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GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	1313-27-5
Chemical Name	Molybdenum trioxide
Substance ID	R01-B-001
Classification year (FY)	FY2019
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	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

PHYSICAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Explosives	*	- -	-	-	There are no chemical groups associated with explosive properties present in the molecule. It was classified as "Not classified (Not applicable)."
2	Flammable gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
3	Aerosols	*	- -	-	-	Not aerosol products. It was classified as "Not classified (Not applicable)."
4	Oxidizing gases	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
5	Gases under pressure	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
6	Flammable liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
7	Flammable solids	*	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2019)).
8	Self-reactive substances and mixtures	*	- -	-	-	There are no chemical groups associated with explosive or self-reactive properties present in the molecule. It was classified as "Not classified (Not applicable)."
9	Pyrophoric liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
10	Pyrophoric solids	*	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2019)).
11	Self-heating substances and mixtures	*	- -	-	-	It was classified as "Not classified" from information that it is not combustible (GESTIS (Access on May 2019)).
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	It contains a metal (Mo), but it is estimated that it does not react vigorously with water from the measurement result on water solubility: 0.49 g/1,000 mL (28 deg C) (HSDB (Access on May 2019)). Therefore, it was classified as "Not classified."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	It is an inorganic substance containing oxygen, but the classification is not possible due to no data.
15	Organic peroxides	*	- -	-	-	Inorganic substance. It was classified as "Not classified (Not applicable)."
16	Corrosive to metals	*	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	*	- -	-	-	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)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, it was classified in Category 3 in the previous classification based on (2), however, since the reliability of the original source of (2) is low, and there is a description that there was skepticism about the reliability of this LD50 in another information source (GESTIS (Access on May 2019)), it was not adopted. [Evidence Data] (1) LD50 for rats: 2,689, 2,690 mg/kg (GESTIS (Access on May 2019), ChemIDplus (Access on June 2019)) [Reference Data, etc.] (2) LD50 for rats: 125 mg/kg (DFGOT vol.18 (2002), HSDB (Access on May 2019))
1	Acute toxicity (Dermal)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) LD50 for rats: >2,000 mg/kg (GESTIS (Access on May 2019), ChemIDplus (Access on June 2019))
1	Acute toxicity (Inhalation: Gases)	*	- -	-	-	[Rationale for the Classification] Solid (GHS definition). It was classified as "Not classified (Not applicable)."
1	Acute toxicity (Inhalation: Vapours)	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
1	Acute toxicity (Inhalation: Dusts and mists)	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." Besides, an exposure concentration is higher than the saturated vapor concentration (0.0000001 mg/L), therefore, a reference value in the unit of mg/L was applied as a dust. [Evidence Data] (1) LC50 (4 hours) for rats: >5.84 mg/L (GESTIS (Access on May 2019), ChemIDplus (Access on June 2019))
2	Skin corrosion/irritation	*	- -	-	-	[Rationale for the Classification] Based on (1), it was classified as "Not classified." [Evidence Data] (1) It is reported that in a skin irritation test with rabbits according to OECD TG 404, there was no irritative response, and it was not irritating (REACH registration dossier (Access on June 2019)).
3	Serious eye damage/eye irritation	Category 2	Warning	H319	P305+P351+P338 P337+P313 P264 P280	[Rationale for the Classification] Because of the description in (1) and the fact that the powder is expected to be physically irritating to the eyes, it was judged to be Category 2. Besides, the category was changed from the previous classification. [Evidence Data] (1) There is a description that the dust of this substance irritates the eye and mucous membranes (NTP TR462 (1997)). [Reference Data, etc.] (2) It was classified in "Eye Irrit. 2 (H319)" in the EU-CLP classification (EU CLP classification (Access on May 2019)).
4	Respiratory sensitization	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	*	- -	-	-	[Rationale for the Classification] There are reports of (1)-(3), however, since they are insufficient data for judging the classification of this substance, it was classified as "Classification not possible." [Reference Data, etc.] (1) In multiple patch tests in humans in which this substance was applied to patients with stainless steel stents, etc., there are reports of positive results at a low rate (ATSDR (2017)). (2) There are positive reports in sensitization tests (maximization method) of sodium molybdate (CAS RN 7631-95-0) or molybdenum pentachloride (CAS RN 10241-05-1) with guinea pigs (ATSDR (2017), DFGOT vol.18 (2002)). (3) Although details of the test results are unknown, there are negative reports in a sensitization test (maximization method) of sodium molybdate with guinea pigs and a local lymph node assay (LLNA) of molybdenum pentachloride with C58Bl/6 mice (DFGOT vol.18 (2002)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data. [Evidence Data] (1) As for in vivo, there are no data for this substance. (2) As for in vitro, there are negative reports in a bacterial reverse mutation test, a chromosomal aberration test and a sister chromatid exchange test with cultured mammalian cells (NTP TR462 (1997), ATSDR (2017), DFGOT vol.18 (2002), IARC 118 (2018), Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012), ACGIH (7th, 2003)), and a positive report in a mammalian cell micronucleus test (ATSDR (2017), Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012), ACGIH (7th, 2003)). [Reference Data, etc.] (3) There are positive reports for sodium molybdate (CAS RN 7631-95-0), a soluble molybdenum compound, in a dominant lethal test with mice dosed intraperitoneally and a mouse bone marrow micronucleus test by intraperitoneal administration (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012), ATSDR (2017)). Both results are reported to be weakly positive in ATSDR. Additionally, the authors of the original source concluded that since these were preliminary data in pilot experiments, definite conclusion could not be reached (ACGIH (7th, 2003), Titenko-Holland et. al., Environ Mol Mutagen 32: 251-259 (1998)). (4) As for in vitro tests on soluble molybdenum salts (details were unknown), there is a negative report in a bacterial reverse mutation test (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)). (5) There is a positive report on sodium molybdate in an in vitro mammalian cell micronucleus test (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)). (6) As for in vitro, there are positive reports of hexaammonium heptamolybdate (CAS RN 12027-67-7) or sodium molybdate in a chromosomal aberration test and a sister chromatid exchange test with cultured mammalian cells (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)). Besides, it is reported that hexaammonium heptamolybdate was positive in a mammalian cell micronucleus test in Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012), however, it is reported as a result of ammonium molybdate in ACGIH (7th, 2003) (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012), ACGIH (7th, 2003)). (7) An increased incidence of chromosomal aberrations is reported in human peripheral blood lymphocytes from persons occupationally exposed to molybdenum (CAS RN 7439-98-7), molybdenum disulphide (MoS2, CAS RN 1317-33-5), ammonium paramolybdate (hexaammonium heptamolybdate) and this substance (DFGOT vol.18 (2002)). (8) Phosphomolybdic acid (CAS RN 12026-57-2) and sodium molybdate, which are soluble molybdenum compounds, were classified in Category 2 in the GHS classification in FY 2016 and FY2015, respectively. On the other hand, ammonium molybdate (CAS RN 12027-67-7), which is also a soluble molybdenum compound, was classified as "Classification not possible" in the GHS classification in FY 2015.
6	Carcinogenicity	Category 2	Warning	H351	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] Based on classification results by other organizations in (1), it was classified in Category 2 in accordance with the GHS Classification Guidance for the Japanese Government. [Evidence Data] (1) As for classification results by domestic and international organizations, it was classified in Group 2B by IARC (IARC 118 (2018)), Carc. 2 in the EU CLP classification (EU CLP classification (Access on May 2019)), A3 by ACGIH (ACGIH (7th, 2003)), and Group 2B by the Japan Society for Occupational Health (JSOH) (Recommendation of Occupational Exposure Limits (proposed in 2017)). [Reference Data, etc.] (2) In a carcinogenicity study (10, 30, 100 mg/m3) with mice by inhalation exposure for 2 years, significantly increased incidences of alveolar/bronchiolar carcinoma and alveolar/bronchiolar adenoma or carcinoma in male, and significantly increased incidences of alveolar/bronchiolar adenoma and alveolar/bronchiolar adenoma or carcinoma in female were observed. From these, it was concluded that there was some evidence of carcinogenic activity from this substance in both female and male mice (NTP TR462 (1997)). (3) In a carcinogenicity study (10, 30, 100 mg/m3) with rats by inhalation exposure for 2 years, no tumor with a significantly increased incidence was observed (NTP TR462 (1997)). (4) In a case-control study of 478 male lung cancer patients and 536 male patients without lung cancer or lung disease as controls in Belgium, occupational exposures to 16 suspected carcinogens including molybdenum were classified based on self-reported data, where the calculated odds ratios for lung cancer were significantly high as much as 2.1 for molybdenum, 1.7 for mineral oils, and 1.4 for chromium. Since the odds ratio for molybdenum was the highest, the author claimed that this is the first study ever to recognize the association between exposure to molybdenum and lung cancer. Measurement of the concentrations in the air, however, was not performed, and the concrete types and concentrations of the exposed substances were unknown (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)).
7	Reproductive toxicity	Category 2	Warning	H361	P308+P313 P201 P202 P280 P405 P501	[Rationale for the Classification] There is no information on this substance. Although the water solubility of this substance is 0.49 g/1,000 mL (28 deg C) and not high (HSDB (Access on May 2019)), as shown in (1), as it is demonstrated that more than 50% is absorbed via the oral route, it was judged that it is possible to classify this substance based on the information of soluble molybdenum compounds. Based on (2) and (3), since it was considered that it may cause adverse effects on sexual function and fertility in experimental animals, it was classified in Category 2. Besides, by adding the information on soluble molybdenum compounds and reviewing the classification, the category was changed from the previous classification. [Evidence Data] (1) When this substance labeled with 99Mo was administered to rats by gavage, 26% of the dose after 6 hours and 51% after 12 hours were excreted in the urine, and after 24 hours, 58% in the urine and 8% in the feces were excreted. On the other hand, when insoluble molybdenum disulphide (CAS RN 1317-33-5) was orally administered to guinea pigs, no significant changes in molybdenum concentrations in organs other than the lung were observed, and it is assumed not to be absorbed from the gastrointestinal tract (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)). (2) In a test in which female rats were dosed with sodium molybdate dihydrate (CAS RN 10102-40-6) (water solubility is 654.2 g/1,000 mL (20 deg C) (SIAP (2013))) by drinking water for 6 weeks followed by mating with untreated male and continuous dosing by a gestational Day 21, prolonged estrus cycle, decreased body weight gain in maternal animals, low fetal body weight, decreased tendency of the number of fetuses, increases in fetal resorptions and developmental delay of the organs in fetuses were observed (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)). (3) When female and male rats were dosed with sodium molybdate dihydrate by feeding for 13 weeks followed by mating, a decrease in the fertility index was observed at or above 80 ppm (approx. 8 mg/kg/day). When the males of the infertile pairs were mated with untreated females, no pregnant females were found, so the cause of infertility is considered to be on the male side. Degeneration of the seminiferous tubules was observed in the testis of those males (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)). [Reference Data, etc.] (4) In tests in which mice and rats were exposed to this substance by inhalation for 13 weeks, no effects on the weights or tissues of the reproductive organs in males and females, or sperm counts or motility in males were observed (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)).
8	Specific target organ toxicity - Single exposure	Category 3 (Respiratory tract irritation)	Warning	H335	P304+P340 P403+P233 P261 P271 P312 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 3 (respiratory tract irritation). The heart, kidney and liver were adopted as the target organs in the previous classification based on the information in (3), however, it is reported in (4) that no effects were observed at concentrations approximately 100 times higher than that in (3). Since the details of both tests are unknown, they were not adopted as the rationale. Therefore, classification results were changed. [Evidence Data] (1) There is a description that exposure to this substance produces irritation of the mucous membranes of the nose and throat (HSDB (Access on May 2019)). (2) This substance is regarded as a soluble molybdenum compound in ACGIH (7th, 2003). As for ammonium molybdate (CAS RN 12027-67-7), another soluble molybdenum compound, it is reported that in a single inhalation exposure test with rats, 1-hour exposure to the dust at 3,000-5,000 mg/m3 caused irritation of the upper respiratory tract and conjunctiva (ACGIH (7th, 2003), DFGOT vol.18 (2002)). [Reference Data, etc.] (3) It is reported that in a 2-hour single inhalation exposure test with rats, dystrophic changes in the heart, kidneys and liver were observed 2 weeks after exposure to the aerosol of this substance at 64 mg/m3 (converted 4-hour equivalent value: 0.032 mg/L), but no effect on the body weight was observed (DFGOT vol.18 (2002)). (4) It is reported that in a 1-hour single inhalation exposure test with rats, no effect was observed during the 4-week observation period after exposure to the dust of this substance at 12,000-15,000 mg/m3 (converted 4-hour equivalent value: 3.0-3.75 mg/L) (ACGIH (7th, 2003), DFGOT vol.18 (2002)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs, reproductive organs (male)), Category 2 (kidney)	Danger Warning	H372 H373	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1)-(3), findings suggesting effects on the lungs were observed in humans via the inhalation route, and effects on the respiratory organs were observed from the range of Category 1 in experimental animals. Effects via the oral route are considered to be the effects due to molybdate ions, so the use of information on sodium molybdate and ammonium molybdate which are soluble molybdenum was judged as reasonable. Based on (4) and (5), as soluble molybdenum, systemic effects and effects on the testis from the range of Category 1, and the effects on the kidneys within the range of Category 2 via the oral route were presumable. Therefore, it was classified in Category 1 (respiratory organs, reproductive organs (men)), Category 2 (kidney). Besides, by adding the new information sources to the information sources of the previous classification, the target organs were reviewed. [Evidence Data] (1) As for human data, of 19 persons who had been exposed to this substance at concentrations of 1 to 25 mg/m3 for 4 to 7 years, 3 suffered from respiratory difficulties and frequent coughing. They were diagnosed as early stage pneumoconiosis by x ray (DFGOT vol.18 (2002)). (2) When rats were exposed to this substance by inhalation at 10 to 100 mg/m3 for 2 years, as non-neoplastic lesions, hyaline degeneration of the nasal olfactory and respiratory epithelium, and squamous metaplasia of the epiglottis at or above 10 mg/m3 (0.01 mg/L, within the range of Category 1), and chronic alveolar inflammation at or above 30 mg/m3 (0.03 mg/L, within the range of Category 2) were observed (NTP TR462 (1997), Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012), DFGOT vol.18 (2002), ACGIH (7th, 2003), IARC 118 (2018), ATSDR (2017)). (3) When mice were exposed to this substance by inhalation at 10 to 100 mg/m3 for 2 years, as non-neoplastic lesions, squamous metaplasia of the epiglottis, histiocyte infiltration in the lungs and alveolar epithelial metaplasia at or above 10 mg/m3 (0.01 mg/L, within the range of Category 1), nasal suppurative inflammation at or above 30 mg/m3 (0.03 mg/L, within the range of Category 2), and atrophy of the olfactory epithelium, hyaline degeneration of the nasal olfactory and respiratory epithelium, laryngeal epithelial hyperplasia at 100 mg/m3 (0.1 mg/L, within the range of Category 2) were observed (same as the above). (4) In the FY2015 GHS classification for sodium molybdate (CAS RN: 7631-95-0), it was classified in Category 1 (systemic toxicity, testis), Category 2 (kidney) based on information that in a 4-week test with rats by diet administration of disodium molybdate dihydrate (CAS number: 10102-40-6), besides deaths, only extreme emaciation and decreased body weight caused by increased excretion of copper from bodies due to molybdenum administration were observed, and at 0.05% (about 25 mg/kg/day) (converted guidance value: 7.78 mg/kg/day, within the range of Category 1), decreased body weight was found (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)), and that in a 13-week test with rats by diet administration of disodium molybdate dehydrate, degeneration of the seminiferous tubules in the testis was observed in males at 0.008% (8 mg/kg/day, within the range of Category 1) (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)), and that in a 90-day test with rats by gavage administration of disodium molybdate dehydrate, weight gain reduction and slight diffuse hyperplasia of the proximal tubules were found at 60 mg/kg/day within the range of Category 2, and reversibility was observed (SIAP (2013)). Among these, converted values equivalent to this substance of the dose at which systemic effects or effects on the testis were observed were 4.62 mg/kg/day and 5 mg/kg/day, respectively, which were within the range of Category 1, and a converted value equivalent to this substance of the dose at which effects on the kidneys were observed was 36 mg/kg/day, which was within the range of Category 2. (5) In the FY2015 GHS classification for ammonium molybdate (CAS RN 12027-67-7), it was classified in Category 2 (kidney) because there were no organic changes but function effects in the kidney in the following test, and changes in the kidney were observed for sodium molybdate, an analog substance. In an 8-week gavage administration toxicity test with rats, reduced weight gain, decreased absolute kidney weight, increased relative kidney weight, increased urine volume, increased creatinine in the urine, reduced creatinine clearance, and increased excretion of urinary deviation enzyme (kallikrein) from the distal tubules were observed at 80 mg/kg/day (converted guidance value: about 50 mg/kg/day, within the range of Category 2) (Environmental Risk Assessment for Chemical Substances Vol.10 (Ministry of the Environment, 2012)).
10	Aspiration hazard	*	- -	-	-	[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)	Not classified	- -	-	-	It was classified as "Not classified" from 96-hour LC50 = 180 mg/L for crustacea (Americamysis bahia) (Environmental Risk Assessment for Chemical Substances Vol. 10 (Ministry of the Environment, 2012)).
11	Hazardous to the aquatic environment Long term (Chronic)	Not classified	- -	-	-	Reliable chronic toxicity data on this substance were not obtained, but chronic toxicity data were obtained on disodium molybdate(VI) and disodium molybdate(VI) dihydrate, both of which generate a molybdate ion in water like this substance. Despite unknown environmental dynamics of the inorganic compound, if chronic toxicity data for these are used, it was classified as "Not classified" because all of chronic toxicity NOEC for plants, crustacea, and fish were > 1 mg/L (Environmental Risk Assessment for Chemical Substances Vol. 10 (Ministry of the Environment, 2012)).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	Classification not possible due to lack of data.

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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