NITE - Chemical Management Field

GHS Classification Results by the Japanese Government

GENERAL INFORMATION

Item	Information
CAS RN	55406-53-6
Chemical Name	3-iodo-2-propynyl butylcarbamate
Substance ID	R02-A-023-METI, MOE
Classification year (FY)	FY2020
Ministry who conducted the classification	Ministry of Economy, Trade and Industry (METI)/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 (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)
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	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (acetylenes) present in the molecule, but the classification is not possible due to no data.
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	Classification not possible	- -	-	-	No data available. Besides, there is information that it is combustible (GESTIS (accessed Aug. 2020)).
8	Self-reactive substances and mixtures	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (acetylenes) present in the molecule, but the classification is not possible due to no data.
9	Pyrophoric liquids	Not classified (Not applicable)	- -	-	-	Solid (GHS definition)
10	Pyrophoric solids	Classification not possible	- -	-	-	No data available.
11	Self-heating substances and mixtures	Classification not possible	- -	-	-	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	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)	- -	-	-	Solid (GHS definition)
14	Oxidizing solids	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.
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	- -	-	-	Classification is not possible because test methods applicable to solid substances are not available.
17	Desensitized explosives	Classification not possible	- -	-	-	There is a chemical group associated with explosive properties (acetylenes) present in the molecule, but the classification is not possible due to no data.

HEALTH HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
1	Acute toxicity (Oral)	Category 4	Warning	H302	P301+P312 P264 P270 P330 P501	[Rationale for the Classification] It was classified in Category 4 from (1) - (5). [Evidence Data] (1) LD50 for rats (males): 1,100 mg/kg (AICIS (formerly, NICNAS IMAP) (2013)) (2) LD50 for rats (females): 1,795 mg/kg (AICIS (formerly, NICNAS IMAP) (2013)) (3) LD50 for rats (females): 1,100 mg/kg (EPA Pesticide RED (1997)) (4) LD50 for rats: 1,500 mg/kg (EPA Pesticide RED (1997)) (5) LD50 for rats: between 300-2,000 mg/kg (OECD TG 423) (CLH Report (2017))
1	Acute toxicity (Dermal)	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) LD50 for rats: > 2,000 mg/kg (OECD TG 402) (CLH Report (2017)) (2) LD50 for rabbits: > 2,000 mg/kg (EPA Pesticide RED (1997), AICIS (formerly, NICNAS IMAP) (2013))
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 3	Danger	H331	P304+P340 P403+P233 P261 P271 P311 P321 P405 P501	[Rationale for the Classification] It was classified in Category 3 from (1) - (6). Besides, (7) was not used for classification because it is mentioned in the EU CLH report (2011) that no particle size distribution was measured in the test, and it contained much of not-respirable dust. [Evidence Data] (1) LC50 for rats (4 hours): 0.68 mg/L (dust) (AICIS (formerly, NICNAS IMAP) (2013)) (2) LC50 for rats (4 hours): 0.78 mg/L (mist) (AICIS (formerly, NICNAS IMAP) (2013)) (3) LC50 for rats (4 hours): 0.67 mg/L (dust) (EU CLH report (2011), EPA Pesticide RED (1997)) (4) LC50 for rats (males) (4 hours): 0.63 mg/L (mist) (EU CLH report (2011), EPA Pesticide RED (1997)) (5) LC50 for rats (females) (4 hours): 0.99 mg/L (mist) (EU CLH report (2011), EPA Pesticide RED (1997)) (6) LC50 for rats (4 hours): 0.67 mg/L (micronized and non-micronized dust), 0.88 mg/L (non-micronized dust) (EU CLH report (2011)) [Reference Data, etc.] (7) LC50 for rats (4 hours): > 6.89 mg/L (dust) (EU CLH report (2011), REACH registration dossier (Accessed Aug. 2020))
2	Skin corrosion/irritation	Not classified	- -	-	-	[Rationale for the Classification] It was classified as "Not classified" from (1), (2). [Evidence Data] (1) It is reported that in a skin irritation test with rabbits (n = 6) (GLP, semi-occlusive, 4-hour application, 72-hour observation), slight or moderate erythema and slight edema were observed in the animals after 24 hours, one of which continued to have slight erythema by 72 hours (erythema/eschar score: 0/0/1.3/0.3/0/0, edema score: 0.3/0/0/0/0/0.6) (REACH registration dossier (Accessed Aug. 2020)). (2) It is reported that in a skin irritation test with rabbits (n = 6) (GLP, semi-occlusive, 4-hour application, 9-day observation), primary dermal irritation index (PDII) was 2.63, the mean score after 24/48/72 hours was 1.44 for erythema and 1.06 for edema, and effects fully disappeared within 4 days (REACH registration dossier (Accessed Aug. 2020)). [Reference Data, etc.] (3) It is reported that in a clinical test in which 0.1% and 0.5% mixtures (petrolatum) of this substance were used, slight skin irritation was shown, but no skin sensitization was seen (AICIS (formerly, NICNAS IMAP) (2013)). (4) It is reported that in a primary skin irritation test by 24-hour occlusive application of a cosmetic containing 0.0125% of this substance, a slight irritation change (erythema only) was found (AICIS (formerly, NICNAS IMAP) (2013)).
3	Serious eye damage/eye irritation	Category 1	Danger	H318	P305+P351+P338 P280 P310	[Rationale for the Classification] It was classified in Category 1 from (1) - (4). [Evidence Data] (1) It is reported that in an eye irritation test with rabbits (n = 9) (GLP, 21-day observation), corneal injury (corneal epithelial sloughing) in 6 animals in the non-rinsed group, corneal opacity and conjunctival irritation did not fully disappear within 21 days (corneal opacity score: 2.7/2.7/2.7/2/2.7/2.7, iritis score: 1.3/1/1.3/1/1/1, conjunctival redness score: 2/2/2/2/2.3/2, chemosis score: 3/3/3/3/3/3) (REACH registration dossier (Accessed Aug. 2020)). (2) It is reported that in an eye irritation test with rabbits (n = 6) (GLP, 14-day observation), all the animals showed corneal opacity and moderate to severe conjunctival irritation, which persisted for 14 days (It was not possible to determine some of the scores for corneal opacity, iritis, and conjunctival redness due to the mean chemosis score of 4 after 24/48/72 hours) (REACH registration dossier (Accessed Aug. 2020)). (3) It is reported that in an eye irritation test with rabbits, the mean score after 24/48/72 hours was 1.67 for chemosis, 1.17 for iritis, 2.17 for conjunctival redness, and 4 for chemosis, and there was no full recovery after 7 days (CLH Report (2011)). (4) It is reported that a marketed product of this substance (technical grade) was severely irritating to the rabbit eye, and corneal opacity and corneal vascularization were observed in the unwashed eye group by 21 days (AICIS (formerly, NICNAS IMAP) (2013)).
4	Respiratory sensitization	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.
4	Skin sensitization	Category 1A	Warning	H317	P302+P352 P333+P313 P362+P364 P261 P272 P280 P321 P501	[Rationale for the Classification] It was classified in Category 1A from (1) - (5). [Evidence Data] (1) It is reported that in a patch test in 23 metalworkers (a variety of metalworking fluids containing 0.5-2.5% of this substance), positive reactions were seen in 5 (EU CLH report (2011), AICIS (formerly, NICNAS IMAP) (2013)). (2) It is reported that in a patch test in 26,335 persons (0.2% solution (petrolatum)), a sensitization rate was 0.8% (DFG MAK (2016)). (3) Other than (1) (2), reports from multiple epidemiological surveys showed positive reactions at relatively high incidences (CLH Report (2011), HSDB (Accessed Aug. 2020), AICIS (formerly, NICNAS IMAP) (2013), DFG MAK (2016)). (4) It is reported that in a maximization test with guinea pigs (n = 10) (OECD TG 406, GLP, intradermal administration: 1% solution), a positive rate was 80% (8/10), 90% (9/10) at 48, 72 hours after challenge (CLH Report (2011), AICIS (formerly, NICNAS IMAP) (2013), REACH registration dossier (Accessed Aug. 2020)). (5) It is reported that in a local lymph node assay (LLNA) with mice (OECD TG 429), the EC3 was calculated as 0.87% (AICIS (formerly, NICNAS IMAP) (2013), REACH registration dossier (Accessed Aug. 2020)).
5	Germ cell mutagenicity	Not classified	- -	-	-	[Rationale for the Classification] Based on (1) to (4), it was classified as "Not classified." [Evidence Data] (1) In two micronucleus tests with mice (chromosomal aberration in peripheral blood erythrocytes: intraperitoneal injection and oral gavage administration), negative results were reported (CLH Report (2011)). (2) In a bacterial reverse mutation test (OECD TG471), negative results were reported (CLH Report (2011)). (3) In an in vitro mammalian cell gene mutation test (OECD TG 476), negative results were reported (CLH Report (2011)). (4) In an in vitro mammalian chromosomal aberration test (OECD TG473), negative results (+S9) or equivocal results (-S9) were reported, and in UDS assays in primary rat hepatocytes, negative results were reported (CLH Report (2011), AICIS (previous NICNAS IMAP) (2013))
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, EPA classified the substance as NL (Not Likely to be Carcinogenic to Humans) (EPA Annual Cancer Report 2018 (Accessed on July 2020): Classification in 1996). (2) In a two-year combined chronic toxicity/carcinogenicity study with rats by feeding, no evidence of carcinogenicity was observed at doses of up to 80 mg/kg/day (CLH Report (2011), AICIS (previous NICNAS IMAP) (2013)). (3) In a 78-week carcinogenicity study with mice dosed by feeding, an increase in the incidence of hepatocellular adenomas (11/50) was observed in males at the highest dose of 150 mg/kg/day (CLH Report (2011), AICIS (previous NICNAS IMAP) (2013)). [Reference Data, etc.] (4) EPA re-evaluated liver tumors in mice and found that there was no increase in the incidence of combined hepatocellular adenoma/carcinoma of the liver in male mice and no carcinogenic response in female mice and in male or female rats, and this substance was not a mutagen. Therefore, EPA concluded that this substance was not likely to be carcinogenic in humans and was evaluated in (1) (EPA Pesticide RED (1997), RAC Opinion (2012)). (5) Concerning liver tumors in mice, EU presented the view that the strain of mice (CD-1) used in the test was a strain in which spontaneous neoplasm occurred most frequently (control group male: 4/50, historical control: 1 to 8/50 cases (2 to 18%)) and that the tumors observed in the liver were only benign tumors, therefore, extrapolation of the findings to carcinogenicity evaluation in humans was not considered to be of biological relevance, and EU concluded that no category was assigned (ECHA RAC Opinion (2012), CLH Report (2011), AISIS (previous NICNAS IMAP) (2013)).
7	Reproductive toxicity	Not classified	- -	-	-	[Rationale for the Classification] In (1), the effects such as a decrease in survival index was observed in the offspring at doses where no severe maternal toxicity was observed, but the RAC judged that classification for reproductive toxicity was not necessary because the effects resulted from maternal toxicity and no similar effects were observed in F2 offspring. In (2), minor developmental toxicity effects were observed in the offspring, while in (3), no developmental toxicity effects were observed. With all the above findings considered, it was not possible to judge clearly whether the effects observed in the offspring resulted from severe maternal toxicity, therefore, classification was not possible. [Evidence Data] (1) It was reported that in a two-generation reproduction toxicity study with rats dosed by gavage (OECD TG416, for 10 weeks prior to mating (F0), for 13 weeks prior to mating (F1)), at 30 mg/kg/day, general toxicity effects (salivation, bent posture and paddling with the front paws (F0 and F1 males and females)) and one case of dystocia were observed in parental animals, and decreases in survival index and cumulative survival index in F1 offspring and a decrease in body weight in F2 offspring (females) on day 21 after birth were observed. The RAC judged that the effects such as a decrease in survival index observed in offspring at 100 mg/kg/day resulted from maternal toxicity and as for decreases in survival index and cumulative survival index observed in F1 offspring at 30 mg/kg/day, no similar effects were observed in F2 offspring, therefore, classification for reproductive toxicity was not necessary (ECHA RAC Opinion (2012), AICIS (previous NICNAS IMAP) (2013), DFG MAK (2016)). (2) It was reported that in a developmental toxicity study with rats dosed by gavage (OECD TG 414, gestation days 6 to 15), at 75 mg/kg/day, salivation, and aggressive behavior was observed and at 250 mg/kg/day, reduced body weight gain, decreased feed consumption, and increases in absolute and relative liver weight were observed in parental animals, while lower body weight of fetuses (females), minor rib defects, incomplete ossification or non-ossification, and incomplete ossification of 5th sternebrae (retarded ossifications were secondary effects of maternal toxicity) were observed in offspring (ECHA RAC Opinion (2012), AICIS (previous NICNAS IMAP) (2013), EPA Pesticide RED (1997), DFG MAK (2016)). (3) It was reported that in a developmental toxicity study with rabbits dosed by gavage (OECD TG414, gestational days 6 to 15), no developmental toxicity was observed (ECHA RAC Opinion (2012), DFG MAK (2016)). [Reference Data, etc.] (4) It was reported that in a two-generation reproduction toxicity study with rats dosed by feeding (for 14 weeks prior to mating (F0), for 13 weeks prior to mating (F1)), no reproductive toxicity was observed. In this test, the stability of this substance in the feed was not fully confirmed. Therefore, it was judged inadequate for the evaluation of reproductive toxicity (AICIS (previous NICNAS IMAP) (2013)).
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), respiratory symptoms were observed, and although the doses at which the symptoms appeared were not clear, it was considered from the LC50 value that the symptoms were effects within Category 1. Therefore, this substance was classified in Category 1 (respiratory organs). It was not possible to identify target organs from the data of (2) to (5) in the oral and dermal routes. [Evidence Data] (1) In an acute inhalation exposure test with rats, the rats showed a decrease in spontaneous activity, eye closure, and excessive lacrimation. Labored breathing, gasping and an increase in secretory discharges were observed in the survivors within one week after the exposure, and at necropsy, pulmonary edema, emphysema and reddened lungs were observed in the rats that died. It was reported that the LC50 in dust exposure was approx. 0.67 mg/L and that in liquid aerosol exposure was approx. 0.78 mg/L (AICIS (previous NICNAS IMAP) (2013)). [Reference Data, etc.] (2) It was reported that in an acute oral toxicity test with rats, soft feces, urine stains, rough coats, slight depression, and red stains on the eye and nose areas were observed at 1000-1500 mg/kg (within the range for Category 2) (AICIS (previous NICNAS IMAP) (2013)). (3) In an acute oral toxicity test with rats, decreased spontaneous motility, piloerection, pallor, and labored breathing were observed at 300 mg/kg (within the range for Category 1). It was reported that the LD50 value was between 300 mg/kg and 500 mg/kg (EU CLH Report (2011)). (4) It was reported that in an acute dermal toxicity test with rats, redness, formation of scale, and encrustation in treated skin areas were observed at 2,000 mg/kg (within the range for Category 2) (EU CLH Report (2011)). (5) It was reported that in an acute dermal toxicity test with rabbits, erythema and edema occurred at the areas treated at 2,000 mg/kg (within the range for Category 2) (AICIS (previous NICNAS IMAP) (2013)).
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), histopathological alterations in the larynx were observed in the inhalation route and it was classified in Category 1 (respiratory organs). In addition, based on (2) to (5), it was classified as "Not classified" in the oral and dermal routes. [Evidence Data] (1) In a 13-week inhalation exposure test with rats (6 hours/day, 5 days/week), histopathological alterations in the larynx (necrosis in the ventral cartilage, epithelial hyperplasia in ventral region, and hyperplasia and squamous metaplasia in dorsoventral region) were observed at 6.7 mg/m3 (converted guidance value: 0.0048 mg/L, within the range for Category 1). It was reported that although reduced plasma, erythrocyte, and brain ChE activities were observed in males and/or females in the same dose group, due to no clear dose-relationship observed, it was considered that the findings were of unclear relevance to effects (AICIS (previous NICNAS IMAP) (2013) & EU CLH Report (2011), REACH registration dossier (Accessed Aug. 2020)). (2) It was reported that in a 13-week oral toxicity test with rats dosed by gavage, salivation, lethargy, wheezing, and epistaxis were noted in males at and above 50 mg/kg/day (within the range for Category 2) and in females at 125 mg/kg/day (in the range corresponding to “Not classified”) (AICIS (previous NICNAS IMAP) (2013)). (3) It was reported that in a two-year combined chronic toxicity/carcinogenicity study with rats by feeding, histopathological alterations in the stomach (such as submucosal edema, submucosal inflammation, acanthosis, hyperkeratosis, ulceration, and basal membrane proliferation) were observed at the highest dose of 80 mg/kg/day (within the range for Category 2), but no other specific organ toxicity was observed (AICIS (previous NICNAS IMAP) (2013)). (4) In a 78-week carcinogenicity study with mice dosed by feeding, effects on the thyroids (enlarged thyroids accompanied by foci of small vacuolated cells most likely of follicular cell origin and general follicular enlargement) were observed at 150 mg/kg/day (in the range corresponding to “Not classified”), but the toxicological significance of these findings was unclear. It was also reported that no adverse effects were observed (AICIS (previous NICNAS IMAP) (2013)). (5) It was also reported that in a 91-day dermal toxicity test with rats (6 hours/day, 5 days/week), skin irritation effects (acanthosis and hyperkeratosis) were observed but no systemic toxicity effects were observed at the highest dose of 500 mg/kg/day (357 mg/kg/day, in the range corresponding to “Not classified”) (EU CLH Report (2011), AICIS (previous NICNAS IMAP) (2013)).
10	Aspiration hazard	Classification not possible	- -	-	-	[Rationale for the Classification] Classification not possible due to lack of data.

ENVIRONMENTAL HAZARDS

Hazard class		Classification	Pictogram Signal word	Hazard statement (code)	Precautionary statement (code)	Rationale for the classification
11	Hazardous to the aquatic environment Short term (Acute)	Category 1	Warning	H400	P273 P391 P501	It was classified in Category 1 from 72-hour EC50 = 0.053 mg/L for algae (Desmodesmus subspicatus) (REACH registration dossier, 2021).
11	Hazardous to the aquatic environment Long term (Chronic)	Category 1	Warning	H410	P273 P391 P501	It was classified in Category 1 because it was not rapidly degradable (not readily degradable, a degradation rate by carbon dioxide evolution: 0% (EU RAC (Background Document), 2012)) and due to 72-hour NOEC = 0.0046 mg/L for algae (Desmodesmus subspicatus) (REACH registration dossier, 2021).
12	Hazardous to the ozone layer	Classification not possible	- -	-	-	This substance is not listed in the Annexes to the Montreal Protocol.

NOTE:

GHS Classification Result by the Japanese Government is intended to provide a reference for preparing a GHS label or SDS for users. To include the same classification result in a label or SDS for Japan is NOT mandatory.
Users can cite or copy this classification result when preparing a GHS label or SDS. Please be aware, however, that the responsibility for a label or SDS prepared by citing or copying this classification result lies with users.
This GHS classification was conducted based on the information sources and the guidance for classification and judgement which are described in the GHS Classification Guidance for the Japanese Government etc. Using other literature, test results etc. as evidence and including different content from this classification result in a label or SDS are allowed.
Hazard statement and precautionary statement will show by hovering the mouse cursor over a code in the column of "Hazard statement" and "Precautionary statement," respectively. In the excel file, both the codes and statements are provided.
A blank or "-" in the column of "Classification" denotes that a classification for the hazard class was not conducted in the year.
An asterisk “*” in the column of “Classification” denotes that “Not classified (or No applicable)” and/or “Classification not possible” is applicable. Details are described in the column of “Rationale for the classification”. If no English translation is available for “Rationale for the classification,” please refer to the Japanese version of the results.

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