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EC number: 445-790-1 | CAS number: 404362-22-7
- 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- from 2012-07-14 to 2012-xx-xx
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP study according to OECD guideline 421
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 421 reproduction/developmental toxicity screening test
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- -
- EC Number:
- 445-790-1
- EC Name:
- -
- Cas Number:
- 404362-22-7
- Molecular formula:
- Component 1: C16H20N2 Components 2 and 3: C24H28N2
- IUPAC Name:
- (2-phenylethyl)[(3-{[(2-phenylethyl)amino]methyl}phenyl)methyl]amine; 1-(3-{[(2-phenylethyl)amino]methyl}phenyl)methanamine
- Test material form:
- other: clear liquid
- Details on test material:
- - Name of test material (as cited in study report): Gaskamine 240
- Physical state: clear liquid
- Analytical purity: 97.73 % (based on the sum of 4 main peaks HPLC(ELSD) Area %)
- Lot/batch No.: 1R101
- Expiration date of the lot/batch: 30-Sep-2012
- Storage condition of test material: at room temperature (20±5 °C) in the dark, under nitrogen gas
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Laboratories, BV, Kreuzelweg 53, 5961 NM Horst / Netherlands
- Age at study initiation: (P) x 10 wks
- Weight at study initiation: (P) Males: 339-385 g; Females: 203-236 g; (F1)
- Fasting period before study: no
- Housing: Individually in Makrolon type-3 cages with wire mesh tops and sterilized standard softwood bedding (‘Lignocel’ J.Rettenmaier & Söhne GmbH & CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba SA, 4303 Kaiseraugst / Switzerland; batch/lot no. 02105120301) with paper enrichment (Envirodri from Lillico, Biotechnology, Surrey / UK), batch/lot no. 100099). During the pre-pairing period, cages with males were interspersed amongst those
holding females to promote the development of regular estrus cycles.
- Diet (e.g. ad libitum): Pelleted standard Harlan Teklad 2914C (batch no. 73/11) rodent maintenance diet (Provimi Kliba SA, 4303 Kaiseraugst / Switzerland) was available ad libitum.
- Water (e.g. ad libitum): Community tap-water from Itingen was available ad libitum in water bottles.
- Acclimation period: 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- peanut oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE
- Justification for use and choice of vehicle (if other than water): for stability of the test item
- Concentration in vehicle: o, 1.25, 3.75 and 10.0 mg/mL/day
- Amount of vehicle (if gavage): 4 mL/kg bw
- Lot/batch no. (if required): Charge 260156161 - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The dose formulations were analyzed by an HPLC method adapted at Harlan Laboratories. The samples (approximately 2 g each) were delivered to the analytical laboratory.
- Details on mating procedure:
- - M/F ratio per cage: 1/1
- Length of cohabitation: 14 days maximum
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After 14 days of unsuccessful pairing replacement of first male by another male with proven fertility.
- Further matings after two unsuccessful attempts: no
- After successful mating each pregnant female was caged (how): no data - Duration of treatment / exposure:
- males: 4 weeks, females: 7 to 9 weeks
- Frequency of treatment:
- once daily
- Duration of test:
- Males were sacrificed after they had been treated for at least 28 days, when no longer needed for the assessment of reproductive effects. Dams and pups were sacrificed on day 4 post partum. If birth did not occur on the expected date (day 21 post coitum), the dam was sacrificed on
day 25 post coitum.
- No. of animals per sex per dose:
- 11
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The highest dose level was chosen with the aim of inducing toxic effects but not death or severe suffering. A descending sequence of dose levels was selected with a view to demonstrating any dose related response. 2.67 to 3 fold intervals were chosen for the descending dose levels.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: once daily
BODY WEIGHT: Yes
- Time schedule for examinations: Males: Recorded on the first day of dosing, once weekly thereafter and at termination. Females: Recorded on the first day of dosing, once weekly thereafter and on days 0, 7, 14 and 20 post coitum, on days 0, 1 and 4 post partum. - Ovaries and uterine content:
- GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the abdominal viscera.
HISTOPATHOLOGY / ORGAN WEIGHTS
The following tissues were prepared for microscopic examination and weighed, respectively: in females (ovaries) that did not give birth and liver of all animals. In addition, microscopic examination of the reproductive organs of all infertile males was made. - Fetal examinations:
- SACRIFICE
- The F1 offspring were sacrificed at 4 days of age.
- These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination) as follows: for any structural changes
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations
HISTOPATHOLOGY / ORGAN WEIGTHS
no data - Statistics:
- The following statistical methods were used to analyze food consumption, body weights and reproduction data:
• Means and standard deviations of various data were calculated.
• The Dunnett-test (many to one t-test) based on a pooled variance estimate was applied if the variables could be assumed to follow a normal distribution for the comparison of the treated groups and the control groups for each sex.
• The Steel-test (many-one rank test) was applied instead of the Dunnett-test when the data could not be assumed to follow a normal distribution.
• Fisher's exact-test was applied if the variables could be dichotomized without loss of information. - Indices:
- ERproductive indices:
Percentage mating = ( Females mated / Females paired) * 100
Fertility index = ( Females achieving a pregnancy / Females paired) * 100
Conception rate = ( Females achieving a pregnancy / Females mated) * 100
Gestation index = ( Number of females with living pups / Females pregnant) * 100
Offspring viability indices:
Viability index = (pups alive before culling on day 4 p.p. / pups born alive) * 100
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes. Remark: LOAEL = 40 mg/kg bw/d
Details on maternal toxic effects:
Abnormal posture or gait, body weight loss and lower food consuption, clay- or tan-colored livers (for more details see RSS Braun 2012 in section 7.8.1 Toxicity to reproduction).
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOEL
- Effect level:
- 15 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- LOAEL
- Effect level:
- 40 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Effect levels (fetuses)
- Dose descriptor:
- NOEL
- Effect level:
- 40 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- In an OECD 421 Reproduction / Developmental Toxicity Screening Study no teratogenic effects observed up to the highest dose level tested of 40 mg/kg bw/d (NOEL).
- Executive summary:
In a Klimisch-1 -rated OECD 421 Reproduction / Developmental Toxicity Screening Study no teratogenic effects were being observed up to the highest dose level tested of 40 mg/kg bw/d (NOEL).
The NOAEL for systemic toxicity in liver has to be based on the gross lesions that were recorded only in a few high dose animals. A correlating increase in glycogen contents was noted in these few males and females although the body weights were decreased in high dose animals. Therefore, a relation to an effect of the test item cannot be excluded definitely at 40 mg/kg bw/day and the NOAEL was established at 15 mg/kg bw/day based on the livers with gross lesions.
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