Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 619-372-6 | CAS number: 98730-04-2
- 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:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 22 January 1986 to 14 February 1986
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP compliant, guideline study, available as unpublished report, no restrictions, fully adequate for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
- Deviations:
- yes
- Remarks:
- occlusive dressing used
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-2 (Repeated Dose Dermal Toxicity -21/28 Days)
- Deviations:
- no
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- 2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one
- EC Number:
- 619-372-6
- Cas Number:
- 98730-04-2
- Molecular formula:
- C11H11Cl2NO2
- IUPAC Name:
- 2,2-dichloro-1-[(3R)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one; 2,2-dichloro-1-[(3S)-3-methyl-3,4-dihydro-2H-1,4-benzoxazin-4-yl]ethan-1-one
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 of animals: H.A.R.E Inc., Hewitt, NJ, USA
- Age at study initiation: 106-113 days
- Weight at study initiation: males 2.86-3.65 kg; females 2.90-3.43 kg
- Fasting period before study: No
- Housing: Individually
- Diet: Certified Purina Rabbit Chow® #5322 ad libitum
- Water: Tap water ad libitum
- Acclimation period: Approximately 36 days
ENVIRONMENTAL CONDITIONS
- Temperature: 65±5°F
- Humidity: 50±20%
- Air changes (per hr): Not reported
- Photoperiod: 12 hrs dark / 12 hrs light
IN-LIFE DATES: From: 22 January 1986 To: 14 February 1986
Administration / exposure
- Type of coverage:
- occlusive
- Vehicle:
- water
- Details on exposure:
- TEST SITE
- Area of exposure: Approximately 120-240 cm2
- % coverage: Approximately 5-10% of total body surface
- Type of wrap if used: Gauze dressing secured with non-irritating adhesive tape.
- Time intervals for shavings or clippings: Prior to application and as necessary during the study
REMOVAL OF TEST SUBSTANCE
- Washing (if done): Tap water followed by drying with paper towel
- Time after start of exposure: 6 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0 (purified water only), 1, 500, 1010 mg/kg/day
- For solids, paste formed: yes (purified water)
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes (Elizabethan collars) - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- 22 consecutive days
- Frequency of treatment:
- Once daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 1, 500 and 1010 mg/kg/day
Basis:
nominal per unit body weight
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
Examinations
- Observations and examinations performed and frequency:
- CLINICAL OBSERVATIONS: Yes
- Time schedule: Daily during pre-dose period, prior to and regularly after dosing on day 1; prior to dosing, within 30 mins of dosing and 30 mins after end of dosing period, prior to termination
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: Pre-dose, prior to dosing and approximately 30 mins after each application period
BODY WEIGHT: Yes
- Time schedule for examinations: Days -8, pre-dose on day 1, weekly thereafter and prior to necropsy
FOOD CONSUMPTION: Yes
- Time schedule for examinations: Pre-dose Days -8 to 1, weekly thereafter
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Day -7 and Day 22
- Dose groups that were examined: All
PHYSICAL/AUDITORY EXAMINATIONS: Yes
- Time schedule for examinations: Day -14 and Day 20
HAEMATOLOGY: Yes
- Time schedule for collection of blood: Days -7, -6 or -3, test days 21, 22, 23 or 24
- Anaesthetic used for blood collection: No data
- Animals fasted: Yes (16-18 hours)
- How many animals: All
- Parameters examined: Haemoglobin, haematocrit, erythrocytes, leukocytes, differential leukocytes, platelets, prothrombin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Days -7, -6 or -3, test days 21, 22, 23 or 24
- Animals fasted: Yes (16-18 hours)
- How many animals: All
- Parameters examined: Urea nitrogen, creatinine, SGOT, SGPT, alkaline phosphatase, glucose, total protein, albumin, globulin, A/G ratio, total bilirubin, total cholesterol, inorganic phosphate, sodium, calcium, potassium, chloride
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes (all animals) on day 22 or 23
ORGAN WEIGHTS: Yes (all animals)
- Organs weighed: adrenal glands, brain, heart, kidney, liver, ovary, pituitary, testis
HISTOPATHOLOGY: Yes (all animals)
- Organs/tissues examined: Liver, kidney, organs showing gross lesions or changes in size, skin (treated and untreated) - Statistics:
- Body weight, food consumption, haematology, clinical chemistry and organ weight data were analysed for each sex separately. Tests for outliers and tests for homogeneity of variance were done. If the model assumptions were met, Dunnett's test was used. Otherwise appropriate ad-hoc analyses including data transforms, nonparametric tests and tests without assuming the homogeneity of group variance were performed. Nonparametric tests also used when parameters known not to be normally distributed.
Microscopic findings analysed separately for each sex by Fisher's Exact test and for both sexes by computing the convolved probabilities.
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Dermal irritation:
- no effects observed
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- effects observed, treatment-related
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY: No mortalities. Clinical signs including inappetence, diarrhoea, soft faeces, and few or no faeces were observed in all groups including control groups. Since the incidence was low and no time or dose-relationships were established, the findings were considered not to be treatment-related.
BODY WEIGHT: Body weight development was comparable between all groups. The slight decrease in mean body weight of top dose males was due to one rabbit only (body weight loss of 260g, 8.1%).
CLINICAL CHEMISTRY: There was slightly decreased blood urea nitrogen in top dose males. In the absence of any meaningful correlation to other clinical chemistry parameters, this was considered to be of no toxicological relevance.
ORGAN WEIGHTS: There was a statistically significant decrease of the mean relative pituitary weights in low dose females, which in absence of any microscopic findings and dose-relationship was considered incidental.
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 1 010 other: mg/kg
- Sex:
- male/female
- Basis for effect level:
- other: No toxicologically significant treatment-related findings at highest dose tested
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- Dermal administration of benoxacor at dose levels up to 1010 mg/kg revealed no significant treatment-related findings. Therefore, the NOEL for dermal administration in this study was 1010 mg/kg.
- Executive summary:
- Benoxacor was administered topically to intact skin under occlusive dressings, for 6 hours per day, to groups of rabbits at doses of 1, 500 or 1010 mg/kg/day for a minimum of 22 consecutive days. Standard parameters were investigated (clinical signs, dermal observations, body weights, food consumption, haematology, clinical chemistry, ophthalmoscopy, organ weights and gross pathological examinations). No treatment-related dermal effect, gross pathology changes or microscopic abnormalities were found. Benoxacor was found to be essentially non-toxic when administered topically at dose levels of up to 1010 mg/kg/day. The no observed effect level (NOEL) was considered to be 1010 mg/kg/day.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.