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EC number: 911-418-6 | CAS number: 55965-84-9
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Carcinogenicity
Administrative data
Description of key information
C(M)IT/MIT was tested in two chronic/carcinogenicity tests by either the oral route (rat) or dermal route (mouse).
Key value for chemical safety assessment
Carcinogenicity: via oral route
Link to relevant study records
- Endpoint:
- carcinogenicity: oral
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 83-5 (Combined Chronic Toxicity / Carcinogenicity)
- Deviations:
- no
- GLP compliance:
- yes
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. 48014
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in water
- Final dilution of a dissolved solid, stock liquid or gel: 30, 100, 300 ppm a.i.
OTHER SPECIFICS: Purity of test material was 14.2% - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Portage Facility, Portage, Michigan, USA
- Age at study initiation: approximately 3 weeks old
- Weight at study initiation: Males: 162 - 282 grams; Females: 122 – 207 grams
- Fasting period before study: Not described
- Housing: Not described
- Diet (e.g. ad libitum): Not described
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not described - Route of administration:
- oral: drinking water
- Vehicle:
- water
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- n/a
- Duration of treatment / exposure:
- 24 months
- Frequency of treatment:
- Continuous
- Post exposure period:
- n/a
- Dose / conc.:
- 30 ppm
- Remarks:
- Nominal based on a.i.
- Dose / conc.:
- 100 ppm
- Remarks:
- Nominal based on a.i.
- Dose / conc.:
- 300 ppm
- Remarks:
- Nominal based on a.i.
- No. of animals per sex per dose:
- 90 males and 80 females/group
- Control animals:
- yes, concurrent vehicle
- other: inorganic stabilizer salt control
- Positive control:
- No
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: clinical signs, daily and physical examinations, weekly
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
- Time schedule for examinations: Weekly
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Yes, prior to study initiation and during the twenty-fourth month of dosing
- Dose groups that were examined: All
HAEMATOLOGY: Yes
- Time schedule for collection of blood: 3, 6, 12, 18 and 24 months
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 20/sex/group
- Parameters checked in table [No.?] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: 3, 6, 12, 18 and 24 months
- Animals fasted: No data
- How many animals: 20/sex/group
- Parameters checked in table [No.?] were examined.
URINALYSIS: Yes
- Time schedule for collection of urine: 3, 6, 12, 18, 24 months of treatment
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Parameters checked in table [No.?] were examined. - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table)
HISTOPATHOLOGY: Yes (see table) - Other examinations:
- Health monitoring (Sentinel animal program) and kidney ultrasonography (conducted on all males during the 6th and 12th months of the study)
- Statistics:
- Distributions of the following parameters were inspected for normality and homogeneity of variance across treatment groups and sampling times: body weights, cumulative body weight changes, feed consumption, water consumption, organ weights, urinalysis, hematology, and clinical chemistry. Square root transformations were used for parameters of the white blood cell differential prior to further analysis. Analysis of variance (or covariance if pre-test scores were available) was used to determine whether or not statistically significant differences existed among the various treatment group means. When significant treatment effects were found, pairwise comparisons of least square means were made between each Kathon biocide-treated group and control using Dunnett's t-test. Statistical significance was indicated when a p-value of 0.05 or less (Dunnett's comparison) was obtained.
- Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreases in body weight and body weight gain at 300 ppm a.i.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Slight decrease in food consumption was seen in 300 ppm male animals
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased water consumption in all dose levels
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- effects observed, treatment-related
- Description (incidence and severity):
- Gastric irritation
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Gastric irritation, Adverse effects were seen in kidneys and in adrenal gland of male and female
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Details on results:
- BODY WEIGHT AND WEIGHT GAIN
There were no treatment-related effects on body weight or body weight gain at doses up to and including 100 ppm.
Decreases in body weight and body weight gain were seen in 300 ppm animals throughout the study and were considered most likely secondary to decreases in water consumption.
FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
There were no treatment-related effects on food consumption at doses up to and including 100 ppm. A slight decrease in food consumption was seen in 300 ppm male animals, likely associated with decreased water consumption in this group. No treatment-related effects on food consumption were seen in females.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
A treatment-related and concentration-dependent decrease in water consumption was seen in both sexes in all Kathon biocide-treated groups throughout the study. These decreases ranged from 0-22 % at 30 ppm, 3-30 % at 100 ppm and 15-40 % at 300 ppm ai. These decreases appear to be due to the unpalatability of the Kathon biocide and not its inorganic stabilizer salts since the water consumption in Group 2 (salt control) was comparable to the tap water control throughout the study. Based on the average daily water consumption, the 300 ppm dose was judged to be a maximum tolerated dose.
URINALYSIS
No changes in urinary parameters were seen which were considered indicative of treatment-related systemic toxicity. Increases in urinary specific gravity were observed sporadically in mid- and high-dose rats at 3 and 6 months only. These increases are not unexpected, given decreased water consumption seen in these groups. No treatment related effects were seen via ultrasound in the renal pelvis of rats at any dose level.
GROSS PATHOLOGY
Gastric irritation at 100 and 300 ppm.
HISTOPATHOLOGY: NON-NEOPLASTIC
Treatment-related morphologic changes were observed in the stomach and occurred in both sexes at 100 and 300 ppm. The primary effect noted was gastric irritation which was reflected by thickening of the forestomach mucosa due to hyperplasia and hyperkeratosis of the squamous mucosa. Focal necrosis of the superficial glandular mucosa and edema and inflammatory cell infiltration in the forestomach submucosa were seen in the 300 ppm males.
Treatment-related morphologic changes were observed in both sexes in mid and high dose groups, in kidneys (from 30 ppm ai to 300 ppm ai) and in the adrenal gland of both sexes at the higher dose (300ppm ai).
OTHER FINDINGS
There were no treatment-related effects at any dose at any time point seen via ultrasound of the kidneys of male rats. - Relevance of carcinogenic effects / potential:
- n/a
- Dose descriptor:
- NOEL
- Effect level:
- 300 ppm (nominal)
- Based on:
- act. ingr.
- Sex:
- male/female
- Remarks on result:
- other: Effect type: carcinogenicity (migrated information)
- Dose descriptor:
- NOEL
- Effect level:
- 30 ppm (nominal)
- Based on:
- act. ingr.
- Sex:
- male/female
- Basis for effect level:
- other: gross pathology
- Remarks on result:
- other: Effect type: toxicity (migrated information)
- Conclusions:
- Chloro-methylisothiazolone/methylisothiazolone produced no evidence of carcinogenicity at doses up to and including the highest dose tested (300 ppm a.i or 17 to 27 mg a.i./kg body weight /day).
- Executive summary:
OECD 453, US EPA 83-5, Combined chronic/carcinogenicity study in rats with analytical confirmation of drinking water concentrations. Administration of Kathon biocide to male and female rats in the drinking water for 24 months at concentrations up to and including 300 ppm active substance showed no effects on the type or incidence of neoplasms in any group. No systemic effects. Treatment-related morphologic changes were observed only in the stomach of both sexes in mid and high dose groups. Gastric irritation was the primary effect observed. No adverse effects on the histopathology of any tissues/organs distant from the site of dosing.No treatment-related signs of toxicity were seen at 30 ppm active ingredient (2.0 mg a.i./kg b.w./day in males and 3.1 mg a.i./kg b.w./day in females), the no-observed-effect level (NOEL) in this study.
Reference
Results of carcinogenicity study in rats via drinking water
Parameter |
Control |
Salt control |
Low dose (30 ppm) |
Medium dose (100 ppm) |
High dose (300 ppm) |
|||||
|
ma |
fa |
ma |
fa |
ma |
fa |
ma |
fa |
ma |
fa |
Number of animals examined |
90 |
80 |
90 |
80 |
90 |
80 |
90 |
80 |
90 |
80 |
MortalityAdjustedsurvival, 24 months |
36 % |
35 % |
41 % |
35 % |
30 % |
33 % |
37 % |
38 % |
46 % |
32 % |
Body weight |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
dec. |
dec. |
Food consumption |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
-- |
dec. |
dec. |
Decreasewater consumption |
-- |
-- |
-- |
-- |
0-22 % |
3-30 % |
15-40 % |
|||
Organ: forestomach |
|
|
|
|
|
|
|
|
|
|
Gross pathology* Organ: forestomach gastric irritation Organ : kidneys Glomerulonephrosis Organ : adrenal gland, hypertrophy |
-- |
-- |
-- |
-- |
--
inc
inc.
|
--
inc
-- |
inc.
inc.
inc.
|
inc.
inc.
-- |
inc.
inc.
inc.
|
inc.
inc.
inc.
|
Microscopic pathology* Hyperplasia |
1/24 |
0/20 |
3/27 |
0/20 |
1/19 |
0/20 |
3/25 |
5/21 |
18/30 |
8/19 |
* specify effects; for different organs give special findings in the order organ weight, gross pathology and microscopic pathology if there are effects
a give number of animals affected/total number of animals, percentage
-- no change in controls versus dosed group
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 17.2 mg/kg bw/day
- Study duration:
- chronic
- Species:
- rat
- System:
- gastrointestinal tract
- Organ:
- other: forestomach
Carcinogenicity: via inhalation route
Endpoint conclusion
- Endpoint conclusion:
- no study available
Carcinogenicity: via dermal route
Link to relevant study records
- Endpoint:
- carcinogenicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 451 (Carcinogenicity Studies)
- Deviations:
- yes
- Remarks:
- only male mice were used and only one dose of TS
- GLP compliance:
- yes
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. MH31:9E
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable at room temperature
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in water
- Final dilution of a dissolved solid, stock liquid or gel: 400 ppm a.i.
OTHER SPECIFICS: Purity of test material was 1.5% (of which, 75 % CMIT, 25 % MIT) - Species:
- mouse
- Strain:
- CD-1
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River, Portage, Michigan, USA
- Age at study initiation: Approximately one month
- Weight at study initiation: 23-31 g
- Fasting period before study:
- Housing: Not described
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Not described - Route of administration:
- dermal
- Vehicle:
- water
- Details on exposure:
- TEST SITE
- Area of exposure: 2 x 3 cm
- % coverage: Not described
- Type of wrap if used: Not described
- Time intervals for shavings or clipplings: Not described
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not described
- Time after start of exposure: Not described
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 25 µL/animal (10 µg/animal) a.i.
- Concentration (if solution): 400 ppm a.i.
- Constant volume or concentration used: yes
USE OF RESTRAINERS FOR PREVENTING INGESTION: Not described - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 30 months
- Frequency of treatment:
- 3 days/week
- Post exposure period:
- No
- Dose / conc.:
- 10 other: µg/animal (nominal)
- No. of animals per sex per dose:
- 40
- Control animals:
- yes, concurrent vehicle
- Positive control:
- 3-methylcholanthrene (1000 ppm a.i.)
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: No data
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily
DERMAL IRRITATION (if dermal study): Yes / No / No data
- Time schedule for examinations:
BODY WEIGHT: Yes
- Time schedule for examinations: Yes, weekly for first 13 weeks and monthly thereafter
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: No
CLINICAL CHEMISTRY: No
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (see table)
HISTOPATHOLOGY: Yes (see table) - Other examinations:
- No
- Statistics:
- Overall survival distribution among the groups was compared using both the generalized Wilcoxon test and the log rank test. Thirty-month survival was analysed by a chi-square test (water control group versus Kathon™ CG-treated group) or Fisher’s exact test (3-MC group versus water control group or the Kathon™ CG-treated group).
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Brown staining, eschar and/or dessication, flaking of skin at application site of Kathon™ CG treated mice
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- mortality observed, treatment-related
- Description (incidence):
- Brown staining, eschar and/or dessication, flaking of skin at application site of Kathon™ CG treated mice
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Brown staining, eschar and/or dessication, flaking of skin at application site of Kathon™ CG treated mice
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- not examined
- Details on results:
- HISTOPATHOLOGY: NON-NEOPLASTIC
The treated skin of the Kathon™ CG animals did show focal or multifocal epidermal necrosis, hyperplasia, hyperkeratosis, eschar, dermal inflammation, and increased dermal collagen.
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
No treatment-related findings were evident at necropsy in the Kathon™ CG-treated animals. Histopathologic evaluation revealed no indications of a treatment-related increased incidence of neoplasms either at the application site or systemically in the Kathon™ CG-treated animals. The incidence of systemic neoplasms was similar in the water control and Kathon™ CG-treated group. - Key result
- Dose descriptor:
- NOAEL
- Sex:
- male
- Remarks on result:
- not determinable due to absence of adverse toxic effects
- Conclusions:
- No adverse effects were seen on the histopathology of any tissues/organs distant from the site of dosing.
- Executive summary:
The mouse skin painting carcinogenicity study was initiated prior to the adoption of carcinogenicity study guidelines. However, the principles of OECD Guideline 451, in general, were followed with the deviations as noted, below. Kathon™CG, when applied dermally to the closely clipped skin on the backs of male CD-1 mice at a concentration of 400 ppm active substance and at a dose of 25 µL 3 times per week for 30 months, showed no local or systemic tumorigenic potential. No adverse effects were seen on the histopathology of any tissues/organs distant from the site of dosing.
Reference
Endpoint conclusion
- Endpoint conclusion:
- no adverse effect observed
- Study duration:
- chronic
- Species:
- mouse
Mode of Action Analysis / Human Relevance Framework
C(M)IT/MIT produced no evidence of carcinogenicity (ie., no treatmentrelated increase in the type or incidence of neoplasms in any group) up to the highest tested doses in these studies.
Justification for classification or non-classification
CMIT/MIT carries a mandatory classification in accordance with Annex VI Regulation EC 1272/2008 and is not classified for carcinogenic effects.
Additional information
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