NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	643-79-8
Chemical Name	Phthalaldehyde
Substance ID	R01-A-012
Classification year (FY)	FY2019
Ministry who conducted the classification	Ministry of Health, Labour and Welfare (MHLW)/Ministry of the Environment (MOE)
New/Revised	New
Classification result in other fiscal year
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)
Model SDS by MHLW (External link)
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	*	- -	-	-	No data available.
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	*	- -	-	-	No data available.
11	Self-heating substances and mixtures	*	- -	-	-	Classification is not possible because test methods applicable to solid (melting point <= 140 deg C) substances are not available.
12	Substances and mixtures which, in contact with water, emit flammable gases	*	- -	-	-	The chemical structure of the substance does not contain metals or metalloids (B, Si, P, Ge, As, Se, Sn, Sb, Te, Bi, Po, At). It was classified as "Not classified (Not applicable)."
13	Oxidizing liquids	*	- -	-	-	Solid (GHS definition). It was classified as "Not classified (Not applicable)."
14	Oxidizing solids	*	- -	-	-	The substance is an organic compound containing oxygen (but not fluorine or chlorine) which is chemically bonded only to carbon or hydrogen. It was classified as "Not classified (Not applicable)."
15	Organic peroxides	*	- -	-	-	Organic compounds containing no bivalent -O-O- structure in the molecule. 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)	Category 3	Danger	H301	P301+P310 P264 P270 P321 P330 P405 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 3. [Evidence Data] (1) LD50 for rats: 121 mg/kg (ACGIH (7th, 2019)) (2) LD50 for rats: 178.46 mg/kg (REACH registration dossier (Access on August 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 (REACH registration dossier (Access on August 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] Classification not possible due to lack of data.
2	Skin corrosion/irritation	Category 1	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), it was classified in Category 1. [Evidence Data] (1) In a skin irritation test (4 hour-semi-occlusive application) with rabbits in compliance with OECD TG 404, the mean scores for erythema and edema at 24/48/72 hours were 1.8 and 2.9, respectively. Since eschar and scars were notable 14 days post application, it was judged to be corrosive (REACH registration dossier (Access on July 2019)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] Because it was judged as Skin corrosion (Category 1) based on (1), it was classified in Category 1. [Evidence Data] (1) In a skin irritation test (4 hour-semi-occlusive application) with rabbits in compliance with OECD TG 404, the mean scores for erythema and edema at 24/48/72 hours were 1.8 and 2.9, respectively. Since eschar and scars were notable 14 days post application, it was judged as Skin corrosion (Category 1) (REACH registration dossier (Access on July 2019)).
4	Respiratory sensitization	Category 1	Danger	H334	P304+P340 P342+P311 P261 P284 P501	[Rationale for the Classification] Based on (1)-(2), it was classified in Category 1. [Evidence Data] (1) Multiple cases of bronchial asthma and contact dermatitis associated with occupational exposures to this substance were reported (NTP TOX84 (2018)). (2) In a study investigating adverse health effects in 70 workers in hospital endoscopy units using this substance, 17 workers were diagnosed with contact dermatitis, occupational asthma, or eye irritation (NTP TOX84 (2018)).
4	Skin sensitization	Category 1A	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] The mouse strain used in (1) was not a recommended one in OECD TG 429, but the EC3 was reported to be 0.051%, equivalent to Category 1A, and the result in (2) also supported Category 1A. Therefore, it was classified in Category 1A. [Evidence Data] (1) The EC3 was reported to be 0.051% in a mouse local lymph node assay (LLNA) with BALB/c mice (ACGIH (7th, 2019)). (2) In a maximization test (according to OECD TG 406 and GLP, intradermal induction 0.1%, epicutaneous induction 1%, challenge 0.1%) with guinea pigs (20 females), positive reactions were observed in 19/20 animals (REACH registration dossier (Access on July 2019)).
5	Germ cell mutagenicity	*	- -	-	-	[Rationale for the Classification] Based on (1) and (2), there were insufficient data to conclude that there was no concern about genotoxicity. Therefore, classification was not possible due to lack of data. [Evidence Data] (1) As for in vivo, there were reports of a negative result in a micronucleus test (3-month inhalation exposure) with rats and negative or equivocal results in micronucleus tests (3-month inhalation exposure) with mice (NTP DB (Access on June 2019), NTP TOX84 (2018)). (2) As for in vitro, there was a report of a positive result in a bacterial reverse mutation test (NTP DB (Access on June 2019), NTP TOX84 (2018)).
6	Carcinogenicity	*	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
7	Reproductive toxicity	*	- -	-	-	[Rationale for the Classification] Based on (1), as for developmental toxicity, no effects on embryo/fetuses were observed even at doses where maternal toxicity was observed. However, since there were no data on fertility, it was classified as "Classification not possible" due to lack of data. [Evidence Data] (1) In a developmental toxicity test (according to EPA OPP 83-3) in which female rats were dosed orally on gestational days 6-15, only lower body weight and skeletal variations were observed in fetuses even at medium and high doses where deaths occurred in maternal animals (RREACH registration dossier (Access on July 2019)). [Reference Data, etc.] (2) In 14-week repeated-dose toxicity tests with rats and mice via the inhalation route, decreased weights of the testis, epididymis and cauda epididymis were observed in rats, and in rats and mice decreased sperm motility, and histopathologic lesions of the testis and epididymis (increased exfoliated germ cells in the epididymis, spermatid degeneration in the testis, apoptosis of the germinal epithelium and interstitial cell atrophy, etc.) were observed (NTP TOX84 (2018)). (3) No evidence of abortion or birth defects were noted in experimental animals exposed to phthalaldehyde during pregnancy, but delayed bone development was observed at high doses where maternal toxicity was observed. Data on the potential for phthalaldehyde to cause infertility in experimental animals were not available. However, damage to the testis and reduced sperm counts and motility were observed in male animals following repeated exposure to low concentrations of phthalaldehyde (HSDB (Access on June 2019)). These were used as reference data since they were that of a mixture, and the details are unknown.
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] Because it is reported that it affected the respiratory organs in humans in (1)-(3), it was classified in Category 1 (respiratory organs). [Evidence Data] (1) Many accidental exposure cases in patients due to the use of medical equipment (transesophageal electroradiography probes and colonoscopes, etc.) that was sterilized with this substance and inadequately rinsed were reported (NTP TOX84 (2018)). One case in which a patient suffered burns to the lips, tongue, larynx and esophagus was described in the original source article (Venticinque et al., Anesth. Analg. 97, 1260-1261, 2003). (2) There is a case report of a patient who suffered burns in the oropharynx and larynx because an endoscope used was inadequately washed, and this substance used as a disinfectant remained and adhered to it (HSDB (Access on June 2019)). (3) There is a case report of a patient who developed widespread/severe skin and mucous membrane damage of the lips, tongue, pharynx and esophagus areas due to the use of transesophageal echo devices where this substance remained or adhered due to inadequate washing after the sterilization with it (HSDB (Access on June 2019)).
9	Specific target organ toxicity - Repeated exposure	Category 1 (respiratory organs, reproductive organs (male))	Danger	H372	P260 P264 P270 P314 P501	[Rationale for the Classification] Based on (1) and (2), it was classified in Category 1 (respiratory organs, reproductive organs (men)). [Evidence Data] (1) As a result of a 14-week inhalation exposure test (6 hours/day, 5 days/week) with rats at concentrations of 0.44-7.0 ppm (converted guidance value: 0.002-0.03 mg/L, within the range of Category 1), suppurative inflammation of the nasal cavity at or above 0.44 ppm, abnormal breathing, sneezing, decreased testes weights, effects on the nasal cavity, larynx and trachea, etc. at or above 0.88 ppm, and deaths, effects on the alveolus and bronchus, atrophy of the interstitial cells in the testis, etc. at or above 3.5 ppm were observed, and all animals died at 7.0 ppm (NTP TOX84 (2018)). (2) As a result of a 14-week inhalation exposure test (6 hours/day, 5 days/week) with mice at concentrations of 0.44-7.0 ppm (converted guidance value: 0.002-0.03 mg/L, within the range of Category 1), suppurative inflammation of the nasal cavity and decreased sperm motility, etc. at or above 0.44 ppm, decreased hemoglobin and hematocrit values, and effects on the nasal cavity, etc. at or above 0.88 ppm, decreased erythrocyte counts and chronic active inflammation of the larynx, etc. at or above 1.75 ppm, and deaths, abnormal breathing, effects on the trachea, bronchioli of the lungs and bone marrow hyperplasia (increased myeloblast/erythroblast ratio), etc. at or above 3.5 ppm were observed, and all animals died at 7.0 ppm. Among these results, the effects on the blood system and bone marrow were considered to be changes associated with inflammation of the respiratory organs, etc. (NTP TOX84 (2018)).
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)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 96-hour EC50 = 0.184 mg/L for algae (Pseudokirchneriella subcapitata) (U.S.EPA: OPP Pesticide Ecotoxicity Database, 2019).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	Reliable chronic toxicity data were not obtained. It was classified in Category 1 because sufficient data on rapid degradability were not obtained, and it was classified in Category 1 in acute toxicity.
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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