GHS Classification Results by the Japanese Government
GENERAL INFORMATION
REFERENCE INFORMATION
PHYSICAL HAZARDS
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS
NOTE:
GENERAL INFORMATION
| Item | Information |
|---|---|
| CAS RN | 111-30-8 |
| Chemical Name | Glutaraldehyde |
| Substance ID | R03-B-008-METI, MOE |
| Classification year (FY) | FY2021 |
| 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 | FY2009 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 |
| 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) |
- |
- | - | Liquid (GHS definition) |
| 3 | Aerosols | Not classified (Not applicable) |
- |
- | - | Not aerosol products. |
| 4 | Oxidizing gases | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 5 | Gases under pressure | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 6 | Flammable liquids | Category 4 |
Warning |
H227 | P370+P378 P210 P280 P403 P501 |
It was classified in Category 4 based on a flash point of 71 deg C (GESTIS (Accessed July 2021)). |
| 7 | Flammable solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 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 |
- |
- | - | It is estimated that it does not ignite at normal temperatures from an autoignition temperature of 395 deg C (REACH registration dossier (Accessed July 2021)). |
| 10 | Pyrophoric solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 11 | Self-heating substances and mixtures | Classification not possible |
- |
- | - | Test methods applicable to liquid substances are not available. |
| 12 | Substances and mixtures which, in contact with water, emit flammable gases | Not classified (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 classified (Not applicable) |
- |
- | - | The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. |
| 14 | Oxidizing solids | Not classified (Not applicable) |
- |
- | - | Liquid (GHS definition) |
| 15 | Organic peroxides | Not classified (Not applicable) |
- |
- | - | Organic compounds containing no bivalent -O-O- structure in the molecule. |
| 16 | Corrosive to metals | Classification not possible |
- |
- | - | No data available. |
| 17 | Desensitized explosives | Not classified (Not applicable) |
- |
- | - | There are no chemical groups associated with explosive properties present in the molecule. |
| 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 (5), it was classified in Category 3. [Evidence Data] (1) LD50 for rats (males): 123 mg/kg (OECD TG 401, GLP) (CLH Report (2013), SIAR (2001), AICIS (1994)) (2) LD50 for rats (females): 77 mg/kg (OECD TG 401, GLP) (CLH Report (2013), SIAR (2001), AICIS (1994)) (3) LD50 for rats (males): 158 mg/kg (CLH Report (2013), SIAR (2001)) (4) LD50 for rats (females): 143 mg/kg (CLH Report (2013), SIAR (2001)) (5) LD50 for rats: between 134 to 140 mg/kg (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)) |
| 1 | Acute toxicity (Dermal) | Category 3 |
Danger |
H311 | P302+P352 P361+P364 P280 P312 P321 P405 P501 |
[Rationale for the Classification] Based on (1) to (5), it was classified in Category 3. The classification was changed because a new information source was added. [Evidence Data] (1) LD50 for rabbits: 403 mg/kg (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)) (2) LD50 for rabbits (males): 875 mg/kg (CLH Report (2013)) (3) LD50 for rabbits: between 640 to 2,000 mg/kg (AICIS (1994), SIAR (2001)) (4) LD50 for rabbits (males): 900 mg/kg (AICIS (1994)) (5) LD50 for rabbits (males): 1,430 mg/kg (AICIS (1994)) [Reference Data, etc.] (6) LD50 for rabbits: > 1,000 mg/kg (CLH Report (2013), EPA Pesticides (2007)) (7) LD50 for rats: > 1,000 mg/kg (CLH Report (2013), DFG MAK (1997)) |
| 1 | Acute toxicity (Inhalation: Gases) | Not classified |
- |
- | - | [Rationale for the Classification] Liquid (GHS definition). It was classified as "Not classified." |
| 1 | Acute toxicity (Inhalation: Vapours) | Category 1 |
Danger |
H330 | P304+P340 P403+P233 P260 P271 P284 P310 P320 P405 P501 |
[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1. Also, since the exposure concentration was lower than 90% (19,541 ppm) of the saturated vapor pressure concentration, it was judged to be in a vapor state and classified based on the reference value in units of ppmV. [Evidence Data] (1) LC50 (4 hours) for rats (males): 23.5 ppm (OECD TG 403, GLP) (AICIS (1994)) (2) LC50 (4 hours) for rats (females): 40.1 ppm (OECD TG 403, GLP) (AICIS (1994)) (3) LC50 (4 hours) for rats: > 24.4 ppm ( >0.11mg/L) (OECD TG 403, GLP) (CLH Report(2013)) (4) LC50 (4 hours) for rats: between 23.5 to 44.4 ppm (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)) [Reference Data, etc.] (5) LC50 (4 hours) for rats (females): 68.4 ppm (0.28 mg/L) (CLH Report (2013)) (6) LC50 (4 hours) for rats (males): 85.5 ppm (0.35 mg/L) (CLH Report (2013)) (7) LC50 (4 hours) for rats (males): 126 ppm (0.52 mg/L) (CLH Report (2013)) (8) LC50 (4 hours) for rats (females): 110 ppm (0.45 mg/L) (CLH Report (2013)) |
| 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 1B |
 Danger |
H314 | P301+P330+P331 P303+P361+P353 P305+P351+P338 P304+P340 P260 P264 P280 P310 P321 P363 P405 P501 |
[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1B. [Evidence Data] (1) This substance showed irritation to the skin of test animals with 25% or above aqueous solutions. When it adhered to the human skin, redness and bulla were caused, and irritation to the throat and nasal mucosa was also observed. As a preventive measure against dermatitis, etc., the Ministry of Health, Labour and Welfare set the maximum value of the concentration in the air of a work environment to 0.05 ppm as a target standard (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (2) In an acute dermal irritation/corrosion test with rabbits (n=6) (OECD TG 404, GLP, 4-hour application, 10-day observation), at 24, 48, and 72 hours after application, the average erythema score was 2.8, and the average edema score was 2.6, and also in the observation after 10 days, necrosis and desquamation were observed, and there was no reversibility. It was reported that, in tests which were carried out in parallel, necrosis in 2 animals and skin desquamation in 4 animals were observed among 5 animals, which survived after exposure, in a 1-hour exposure group, and minor erythema was observed in 1 animal in a 3-minute exposure group (ECHA RAC Opinion (2014), CLH Report (2013)). (3) In a skin irritation test with rabbits (n=4) (4-hour application, 8-day observation), when a 50% aqueous solution was applied, necrosis, erythema, and edema were observed after 8 days, and effects were irreversible. It was reported that, in a skin irritation test with rabbits (n=2) (1-hour application of a 50% aqueous solution, 8-day observation), severe scaling with erythema and edema was observed after 8 days, and there was no reversibility; and in a skin irritation test with rabbits (3-minite application of a 50% aqueous solution, 8-day observation), no edema was observed, and scabs were observed after 8 days (ECHA RAC Opinion (2014), CLH Report (2013)). (4) In an acute dermal irritation/corrosion test with rabbits (n=5) (equivalent to OECD TG 404, semiocclusive), in 1 animal of a group applied with a 24% solution, after 3-minute exposure and 24-hour observation, no corrosion was observed, but after 1-hour or 4-hour exposure and 24-hour observation, corrosion was observed. In 1 animal of a group applied with a 15% solution, after 3-minute or 1-hour exposure and 72-hour observation, no corrosion was observed, but after 4-hour exposure and 72-hour observation, corrosion was observed. It was reported that, in 3 animals of a group applied with a 4% solution, after 4-hour exposure and 14-day observation, severe edema was observed (erythema/scab score: 3.3/2.7/2.7, edema score: 4/2/3) (REACH registration dossier (Accessed July 2021)). [Reference Data, etc.] (5) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Ministry of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "glutaraldehyde" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders, are designated as occupational diseases. |
| 3 | Serious eye damage/eye irritation | Category 1 |
Danger |
H318 | P305+P351+P338 P280 P310 |
[Rationale for the Classification] Based on (1) to (4), it was classified in Category 1. [Evidence Data] (1) It was classified in Category 1B for skin corrosion/irritation. (2) As for this substance, concentration-dependent irritation to the eyes was observed in test animals, and severe corneal damage was observed with an aqueous solution at or above 5%. Its contact with the human eye mucosa caused redness and pain, and its high concentrations might cause keratitis or conjunctivitis (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (3) In an eye irritation test with rabbits (n=6) (GLP, 45% solution, 21-day observation), after 24, 48, and 72 hours, the average score of corneal opacity was 4, the average conjunctival redness score was 1.7, and the average chemosis score was 3.9, and corneal opacity and conjunctival swelling were so severe that complete scoring of the findings of the cornea and iritis was not possible. It was reported that the effects were not reversible and continued until the end of the observation period of 21 days (ECHA RAC Opinion (2014), CLH Report (2013)). (4) In an eye irritation test with rabbits (n=6) (50% solution, 8-day observation), corneal opacity increased the intensity from the localized one after 24 hours, and extended to the area of 75 to 100% after 8 days. It was reported that conjunctival redness and chemosis also progressed, and the eye lids were half-closed within 8 days (corneal opacity score: 2/2/2/2/2/2.3, iritis score: 1/1/1/1/1/1, conjunctival redness score: 2/2/2.3/2/2.3/2.3, chemosis score: 2/2.6/2.3/2.3/2.3/2.3) (ECHA RAC Opinion (2014), CLH Report (2013), REACH registration dossier (Accessed July 2021)). [Reference Data, etc.] (5) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Ministry of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "glutaraldehyde" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders, are designated as occupational diseases. |
| 4 | Respiratory sensitization | Category 1A |
 Danger |
H334 | P304+P340 P342+P311 P261 P284 P501 |
[Rationale for the Classification] Based on (1) to (5), it was classified in Category 1A. [Evidence Data] (1) In humans, repeated exposure to glutaraldehyde which was used for sterilizing, etc. might cause sensitization to respiratory organs such as rhinitis, shortness of breath, noisy respiration, asthma, etc. (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (2) There were multiple reports on the respiratory sensitization, which was observed in workers occupationally exposed to this substance at high concentrations, and the sensitization might be caused at exposure concentrations of 20 to 30 ppb or above. There was also a report indicating that the incidence of asthma among workers after exposure was related to the exposure to this substance (ECHA RAC Opinion (2014), CLH Report (2013)). (3) It was reported that, in an IgE test with mice (n=6/group), 50 microL of 0%, 2.5%, 5%, and 12.5% solutions of this substance were applied, then after 7 days, 25 microL was applied, and after 14 days, serum IgE was measured, and a dose-dependent increase in serum IgE was observed (serum IgE: 0.304 ± 0.024 microg/mL (0%), 0.516 ± 0.038 microg/mL (2.5%), 0.640 ± 0.195 microg/mL (5%), 1.280 ± 0.193 microg/mL (12.5%)) (ECHA RAC Opinion (2014), CLH Report (2013)). (4) This substance was classified in occupational sensitizers to the respiratory tract Group 1 by the Japan Society For Occupational Health (JSOH). (5) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Ministry of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "glutaraldehyde" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders, are designated as occupational diseases. |
| 4 | Skin sensitization | Category 1A |
 Warning |
H317 | P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501 |
[Rationale for the Classification] Based on (1) to (8), it was classified in Category 1A. [Evidence Data] (1) It was reported that there was a report on workers who were engaged in sterilizing with glutaraldehyde and developed pruritic dermatitis, rash, or allergic contact dermatitis on the hand, arm, face, and cervix (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (2) It was reported that, in a British study of 348 nurses in 59 endoscopy divisions, 91.4% of the subjects were exposed mainly to this substance, and occupational contact dermatitis was observed in 44% of the subjects exposed to this substance (Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (3) It was reported that, in a maximization test with guinea pigs (n=20) (equivalent to OECD TG 406, GLP, intradermal induction: 0.1%), the skin sensitization rate after challenge was 68% (13/19 animals), and the skin sensitization rate after re-challenge was 32% (6/19 animals) (ECHA RAC Opinion (2014), CLH Report (2013)). (4) It was reported that, in a maximization test with guinea pigs, it showed skin sensitization (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (5) It was reported that, in a Local Lymph Node Assay (LLNA) with mice, the EC3 value was calculated to be 0.07% when acetone/olive oil was used as a solvent, and the EC3 value was calculated to be 1.5% when propylene glycol was used as a solvent (ECHA RAC Opinion (2014), CLH Report (2013)). (6) It was reported that, in a Local Lymph Node Assay (LLNA) with mice, the Stimulation Index (SI values) were 15.5 (2.5%), 23.4 (5%), 38.7(12.5%), and 34.9 (25%), respectively (ECHA RAC Opinion (2014), CLH Report (2013)). (7) This substance was classified in occupational sensitizers to the skin Group 1 by the Japan Society for Occupational Health (JSOH). (8) In the Ministry of Labour Notification No. 33 issued in 1996 (revised by the Ministry of Health, Labour and Welfare Notification No. 316 in 2013), this substance is designated as "glutaraldehyde" in simple chemical substances or compounds (including alloys) designated by the Minister of Health, Labour and Welfare based on Appended Table 1-2, (iv) 1 of the Ordinance for Enforcement of the Labor Standards Act, and diseases (skin disorders, disorders in the anterior part of the eye, respiratory tract disorders) with specific symptoms or disorders caused by occupations exposed to this substance as main symptoms or disorders, are designated as occupational diseases. |
| 5 | Germ cell mutagenicity | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." In (3), it was judged that additional tests were not necessary, and therefore, since there was no basis for classifying this substance in Category 2, it was classified as "Not classified." [Evidence Data] (1) As for in vivo, positive results were obtained only in a chromosomal aberration test with the bone marrow erythroblast of mice (exposed once by intraperitoneal injection), and negative results were obtained in all of a chromosomal aberration test with the bone marrow erythroblast of rats, a micronucleus test with the bone marrow peripheral of mice (dosed once by gavage, 13-week inhalation exposure), a micronucleus test with the bone marrow erythroblast of mice (3-day intraperitoneal injection), a dominant lethal test with mice, and an UDS test with the hepatocytes of rats (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)). (2) As for in vitro, positive results were mostly obtained in bacterial reverse mutation tests, and positive or negative results were obtained in gene mutation tests and chromosomal aberration tests using cultured mammalian cells, (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)). (3) The EU concluded that, as for genotoxicity of this substance, a strong in vitro evidence was obtained, but in vivo, negative results were obtained in all tests except for one test. The EU concluded that, although the possibility of this substance showing mutagenicity in the site of contact remained, negative results were obtained in a carcinogenicity study and a reproduction toxicity study, and therefore, additional tests were not necessary (CLH Report (2013)). (4) The Ministry of Health, Labour and Welfare also indicated that mutagenicity of this substance could not be judged (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)). Also, since positive results were obtained in a mutagenicity test for this substance, this substance was considered to be the target substance of the guidelines to prevent the impairment of health (mutagenicity) of the Industrial Safety and Health Act (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019)). |
| 6 | Carcinogenicity | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) to (3), it was classified as "Not classified." [Evidence Data] (1) As for the classification results by domestic and international organizations, the ACGIH classified this substance in A4 (ACGIH (7th, 2015)), the EPA classified it in NL (Not Likely to be Carcinogenic to Humans) (EPA OPP Annual Cancer Report 2020 (Accessed July 2021): classification in 2006), and the DFG classified it in Category 4 (DFG MAK (2006)). (2) In a carcinogenicity study with rats dosed by drinking water for two years, an increase in the incidence of large granular lymphocyte leukemia was observed in females, but since the disease was a geriatric spontaneous tumor and not dose-dependent in rats, the toxicological significance was not clear (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (3) In any of the three carcinogenicity studies by 78-week inhalation exposure with mice, and by 104-week inhalation exposure with mice and rats, there was no increase in the incidence of tumors related to exposure (same as above, NTP TR490 (1999)). [Reference Data, etc.] (4) In a cohort study, which targeted 186 male employees in a plant manufacturing this substance in the U.S., the mortality was 14/186 persons (SMR = 0.55, p = 0.15), the cancer mortality was 4/186 persons (SMR = 0.65, p = 0.59), and there was no excessive incidence of cancer due to the exposure to this substance. It was reported that, as a result of a study by comparing 188 persons of this cohort, including some replaced workers, to 3,173 persons of the control group (workers of non-exposure divisions), the cancer mortality was lower than the expected value also in a group exposed to higher than 100 ppb/year, there was no specific tumor which showed a tendency of an increase with increased exposure, and there were also no dead persons due to leukemia, or cancer in the nasal cavity or epipharynx (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2019), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017), Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (5) As there was evidence of genotoxic effects in vitro, and the incidence of cell proliferation after inhalation exposure for thirteen weeks increased in the epithelium of the nasal cavity, potential carcinogenic effects of this substance on the respiratory tract could not be excluded (at concentrations which did not lead to respiratory tract irritation, however, no cell proliferation was caused, and genotoxic effects played only a minor role), and therefore, the DFG classified it in Category 4 (DFG MAK (2006)). |
| 7 | Reproductive toxicity | Not classified |
- |
- | - | [Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) In a cohort study, which targeted all nurses who were engaged in sterilizing in a hospital in Finland, the incidence of spontaneous abortions in nurses (545 persons) engaged in sterilizing during the pregnancy period was 15.1%, which was significantly higher than the incidence of 10.5% in the control group (1,179 persons). As a result of examining the relationship between the disinfectant to which nurses were exposed and the spontaneous abortions, there was no relationship with spontaneous abortions in any exposure to glutaraldehyde before and during the pregnancy (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (2) It was reported that, in a case-control study which targeted 217 nurses and 46 persons who had spontaneous abortions or delivered malformed infants in Finland, the odds ratios of spontaneous abortions and delivery of malformed infants to exposure to glutaraldehyde were 1.1 and 0.8 respectively, and there was no increase in these risks due to exposure to glutaraldehyde (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (3) It was reported that, in a two-generation reproduction toxicity study with rats by oral administration, no reproduction toxicity was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017), ACGIH (7th, 2015)). (4) It was reported that, in four developmental toxicity studies by oral administration (dosed by gavage or drinking water) with pregnant animals (mice, rats, and rabbits), no developmental toxicity was observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017), ACGIH (7th, 2015)). |
| 8 | Specific target organ toxicity - Single exposure | Category 1 (respiratory organs) |
Danger |
H370 | P308+P311 P260 P264 P270 P321 P405 P501 |
[Rationale for the Classification] Based on (1) to (4), irritation mainly to the nose, throat, etc. was observed in humans. Based on (5) to (10), effects on the central nervous system, nose, lung, etc. were observed in animal studies. However, effects on the central nervous system were considered to be due to systemic effects. Based on the above, considering the effects in human and animal studies comprehensively, it was classified in Category 1 (respiratory organs). [Evidence Data] (1) It was reported that, among 44 employees who used glutaraldehyde once or more a week in a hospital, 64% complained of irritation to the eyes and nose, 41% complained of irritation to the throat, and 16% complained of sore throat (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (2) It was reported that, as the evidence of respiratory tract irritation due to occupational exposure, there were symptoms in the nose and respiratory tract such as sneezing, runny nose, coughing, pharynx irritation, tingling in the throat, etc. (CLH Report (2013)). (3) It was reported that systemic effects related to this substance other than respiratory tract irritation were headache, dizziness, nausea, abdominal pain, numbness of the limbs, and cardiac effects (palpitation, tachycardia) (EPA Pesticides (2007)). (4) It was reported that, as an accidental case in humans, symptoms such as fever, vomiting, tachypnea, tachycardia, etc. were observed from 6 hours after exposure in a child whose face was exposed to 100 mL of glutaraldehyde (Cidex) by mistake during surgery, but the child finally recovered without sequelae (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Recommendation of Occupational Exposure Limits (Japan Society For Occupational Health (JSOH), 2006)). (5) It was reported that, in an acute oral toxicity test with rats, crouching posture, reduced locomotor activity, gait abnormality, panting, piloerection, abdominal bloating, ptosis, reddish tears, hemorrhage in the nasal mucosa, diarrhea, pulmonary hyperemia, and erosion in the glandular stomach were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). (6) It was reported that, in an acute dermal toxicity test with rats, dyspnea, apathy, excitation, staggering, atony, trembling, and poor general state were observed at 200 to 1000 mg/kg (within the range for Category 1) (CLH Report (2013)). (7) It was reported that, in an inhalation exposure test with rats, reduced locomotor activity, increases in grooming and face washing, a decrease in respiratory rate, lacrimation, ptosis and epistaxis, and lung congestion and emphysema were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2009)). (8) It was reported that, in an acute inhalation toxicity test with rats, as a result of necropsy, rhinitis, and goblet cell hyperplasia in the nasal cavity were observed at 0.11mg/L (within the range for Category 1) (CLH Report (2013)). (9) It was reported that, in an acute inhalation toxicity test with rats, breathing difficulties were observed in most animals, and color changes of the lung were observed at 0.094 mg/L (within the range for Category 1) and 0.17 mg/L (within the range for Category 1), and the cause of death was considered to be lung damage (AICIS (1994)). (10) It was reported that, in a dermal toxicity test with rabbits, increases in grooming and face washing, rales, and yellowed fur were observed (Initial Risk Assessment Report (NITE, CERI, NEDO, 2010)). [Reference Data, etc.] (11) It was reported that, in an acute oral toxicity test with rats, mice, and guinea pigs, the animals showed symptoms of depressive effects to the CNS, cramps, and difficulty in breathing (GESTIS (Accessed July 2021)). |
| 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 (3), symptoms were observed mainly in the respiratory organs such as the nose, throat, etc. in humans. In animal studies, based on (4) to (8), symptoms were observed in the nose, lung, etc. within the range for Category 1 in the inhalation route. Based on the above, it was classified in Category 1 (respiratory organs). [Evidence Data] (1) It was reported that, in a cross study which targeted 39 Swedish hospital staff who were engaged in sterilizing with a 2% glutaraldehyde solution once or more a month for half a year, the incidence of eczema and rash of the hand, rhinitis and nasal obstruction, sore throat, headache, and nausea was significantly high in an exposed group, and the relationship with the exposure frequency was also observed (average exposure concentration: 0.01 ppm; range < 0.002 to 0.14 ppm) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (2) It was reported that, in a cross study which targeted 135 nurses in Australia who were engaged in sterilizing with 1 to 2% glutaraldehyde solutions for one year or more, the incidence of dermatitis, eyes irritation, headache, and lassitude for the past 1 year was significantly high in an exposed group (average exposure concentration: 0.032 ppm; range: 0.003 to 0.25 ppm) (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (3) It was reported that, in a study in an endoscope room in a domestic hospital, the glutaraldehyde concentration in a room without appropriate ventilation was 0.1 to 0.8 ppm, and the symptoms observed in workers were headache, eyes, nose, and throat irritation, and skin symptoms such as drying, erythema, etc. (Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (4) It was reported that, in a 4-week inhalation toxicity study with rats (6 hours/day, 5 days/week), increased relative lung weight, vacuolation of the bronchiolar epithelial cells, and fatty degeneration of the Clara cells in the bronchioles and the endothelial cells of the alveolar capillary vessel were observed at 0.000409 mg/L (converted guidance value: 0.000292 mg/L, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015)). (5) It was reported that, in a 13-week inhalation toxicity study with rats (6 hours/day, 5 days/week), lesions of the nasal cavity epithelium (squamous metaplasia of the nasal vestibule, inflammation, hyperplasia, etc. of the respiratory epithelium) were observed at 0.000512 mg/L (0.000366 mg/L, within the range for Category 1); reduced body weight gain (females) was observed at 0.00102 mg/L (0.000731 mg/L, within the range for Category 1); and wasting, dyspnea and ruffled fur, and reduced body weight gain (males) were observed at 0.00205 mg/L (0.00146 mg/L, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (6) It was reported that, in a 104-week inhalation toxicity study with rats (6 hours/day, 5 days/week), hyperplasia and inflammation of the squamous epithelium, and lower body weight (males) were observed at 0.00102 mg/L (0.000731 mg/L, within the range for Category 1); hyperplasia, inflammation, and squamous metaplasia of the respiratory epithelium, a decrease in survival (females), lower body weight, and hyaline droplet degeneration of the olfactory epithelium (females) were observed at 0.00205 mg/L (0.00146 mg/L, within the range for Category 1); and hyperplasia of the goblet cells of the respiratory epithelium, hyaline droplet degeneration of the olfactory epithelium (males), and wasting (females) were observed at 0.00307 mg/L (0.00219 mg/L, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (7) It was reported that, in a 13-week inhalation toxicity study with mice (6 hours/day, 5 days/week), dose-dependent reduced body weight gain (males), and inflammation of the nasal vestibule (females) were observed at 0.000256 mg/L (0.000183 mg/L, within the range for Category 1); squamous metaplasia, inflammation, erosion of the respiratory epithelium, and reduced body weight gain (females) were observed at 0.000512 mg/L (0.000366 mg/L, within the range for Category 1); dyspnea was observed at 0.00102 mg/L (0.000731 mg/L, within the range for Category 1); and reduced locomotor activity, tachypnea, ruffled fur, lying on belly, and squamous metaplasia and necrosis of the respiratory mucosa of the larynx were observed at 0.00205 mg/L (0.00146 mg/L, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (8) It was reported that, in a 104-week inhalation toxicity study with mice (6 hours/day, 5 days/week), hyaline droplet degeneration of the respiratory epithelium of the nasal cavity (females) was observed at 0.000256 mg/L (0.000183 mg/L, within the range for Category 1), and squamous metaplasia of the respiratory epithelium of the nasal cavity (males), lower body weight (females), and inflammation of the nasal cavity (females) were observed at 0.000512 mg/L (0.000366 mg/L, within the range for Category 1) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). [Reference Data, etc.] (9) It was reported that, in a 90-day oral toxicity study with rats dosed by drinking water, an increase in relative kidney weight, a decrease in urine volume, a decrease in water consumption (males), and increased blood urea nitrogen (females) were observed at 250 ppm (25 mg/kg/day (males), 35 mg/kg/day (females), within the range for Category 2), and decreases in food consumption, body weight gain, and water consumption (females) were observed at 1,000 ppm (100 mg/kg/day (males), 120 mg/kg/day (females), within the range for Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (10) It was reported that, in a 104-week oral toxicity study with rats dosed by drinking water, hyperplasia of the bone marrow (females) was observed at 50 ppm (4 mg/kg/day (males), 6 mg/kg/day (females), within the range for Category 1); decreased food and water consumption, reduced body weight gain, a decreasing tendency of absolute kidney weight, a decrease in urine volume and an increase in urine osmolality, and renal tubular pigmentation (females) were observed at 250 ppm (17 mg/kg/day (males), 25 mg/kg/day (females), within the range for Category 2); and gastritis, edema, and squamous epithelium hyperplasia of the forestomach, and hyperplasia of the bone marrow and renal tubular pigmentation (males) were observed at 1,000 ppm (64 mg/kg/day (males), 86 mg/kg/day (females), within the range for Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008), Risk Assessment Report (Ministry of Health, Labour and Welfare, 2015), Environmental Risk Assessment for Chemical Substances (Ministry of the Environment, 2017)). (11) It was reported that, in a 4-week dermal toxicity study with rats (6 hours/day, 5 days/week), erythema in the local site of administration, a dose-dependent increase in urea nitrogen (males), decreased water consumption (females), and increases in platelet and red blood cell count (females) were observed at 50 mg/kg/day (converted guidance value: 35.7 mg/kg/day, within the range for Category 2); reduced body weight gain (males) was observed at 100 mg/kg/day (converted guidance value: 71.4 mg/kg/day, within the range for Category 2); and edema in the local site of administration (males), and an increase in relative adrenal gland weight (females) were observed at 150 mg/kg/day (converted guidance value: 107 mg/kg/day, within the range for Category 2) (Initial Risk Assessment Report (NITE, CERI, NEDO, 2008)). |
| 10 | Aspiration hazard | Classification not possible |
- |
- | - | [Rationale for the Classification] 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 Short term (Acute) | Category 1 |
 Warning |
H400 | P273 P391 P501 |
It was classified in Category 1 from 48-hour LC50 = 0.07 mg/L for crustacea (Acartia tonsa) (EU CLP CLH, 2013). |
| 11 | Hazardous to the aquatic environment Long term (Chronic) | Category 2 |
- |
H411 | P273 P391 P501 |
It was classified in Category 2 because it was rapidly degradable (a 28-day degradation rate by BOD: 59%, a 28-day degradation rate by TOC: 86%, a 28-day degradation rate by GC: 100% (Biodegradation and Bioconcentration Results of Existing Chemical Substances under the Chemical Substances Control Law, METI, 1995)), and due to 72-hour NOErC = 0.025 mg/L for algae (Desmodesmus subspicatus) (EU CLP CLH, 2013). The classification result was revised from the previous classification by changing how to classify it in chronic toxicity and using new information. |
| 12 | Hazardous to the ozone layer | Classification not possible |
- |
- | - | This substance is not listed in the Annexes to the Montreal Protocol. |
NOTE:
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