance level of any MAPK (mitogen activated protein kinase) between the normal lung and the lung carcinoma site, but phospho-MAPK was elevated in 5/6 samples of lung carcinoma. Out of these 5 samples, K-ras mutations and loss of heterozygosity of chromosome 6 were detected in 4/5 samples. No phospho-MAPK was detected in the carcinoma tissues without K-ras mutation or the normal lung tissues (ECHA RAC Opinion (2020)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on (1) and (2), developmental abnormalities due to exposure during the gestation period were suggested, and therefore, it was classified in Category 2. Besides, the effects observed in (3) to (4) were judged to be secondary effects. In addition, (5) to (6) were not used for the classification because the test data were obtained by a non-physiological route (intraperitoneal injection). Based on (7) and (8), although there is a concern regarding lactation effects, the information on adverse effects on fetuses is insufficient. Based on the new information source, the classification result was changed. [Evidence Data] (1) It was reported that, in a developmental toxicity study with female rats dosed by gavage (days 6 to 15 of gestation, 1 to 18 mg/kg/day), skeletal abnormalities, and lower body weight and body length were observed in fetuses at a dose at which reduced body weight gain was observed in dams (AICIS IMAP (2016)). (2) In a developmental toxicity study by intraperitoneal injection of ammonium metavanadate (CAS RN 7803-55-6) with pregnant hamsters (days 5 to 10 of gestation, 0.47 to 3.75 mg/kg), a significant increase in skeletal abnormalities (minor abnormalities) was observed at and above the lowest dose. It was reported that there was no significant difference, but meningocele, one fetus with multiple external anomalies, and a case of a molar pregnancy were observed (CLH Report (2019)). [Reference Data, etc.] (3) In a 90-day inhalation exposure test with rats, longer estrus cycle, and an increase in the frequency of diestrus were observed in females at or above 8 mg/m3. It was reported that, at 16 mg/m3, hypospermia of the testis and atypical cells of the epididymis were observed in males, but since 7/10 males died at this dose, the effects may be secondary effects (CLH Report (2019), AICIS IMAP (2016), NTP TR507 (2002)). (4) In a 90-day inhalation exposure test with mice, a decrease in epididymal sperm motility was observed in males at or above 8 mg/m3 (CLH Report (2019), AICIS IMAP (2016)). (5) It was reported that, in a dominant lethal test with male mice mated with non-exposed females after 60-day intraperitoneal injection of this substance at 8.5 mg/kg every three days, a decrease in fertility rate, impaired sperm quality (count, motility, morphology), a decrease in implantation sites, an increase in resorption per dam, a decrease in live fetuses, and an increase in dead fetuses were observed in the treated group (CLH Report (2019), AICIS IMAP (2016), NTP TR507 (2002)). (6) It was reported that, in an acute or repeated intraperitoneal injection test with male guinea pigs, in addition to a decrease in sperm motility, a decrease in sperm count, a change in sperm morphology, a dose-dependent decrease in spermatogenesis potential were observed, and by repeated dose, a decrease in spermatogonia, and alterations or destruction of seminiferous tubules of the testis, etc. were observed (CLH Report (2019)). (7) In a toxicokinetic experiment in which a single intraperitoneal injection (0.1 microg/animal) of this substance labelled with radioactive vanadium (48V) was administered to mother rats on day 2 after delivery, 34 ng/kg of vanadium (V) was detected in nursing rats milk two days after injection. Two days after administration, 48V in pups' intestines was mainly present in a chemical form of low molecular weight (LMW), but this amount decreased to 19% after 2 weeks, 80% of which was bound to high molecular fractions. 48V of low molecular fractions was presumed to represent an easily absorbed and mobile form. Tissue concentration of 48V was higher in suckling rats (10d after injection) than in weanling rats (18d after injection). It was reported that the highest radioactivity level was detected in the intestines, liver, and kidneys (ECHA RAC Opinion (2020)). (8) Based on (7), excretion of vanadium to the milk of lactating mother rats and its uptake by the suckling pups resulted in higher tissue levels of vanadium when compared to the non-exposed pups. In addition, what comes to the adverse effects caused by the exposure to vanadium via lactation, there are four test reports available suggesting neurotoxic effects in pups in a test by administration of sodium metavanadate (CAS RN 13718-26-8) to lactating rats. Although all these studies have limitations, including the use of only one dose, use of i.p. administration, and poor reporting, these together with the above information raise a concern on possible lactation effects. Although i.p. administration was not an appropriate route of exposure for assessment of fertility or developmental effects, in the case of lactational effects when suckling pups are exposed via the milk, it can be accepted in the absence of valid data. It was reported that the RAC supported the proposal by the CLP classification proposer for the addition of lactational effects (Lact.) (ECHA RAC Opinion (2020)). (9) In the EU CLP classification, it was classified as Repr. 2 (Accessed Nov. 2021)
8	Specific target organ toxicity - Single exposure	Category 1 (respiratory organs, liver, kidney)	Danger	H370	P308+P311 P260 P264 P270 P321 P405 P501	[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1 (respiratory organs, liver, kidney). [Evidence Data] (1) This substance irritates the eye, skin, and respiratory tract, and when inhaled at high concentrations, it can cause lung edema, bronchitis, or bronchospasm. When inhaled, it causes sore throat, cough, burning sensations, shortness of breath, difficulty in breathing, and wheezing (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013)). (2) In a survey for 18 workers exposed to varying degrees to dust of this substance, three of the most heavily exposed men developed symptoms in the throat (sore throat, dry cough). Examination on the third day revealed markedly inflamed throats and intense persistent coughing, but no evidence of wheezing or rales. Upon resumption of work after a 3-day exposure-free period, the symptoms returned within 0.5-4 h, with greater intensity than before, despite the use of respiratory protective equipment. After 2 weeks of the process, all 18 workers, including those primarily assigned to office and laboratory duties, developed symptoms and signs of varying degrees, including nasopharyngitis, hacking cough, and wheezing (CICAD 20 (2001)). (3) It was reported that, in three acute oral toxicity tests with rats (OECD TG 401, GLP), lethargy, ataxia (loss of control of movement), dyspnea (shortness of breath), lacrimation, diarrhea, and coma were observed, and the range of the LD50 value was 314 to 716 mg/kg (within the range for Category 2) in males and 221 to 658 mg/kg (within the range for Category 1 to Category 2) in females (AICIS IMAP (2016)). (4) It was reported that, in an acute oral toxicity test with rats, histological examination revealed necrosis of liver cells and cloudy swelling of renal tubules, and the LD50 was 86 to 137 mg/kg (within the range for Category 1) (CICAD 20 (2001)). (5) It was reported that, in an acute inhalation exposure test with monkeys (6 hours), impaired lung function (restricted and decreased air flow in central and peripheral airways, and an increase in inflammatory cells (polymorphonuclear (PMN) cells) in bronchoalveolar lavage (BAL) fluid) was observed at 5.0 mg/m3 (converted 4-hour equivalent value: 0.075 mg/L, within the range for Category 1) (AICIS IMAP (2016)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs)	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1 (respiratory organs). Besides, the effects on the liver adopted for the previous classification were not adopted for the classification because they were the findings described in the literature outside the information source list. The classification result was changed in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) In an epidemiological survey of a group of 63 workers from a company producing this substance in Finland, as a result of a comparison between the exposed group (average exposure period: 11 years, average exposure concentration: 0.36 to 0.89 mg V2O5/m3) and the control group, the exposed group complained of various symptoms in the upper respiratory tract, and as findings different from those of the control group, an increase in the number of neutrophils in nasal smears, and a significantly higher number of plasma cells in nasal mucosa samples were observed. In the second epidemiological survey, there was no difference in the pulmonary ventilation parameter in a X-ray analysis, but respiratory tract irritation (wheezing) was confirmed, and the main target organs after occupational exposure to this substance were confirmed to be respiratory organs (CLH Report (2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013)). (2) It was reported that, in a 90-day repeated inhalation (dust) exposure test with rats (6 hours/day, 5 days/week), histological alterations in the lung (such as epithelial hyperplasia, inflammation) were observed at or above 2 mg/m3 (converted guidance value: 0.0014 mg/L, within the range for Category 1), changes in pulmonary function (reduced lung compliance, changes in breathing measurements, impaired capacity to diffuse carbon monoxide, reduced static and dynamic lung volumes, and exaggerated flows), and histological alterations in the nasal cavity (such as respiratory epithelial hyperplasia, squamous metaplasia) were observed at or above 4 mg/m3 (converted guidance value: 0.0029 mg/L, within the range for Category 1) (CLH Report (2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013), AICIS IMAP (2016), NTP TR507 (2002)). (3) It was reported that, in a 90-day repeated inhalation (dust) exposure test with mice (6 hours/day, 5 days/week), effects on the lung (inflammation, epithelial hyperplasia) were observed at or above 2 mg/m3 (converted guidance value: 0.0014 mg/L, within the range for Category 1) (CLH Report (2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013), AICIS IMAP (2016), NTP TR507 (2002)). (4) It was reported that, in a 104-week repeated inhalation (dust) exposure test with rats and mice (6 hours/day, 5 days/week), in rats, effects on the lung (such as alveolar/bronchiolar hyperplasia, histiocyte infiltration in alveoli), larynx (such as chronic inflammation, degeneration and hyperplasia of the respiratory epithelium of the epiglottis), and nasal cavity (goblet cell hyperplasia of the respiratory epithelium) were observed at or above 0.5 mg/m3 (converted guidance value: 0.00036 mg/L, within the range for Category 1); and in mice, effects on the lung (such as alveolar/bronchiolar hyperplasia, chronic inflammation, histiocyte infiltration in alveoli), larynx (squamous metaplasia of the respiratory epithelium of the epiglottis), and nasal cavity (such as hyaline degeneration, squamous metaplasia of the respiratory epithelium) were observed at or above 1 mg/m3 (converted guidance value: 0.00072 mg/L, within the range for Category 1) (CLH Report (2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2013), AICIS IMAP (2016), NTP TR507 (2002)).
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)	-	- -	-	-	-
11	Hazardous to the aquatic environment Long term (Chronic)	-	- -	-	-	-
12	Hazardous to the ozone layer	-	- -	-	-	-

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.
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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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