GHS Classification Result (Revision of the past classification result)

Chemical Name:Toxaphene
CAS:8001-35-2

Result:
ID: 22B4501
Classifier: Ministry of Health, Labour and Welfare (MHLW), Ministry of the Environment (MOE)
Year Classified: FY2010
Reference Manual: GHS Classification Guidance by the Japanese Government (July, 2010)

PHYSICAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Explosives Not applicable - - - - There are no chemical groups associated with explosive properties present in the molecule.
2 Flammable gases (including chemically unstable gases) Not applicable - - - - Solid (GHS definition)
3 Aerosols Not applicable - - - - Not aerosol products.
4 Oxidizing gases Not applicable - - - - Solid (GHS definition)
5 Gases under pressure Not applicable - - - - Solid (GHS definition)
6 Flammable liquids Not applicable - - - - Solid (GHS definition)
7 Flammable solids Not classified - - - - Not combustible (HSDB (2005))
8 Self-reactive substances and mixtures Not applicable - - - - There are no chemical groups present in the molecule associated with explosive or self-reactive properties.
9 Pyrophoric liquids Not applicable - - - - Solid (GHS definition)
10 Pyrophoric solids Not classified - - - - Not combustible (HSDB (2005))
11 Self-heating substances and mixtures Not classified - - - - Not combustible (HSDB (2005))
12 Substances and mixtures which, in contact with water, emit flammable gases 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 applicable - - - - Solid (GHS definition)
14 Oxidizing solids Not applicable - - - - The substance is an organic compound containing chlorine (but not oxygen or fluorine) in the molecule, which is chemically bonded only to carbon.
15 Organic peroxides Not applicable - - - - Organic compounds containing no bivalent -O-O- structure
16 Corrosive to metals Classification not possible - - - - Test methods applicable to solid substances are not available.

HEALTH HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
1 Acute toxicity (Oral) Category 3 Danger H301: Toxic if swallowed P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment (see ... on this label).
P330: Rinse mouth.
P405: Store locked up.
P501: Dispose of contents/container to ...
Seven LD50 values for rats of 80, 90, 80 mg/kg (ATSDR (1996)), 293, 220 mg/kg (IARC 79 (2001)), 60 and 120 mg/kg (EHC 45 (1984)) were reported, and all of them corresponded to Category 3.
1 Acute toxicity (Dermal) Category 3 Danger H311: Toxic in contact with skin P302+P352: IF ON SKIN: Wash with plenty of soap and water.
P280: Wear protective gloves/protective clothing/eye protection/face protection.
P312: Call a POISON CENTER or doctor/physician if you feel unwell.
P322: Specific treatment (see ... on this label).
P361: Remove/Take off immediately all contaminated clothing.
P363: Wash contaminated clothing before reuse.
P405: Store locked up.
P501: Dispose of contents/container to ...
As for rats, the LD50 value of 1075 mg/kg (male) and 780 mg/kg (female) were reported (ATSDR (1996)). Therefore, Category 3 was adopted taking the greater hazard. As for rabbits, based on the LD50 value of 1025 - 1075 mg/kg (EHC 45 (1984)), Category 4 was adopted. Selecting the category derived from the rat data with greater hazard, the substance was classified as Category 3.
1 Acute toxicity (Inhalation: Gases) Not applicable - - - - Solid (GHS definition)
1 Acute toxicity (Inhalation: Vapours) Classification not possible - - - - No data available.
1 Acute toxicity (Inhalation: Dusts and mists) Category 3 Danger H331: Toxic if inhaled P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
P403+P233: Store in a well-ventilated place. Keep container tightly closed.
P261: Avoid breathing dust/fume/gas/mist/vapours/spray.
P271: Use only outdoors or in a well-ventilated area.
P311: Call a POISON CENTER or doctor/physician.
P321: Specific treatment (see ... on this label).
P405: Store locked up.
Based on the rat LC50 value (dust) of 3.4 mg/L/1hr = 0.85 mg/L/4hrs (ATSDR (1996)), the substance was classified as Category 3. It was described in the source document that the test condition was dust (ATSDR (1996)).
2 Skin corrosion/irritation Not classified - - - - In the 4-hour rabbit test, application of 500 mg of the substance caused only mild irritation (ATSDR (1996)). And in human cases, acute exposure of the substance did not cause irritation. Based on these documents, the substance was classified as "Not classified" in the JIS classification (corresponding to Category 3 in the UN-GHS classification). As relevant information, the substance was classified as "Xi; R37/38" in the EU classification (EU-Annex 1 (Access on May 2009)).
3 Serious eye damage/eye irritation Classification not possible - - - - Insufficient data were available. As relevant information, mild irritation of the eyelids was observed after 14 times applications to the eyes of guinea pigs, and eyes were not affected (ATSDR (1996)). However, it is the only summary of an unpublished report, and it was described that the validity of the examination containing protocol and data could not be evaluated (ATSDR (1996)). Therefore, the data were not adopted for the basis for classification.
4 Respiratory sensitization Classification not possible - - - - No data available.
4 Skin sensitization Classification not possible - - - - No data available.
5 Germ cell mutagenicity Not classified - - - - The substance was classified as "Not classified" based on the negative results in the dominant lethal test using mice orally or intraperitoneally administered (in vivo inheritable mutagenicity test in germ cells) (DFGMAK-Doc. 19 (2003)). As relevant information for the human case, the incidence of chromosomal aberration in peripheral blood lymphocytes of eight women who were working in the area where this substance was sprayed by airplane was 13.1% in comparison with 1.6% of the control group (IARC 79 (2001)). However, it was unclear whether the cause of these cases depended on the direct effects of this substance (ATSDR (1996)). As for in vitro studies, positive results in the Ames test and negative results in the HPRT test using Chinese hamster V79 cells were reported (IARC 79 (2001)).
6 Carcinogenicity Category 2 Warning H351: Suspected of causing cancer P308+P313: IF exposed or concerned: Get medical advice/attention.
P201: Obtain special instructions before use.
P202: Do not handle until all safety precautions have been read and understood.
P281: Use personal protective equipment as required.
P405: Store locked up.
P501: Dispose of contents/container to ...
The substance was classified as Category 2 based on the carcinogenicity criteria of "Group 2B" in the IARC (IARC 79 (2001)), "A3" in the ACGIH (ACGIH (2001)), and "Category 3" in the EU (EU-Annex 1 (Access on May 2009)). As relevant information, in the 80-week dietary tests using rats and mice, the increases in the incidences of thyroid tumors in rats and hepatocellular carcinomas in mice were reported (NTP TR37 (1979)).
7 Reproductive toxicity Not classified - - - - In the three-generation study (EHC 45 (1984)) or two-generation study (DFGMAK-Doc.19 (2003)) by oral administration in rats, no effects on sexual functions, reproductive performance, fertility, and lactation were observed at the dose levels that cause general toxicity in parental animals. In addition, five generation study by oral administration in mice (IARC 79 (2001)), no embryotoxic or teratogenic effects were observed. Furthermore, in the oral administration studies using rats or mice during the organogenetic period, increase in the incidence of extra ribs in rats, and increase in the incidence of encephalocele in mice were reported (IARC 79 (2001)). However, since these effects were observed only at the high dose level that maternal deaths were produced, the observation of the study was not adopted as the basis for classification. In these studies administered during the organogenetic period, other effects containing teratogenicity were not reported (IARC 79 (2001)). Therefore, since in these multi generation studies and developmental toxicity studies in rats or mice, no adverse effects were observed, the substance was classified as "Not classified".
8 Specific target organ toxicity - Single exposure Category 1 (central nervous system) Danger H370: Causes damage to organs (central nervous system) P307+P311: IF exposed: Call a POISON CENTER or doctor/physician.
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P321: Specific treatment (see ... on this label).
P405: Store locked up.
P501: Dispose of contents/container to ...
As the acute poisoning symptoms after ingestion of the substance in humans, clinical signs such as involuntary jerking movements of the extremities, muscle spasms, nausea and vomiting appeared (DFGMAK-Doc. 19 (2003)), and convulsions occurred in all patients, regardless of survival or death (ACGIH (2001), DFGMAK-Doc. 19 (2003)). Moreover, there was a description stating that the substance induced general stimulation of the central nervous system (ACGIH (2001)). Furthermore, it was also reported that signs such as clonic-tonic convulsions, salivation, vomiting and hyperreflexia, etc. were observed in the acute inhalation study in mice exposed at 20 mg/m3 over 2 hours (converted value as that of 4h-exposure: 0.01 mg/L) (ACGIH (2001)). Based on the above findings, the substance was classified as Category 1 (central nervous system).
9 Specific target organ toxicity - Repeated exposure Category 1 (liver, kidney, thyroid), Category 2 (central nervous system) Danger
Warning
H372: Cause damage to organs through prolonged or repeated exposure (liver, kidney, thyroid)
H373: May cause damage to organs through prolonged or repeated exposure (central nervous system)
P260: Do not breathe dust/fume/gas/mist/vapours/spray.
P264: Wash ... thoroughly after handling.
P270: Do not eat, drink or smoke when using this product.
P314: Get medical advice/attention if you feel unwell.
P501: Dispose of contents/container to ...
In the 13-week feeding study in rats (4, 20, 100 and 500 mg/kg diet; 0.4, 2, 10 and 50 mg/kg bw), severe histopathological changes were noted in the kidneys and the adaptive changes were observed in the liver and thyroid with dose dependency. The focal and severe injuries in the proximal tubules (anisokaryosis and necrosis) in the kidneys were found at 2 mg/kg bw which corresponded to Category 1 of GHS classification. The changes in the thyroid included increased epithelial height by multifocal papillary proliferation and reduced colloid density were observed in males at 2 mg/kg bw which corresponded to Category 1of GHS classification and in females at 50 mg/kg/ bw which corresponded to Category 2 (IARC vol. 79 (2001)). In the 13-week oral dose study in dogs (0.2, 2 and 5 mg/kg bw), increase in alkaline phosphatase activity as well as mild to moderate histopathological changes in the liver, thyroid and kidneys were seen at 5 mg/kg bw which corresponded to Category 1 of GHS classification. Thus, the substance was classified as Category 1 (kidney). Moreover, as the findings in the liver, centrilobular hepatocellular hypertrophy and fatty intracytoplasmic inclusion bodies were observed at dietary concentrations of 50 - 200 ppm (converted values as the actual intake: 5 - 20 mg/kg/day) in the 2 to 9 months feeding study in rats (DFGMAK-Doc. 19 (2003)), and centrilobular hepatocellular hypertrophy and peripheral margination of increase in eosinophilic cells and basophilic granules were observed at dietary concentrations of 100 - 400 ppm (converted values as the actual intake: 5 - 20 mg/kg/day) in the life-time feeding study in rats (EHC 45 (1984)). Since these changes were observed from the dose range equivalent to Category 1, the substance was classified as Category 1 (liver). Furthermore, as the thyroids, significant increase in TSH (thyroid stimulating hormone) was found in the oral administration study in rats administered at 100 mg/kg bw for three days and thereafter at 75 mg/kg bw for 25 days (IARC vol. 79 (2001)), and increased epithelial height by multifocal papillary proliferation and reduced colloid density in the thyroid were observed in males at 2 mg/kg bw which corresponded to Category 1 of GHS classification (IARC vol. 79 (2001)). Thus, the substance was also classified as Category 1 (thyroid). Otherwise, there was the description that toxic signs such as generalized body tremors, leg paralysis and ataxia, etc. were observed at higher dose levels (1080 - 1112 ppm, converted values as the actual intake: approx. 55 mg/kg/day, equivalent to Category 2) in the 80-week feeding study in rats (NTP TR 37 (1979)). Therefore, the substance was additionally classified as Category 2 (central nervous system).
10 Aspiration hazard Classification not possible - - - - No data available.

ENVIRONMENTAL HAZARDS
Hazard class Classification Symbol Signal word Hazard statement Precautionary statement Rationale for the classification
11 Hazardous to the aquatic environment (Acute) Category 1 Warning H400: Very toxic to aquatic life P273: Avoid release to the environment.
P391: Collect spillage.
P501: Dispose of contents/container to ...
Classified into Category 1 from its 96h-LC50 = 0.0011 mg/L for fish (Cyprinodon variegatus) (EHC 45, 1984).
11 Hazardous to the aquatic environment (Long-term) Category 1 Warning H410: Very toxic to aquatic life with long lasting effects P273: Avoid release to the environment.
P391: Collect spillage.
P501: Dispose of contents/container to ...
Classified into Category 1 since its acute toxicity is Category 1 and it is estimated not to be rapidly degradable (BIOWIN).
12 Hazardous to the ozone layer Classification not possible - - - - This substance is not listed in Annexes to the Montreal Protocol.


NOTE:
* Classification was conducted by relevant Japanese Ministries in accordance with GHS Classification Guidance for the Japanese Government, and is intended to provide a reference for preparing GHS labelling and SDS for users.
* This is a provisional English translation of classification results and is subject to revision without notice.
* The responsibility for any resulting GHS labelling and SDS referenced from this site is with users.

Reference:
Reference Manual

Definitions / Abbreviations

Model Label by MHLW

MHLW Website (in Japanese Only)

Model SDS by MHLW

MHLW Website (in Japanese Only)


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