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EC number: 428-040-8 | CAS number: 138261-41-3
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 29. Jun - 22. Jul 1988
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- guideline study with acceptable restrictions
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 990
- Report date:
- 1990
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Version / remarks:
- 1981
- Deviations:
- yes
- Remarks:
- methodological deficiencies (treatment time was shorter (15 days))
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
- Version / remarks:
- 1982
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- yes
Test material
- Reference substance name:
- -
- EC Number:
- 428-040-8
- EC Name:
- -
- Cas Number:
- 138261-41-3
- Molecular formula:
- C9H10ClN5O2
- IUPAC Name:
- 2-chloro-5-{[2-(nitroimino)imidazolidin-1-yl]methyl}pyridine
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Interfauna, UK Limited, Huntingdon, England
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 10 - 13 weeks
- Weight at study initiation: 2.65 - 3.43 kg (females), 2.93 - 3.09 kg (males)
- Housing: individually in Cellidor Rabbit cages with bedding (low-dust wood granulate from Ssniff Spezialdiaten GmbH, Soest)
- Diet: "ssniff K Alleindiät für Kaninchen" (Ssniff Spezialdiäten GmbH, Soest/Westfalen, Germany), given daily with automatic rabbit feeders
- Water: tap water, ad libitum
- Acclimation period: 15 days
DETAILS OF FOOD AND WATER QUALITY: The water was checked regularly, no influence on the objective of the study was indicated
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): approx. 50%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 29. Jun To: 22. Jul 1988
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- other: 2% (v/v) Cremophor EL in physiological saline solution
- Details on exposure:
- TEST SITE
- Area of exposure: Backs and flanks
- % coverage: > 10
- Type of wrap if used: the test article was covered with a muslin cloth, that was fixed with adhesive tape (Fixomullstretch: Beiersdorf AG, Hamburg)
- Time intervals for shavings or clipplings: one day before starting treatment, then twice weekly
REMOVAL OF TEST SUBSTANCE
- Washing: soap and water
- Time after start of exposure: 6 h
TEST MATERIAL
- Amount applied: 1000 mg/kg bw/day
- Concentration: 40%
- Constant volume or concentration used: yes
- For solids, paste formed: yes
VEHICLE
- Justification for use and choice of vehicle: not specified
- Amount applied: 1.5 mL/kg bw formulation agent
- Concentration (if solution): 2% (v/v) Cremophor EL in physilogical saline solution
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test article in the application formulation was confirmed analytically for 0 and 24 h, resulting in 95.4% and 95.7% of the nominal dose for 0 and 24 h, respectively.
- Duration of treatment / exposure:
- 15 days
- Frequency of treatment:
- 5 days/week
Doses / concentrations
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 5
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: The dose was set on the basis of the results of a preliminary study performed on the rabbit (study no: T4027690)
- Fasting period before blood sampling for clinical biochemistry: not reported - Positive control:
- no
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least once daily
DETAILED CLINICAL OBSERVATIONS: No data
DERMAL IRRITATION: Yes
- Time schedule for examinations: daily
BODY WEIGHT: Yes
- Time schedule for examinations: prior to start of the experiment and weekly thereafter (on Days 0, 7, 14, 22 and 23)
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
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: Yes
- Time schedule for collection of blood: before commencement and after the three-week treatment.
- Anaesthetic used for blood collection: no data
- Animals fasted: not reported
- How many animals: all animals
- Parameters checked: erythrocyte and leucocyte count, hemoglobin, MCV (calculation of mean corpuscular volume of individual erythrocytes), hematocrit, thrombocyte count, MCH (mean hemoglobin content of individual erythrocytes), MCHC (mean hemoglobin concentration of erythrocytes), differential blood count
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: as for hematology
- Animals fasted: no data
- How many animals: all animals
- Parameters checked: Aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, urea, glucose, creatinine, bilirubin, total protein, cholesterin, inorganic phosphate, sodium, potassium, calcium, chloride;
- Time schedule for collection of liver tissue: after necropsy
- How many animals: all animals
- Parameters checked: N-demethylase, O-demethylase, cytochrome P-450, triglycerides
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
- Organs fixed in Bouin's fluid: treated and untreated skin, thyroids, lung, heart, liver, spleen, kidneys, adrenals, testes, epididymides, ovaries, uterus, sternum
- Organs fixed in formol calcium: liver, kidney
- absolute and relative organ weights recorded for: brain, thyroids, heart, lung, liver, kidneys, adrenals, spleen, testes, ovaries
HISTOPATHOLOGY: Yes
- Organs checked: treated and untreated skin, thyroids, lung, heart, liver, spleen, kidneys, adrenals, testes, epididymides, ovaries, uterus, sternum - Statistics:
- Mean and standard deviation were calculated for food consumption, body weights, and for hematological observations and clinical chemistry. Groups were compared using the two-tailed U Test according to Mann and Whitney and Wilcoxon. Significance was defined as p < 0.05
Results and discussion
Results of examinations
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Soft feces was observed on Day 7 in one male animal of the control group and reduced food intake, stiff head position, transfixed bulging eyes, open mouth, salivation and wet nose in one female of the control group (caused by illness)
- Dermal irritation:
- no effects observed
- Description (incidence and severity):
- Redness and skin fold measurements did not differ for control and treated animals. Summarized data can be found in Attachment 1 and 2 in the attached background material.
- Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- Control: One female was sacrificed (Day 3) because of a fractured femur (the female was replaced)
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The body weights of the treated animals did not significantly differ from those of the control group.
- Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Increased food consumption in treated males vs control animals in the first week (3.7%, statistically significant) were observed. Further, reduced food consumption in one control female on Day 14 caused by an illnes was evident.
- Food efficiency:
- not examined
- Description (incidence and severity):
- not applicable
- Water consumption and compound intake (if drinking water study):
- not examined
- Description (incidence and severity):
- not applicable
- Ophthalmological findings:
- not examined
- Description (incidence and severity):
- not applicable
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- not applicable
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- not applicable
- Endocrine findings:
- not examined
- Description (incidence and severity):
- not applicable
- Urinalysis findings:
- not examined
- Description (incidence and severity):
- not applicable
- Behaviour (functional findings):
- not examined
- Description (incidence and severity):
- not applicable
- Immunological findings:
- not examined
- Description (incidence and severity):
- not applicable
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Description (incidence and severity):
- - 1000 mg/kg bw: absolute and relative brain weight increased in males (7.3 and 6.8%, respectively), reduced absolute ovary weight (females, 35.3%), all compared to controls
Since these finidngs were slight, they were considered incidental. - Gross pathological findings:
- no effects observed
- Description (incidence and severity):
- No difference was found between the control and the treatment group.
- Neuropathological findings:
- not examined
- Description (incidence and severity):
- not applicable
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- not applicable
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- not applicable
- Other effects:
- not examined
- Description (incidence and severity):
- not applicable
Effect levels
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effects observed up to and including this dose (highest dose tested)
Target system / organ toxicity
- Key result
- Critical effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- No dermal irritation or any sign of toxicity was observed in this repeated dose study over 15 days with 1000 mg/kg bw/day of the test substance applied to the skin of rabbits. Accordingly, the NOAEL is set at 1000 mg/kg bw/day. The study was conducted according to OECD Guideline 410 but the application duration was shorter than suggested (15 days instead of at least 21 days). Therefore, the study is considered reliable with restrictions. However, as no signs indicating a toxic effect were observed, the NOAEL is acceptable.
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