Registration Dossier - ECHA (2024)

• Substance Identity
• Administrative Information

• GHS
• DSD - DPD
• PBT assessment

• Life Cycle description
  • No identified uses
  • Manufacture
  • Formulation
  • Uses at industrial sites
  • Uses by professional workers
  • Consumer Uses
  • Article service life
• Uses advised against
  • Formulation
  • Uses at industrial sites
  • Uses by professional workers
  • Consumer Uses

• 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
  • Endpoint summary
  • Phototransformation in air
  • Hydrolysis
  • Phototransformation in water
  • Phototransformation in soil
• Biodegradation
  • Endpoint summary
  • Biodegradation in water: screening tests
  • Biodegradation in water and sediment: simulation tests
  • Biodegradation in soil
  • Mode of degradation in actual use
• Bioaccumulation
  • Endpoint summary
  • Bioaccumulation: aquatic / sediment
  • Bioaccumulation: terrestrial
• Transport and distribution
  • Endpoint summary
  • Adsorption / desorption
  • Henry's Law constant
  • Distribution modelling
  • Other distribution data
• Environmental data
  • Endpoint summary
  • Monitoring data
  • Field studies
• 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
  • Endpoint summary
  • Toxicity to soil macroorganisms except arthropods
  • Toxicity to terrestrial arthropods
  • Toxicity to terrestrial plants
  • Toxicity to soil microorganisms
  • Toxicity to birds
  • Toxicity to other above-ground organisms
• Biological effects monitoring
• Biotransformation and kinetics
• Additional ecotoxological information

• Toxicological Summary
• Toxico*kinetics, metabolism and distribution
  • Endpoint summary
  • Basic toxico*kinetics
  • Dermal absorption
• Acute Toxicity
  • Endpoint summary
  • Acute Toxicity: oral
  • Acute Toxicity: inhalation
  • Acute Toxicity: dermal
  • Acute Toxicity: other routes
• Irritation / corrosion
  • Endpoint summary
  • Skin irritation / corrosion
  • Eye irritation
• Sensitisation
  • Endpoint summary
  • Skin sensitisation
  • Respiratory sensitisation
• Repeated dose toxicity
  • Endpoint summary
  • Repeated dose toxicity: oral
  • Repeated dose toxicity: inhalation
  • Repeated dose toxicity: dermal
  • Repeated dose toxicity: other routes
• Genetic toxicity
  • Endpoint summary
  • Genetic toxicity: in vitro
  • Genetic toxicity: in vivo
• Carcinogenicity
• Toxicity to reproduction
  • Endpoint summary
  • Toxicity to reproduction
  • Developmental toxicity / teratogenicity
  • Toxicity to reproduction: other studies
• Specific investigations
  • Neurotoxicity
  • Immunotoxicity
  • Endocrine disrupter mammalian screening – in vivo (level 3)
  • Specific investigations: other studies
  • Phototoxicity in vitro
• Exposure related observations in humans
  • Endpoint summary
  • Health surveillance data
  • Epidemiological data
  • Direct observations: clinical cases, poisoning incidents and other
  • Sensitisation data (human)
  • Exposure related observations in humans: other data
• Toxic effects on livestock and pets
• Additional toxicological data

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

March 24, 1985- April 4, 1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Data source

Materials and methods

Principles of method if other than guideline:

The study is well-documented and performed according to generally accepted scientific standards.

GLP compliance:

yes

Test type:

other: Dose range finding followed by a unique dose application.

Limit test:

yes

Test material

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 5601-49-1, J-243

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Stability under test conditions: There was no apparent change in the physical state of the test article during administration

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Sgarlat's rabbitry, Harvey's Lake, Pennsylvania
- Age at study initiation: no data
- Weight at study initiation: 2 - 3 kg
- Fasting period before study: no data
- Housing: rabbits were individually housed in cages sized in accordance with the 'Guide for the Care and Use of Labratory Animals' of the Institute of Laboratory Resources, National Research Council.
- Diet (e.g. ad libitum): ad libitum, Waye Rabbit Ration
- Water (e.g. ad libitum): ad libitum, fresh tap water
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 °C +/- 3 °C
- Humidity (%): 30 - 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12h light/12 h dark

IN-LIFE DATES: From: March 21, 1985 To: April 4, 1985

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal trunk, abraded area.
- % coverage: No less than 20%
- Type of wrap if used: Gauze, followed by a rubber dam and wrapped with an ace bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Wrappings were removed, no washing done.
- Time after start of exposure: 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 8.0 g/kg
- Constant volume or concentration used: yes

Duration of exposure:

24 hrs

Doses:

1, 3, 5 and 8 g/kg (dose range finding study)
8 g/kg (main study)

No. of animals per sex per dose:

1 male, 1 female (dose range finding)
5 males, 5 females (main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30 minutes, 2 and 4 hours, and then twice daly through 14 days.
- Necropsy of survivors performed: yes, sacrificed by CO2 inhalation
- Other examinations performed: clinical signs, body weight, organ weights

Results and discussion

Preliminary study:

A dose-range-finding study was performed, consisting of 4 groups of two rabbits per group, dosed at 1.0, 3.0, 5.0 and 8.0 g/kg. No mortality was observed.

Mortality:

3 out of 10 rabbits died during the study

Clinical signs:

other: Decreased activity, diarrhea, ptosis, decreased muscle tone, abnormal stance, dypsnea, poor grooming, necrosis and alopecia at the application site, bruxism, red exudate (anal-genital region) and prostration.

Gross pathology:

Necropsy of rabbits dying on study revealed hemorrhages of fascia underlying application site, edematous and congested lungs, pale kidneys, cortical necrosis of the kidneys, discolored ureter and fluid-filled bladder. Terminal necropsy of the surviving animals revealed hemorrhage of fascia and necrosis of skin underlying application site.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based upon the observations made in the study, the estimated LD50 of the test material was determined to be greater than 8.0 g/kg. Therefore, the test substance is considered not to be classified according to CLP regulation .

Executive summary:

In a dose-range-finding screen, four groups of two abraded rabbits per group (one male and one female) were administered the test article at 1.0 / 3.0 / 5.0 and 8.0 mg/kg. None of the rabbits died in the dose-range-finding study.

In an 8.0 mg/kg limit test, one group of ten rabbits (five males and five females) was dermally administered the test article.

Three of the animals died during the study. Signs observed included: decreased activity, diarrhea, ptosis, decreased muscle tone, abnormal gait, abnormal stance, dyspnea, poor grooming, necrosis and alopecia at the applicatio site, bruxism, red exudate (anal-genital region) and prostration.

Necropsy of the animals dying on study revealed hemorrhages of fascia underlying the application site, edematous and congested lungs, pale kidneys, cortical necrosis of the kidneys, discolored ureter and fluid-filled bladder.

Terminal necropsy of the surviving animals revealed hemorrhage of fascia and necrosis of skin underlying the application site.

Based upon the observations made in the definitive acute dermal toxicity study in rabbits, the estimated LD50 for the test article was determined to be greater than 8.0 mg/kg.