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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 610-104-3 | CAS number: 43100-47-6
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: study according to GLP and OECD guideline
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Qualifier:
- according to guideline
- Guideline:
- other: US EPA OPPTS 870.3650, Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: US EPA OPPTS 870.3550, Reproduction/Develomental Toxicity Screening Test
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- testing lab.
- Limit test:
- no
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: males approx. 11 weeks, females approx. 12 weeks
- Housing: groups of 5 animals of the same sex (pre-mating), females were caged with males on a one-to-one basis (mating), males were housed in home cage at a maximum of 5/cage, females were individually housed (post-mating)
- Diet: ad libitum
- Water: tap water ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-24
- Humidity (%):40-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: gavage
- Vehicle:
- polyethylene glycol
- Remarks:
- 400, specific gravity 1.125
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Formulations (w/w) were prepared daily within 6 hours prior to dosing and were homogenized to a visually acceptable level.
VEHICLE
- Justification for use and choice of vehicle (if other than water): Based on trial formulations performed at WIL Research Europe
- Amount of vehicle (if gavage): 5ml/kg bw - Details on mating procedure:
- - M/F ratio per cage: one-to-one
- Length of cohabitation: max 14 days, up to the detection of sperm in the vaginal smear
- Proof of pregnancy: sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged: single - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses were conducted on a single occasion during the treatment phase (18 February 2015). The concentrations analyzed in the formulations were in agreement with the target concentrations (i.e. mean accuracies between 85% and 115%). The formulations of the high and low dose groups were assessed for homogeneity and were found to be homogenous. Formulations were stable at room temperature for at least 6 hours.
- Duration of treatment / exposure:
- males: 31 days (2 weeks prior to mating, during mating, and up to the day before necropsy)
females: 40-53 days (2 weeks prior to mating, during mating, during post-coitum, and during at least 4 days of lactation); exception: 3 females (1 in group 3 and 2 in group 4) were not dosed on day 21 or 22 post coitum since they were littering at the time of dosing. - Frequency of treatment:
- daily
- Details on study schedule:
- Parental males and females were treated for at least two weeks prior to mating for a maximum of 2 weeks. Males were sacrificed after mating, but not before treatment for at least 28 days. Females were sacrificed after at least 4 days of lactation and were treated continuously up to the day prior to necropsy with the exception of three females which were left untreated for one day because they littered during the treatment time.
- Remarks:
- Doses / Concentrations:
100, 300, 1000 mg/kg bw/d
Basis:
actual ingested - No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: at least twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: on the first day of exposure and weekly thereafter. Mated females were weighed on Days 0, 4, 7, 11, 14, 17 and 20 post-coitum and during lactation on Days 1 and 4. Live pups were weighed on Days 1 and 4 of lactation.
FOOD CONSUMPTION :
Weekly, except for males and females which were housed together for mating and for females without evidence of mating. Food consumption of mated females was measured on Days 0, 4, 7, 11, 14, 17 and 20 post-coitum and on Days 1 and 4 of lactation.
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: on the day of scheduled necropsy
- Anaesthetic used for blood collection: Yes (isoflurane)
- Animals fasted: Yes (overnight)
- How many animals: 5 animals/sex/group
- Parameters examined: white blood cells, differential leukocyte count, red blood cells, reticulocytes, red blood cell distribution width, haemoglobin, haematocrit, MCV, MCH, MCHC, platelets, prothrombin time, activated partial thromboplastin time
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on the day of scheduled necropsy
- Animals fasted: Yes (overnight)
- How many animals: 5/sex/group
- Parameters examined: ALAT, ASAT, ALP, total protein, albumin, total bilirubin, urea, creatinine, glucose, cholesterol, sodium, potassium, chloride, calcium, inorganic phosphate, bile acids
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: males during week 4 of treatment, females from lactation day 4 onward (before blood sampling)
- Dose groups that were examined: 5 animals/sex/group
- Battery of functions tested: sensory activity / grip strength / motor activity
OTHER:
- pup mortality was determined on day 1 of lactation and daily thereafter.
- cliinical signs for pups were recorded at least once daily
- sex was determined for all pups on days 1 and 4 of lactation - Postmortem examinations (parental animals):
- yes, see section 7.5.1 (repeated dose toxicity)
- Postmortem examinations (offspring):
- Pups surviving to planned termination were killed by decapitation on Days 5-7 of lactation.
All pups were sexed and descriptions of all external abnormalities were recorded. The stomach of pups not surviving to the scheduled necropsy date was examined for the presence of milk, if possible. If possible, defects or cause of death were evaluated. - Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- minimal hepatocellular hypertrophy in males
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Dose descriptor:
- NOEL
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Remarks on result:
- other: Generation: reproductive (migrated information)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Reproductive effects observed:
- not specified
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 000 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- study according to GLP and guideline, Klimisch 1
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
A combined repeated dose/reproductive toxicity testing was conducted according to OECD testing guideline 422 (BASF 2015). Male and female rats received daily doses of 0, 100, 300, or 1000 mg/kg bw/d Ligand TFME in polyethylene glycol 400 via gavage (10 animals per sex per dose). Two weeks after start of treatment, males and females of the same dose level were mated on a one-to-one basis for a maximum of two weeks, pairs were separated after verification of mating. Males were analyzed after 31 days continuous treatment, while females were allowed to litter and were sacrificed on postnatal day 5-7 after 40-53 days of continuous treatment. All pups surviving were terminated on Days 5-7 of lactation. All progeny was sexed and external abnormalities were recorded. Parental animals were subjected to gross pathology and organs were fixed and embedded for histopathology (results see section 7.5 – Repeated dose toxicity). Treatment did not result in mortality or signs of systemic toxicity, and no effects on body weight gain or food consumption were observed. The litter sizes and pregnancy rates were comparable between the dose level groups. Gestation index and duration, parturition, maternal care and early postnatal pup development were unaffected by treatment. External macroscopic inspection of progeny did not reveal treatment-related findings. Therefore, the NOAEL for reproductive toxicity, rat, was determined to be ≥1000 mg/kg bw/d.
Short description of key information:
No impact on fertility was observed in an OECD TG 422 study.
Justification for selection of Effect on fertility via oral route:
study according to GLP and guideline
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
The current data do not fulfill the criteria for classification according to Regulation (EC) 1272/2008 or Regulation 67/548/EEC, thus a non-classification for Ligand TFME-DPP is warranted.
Additional information
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.