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EC number: 242-640-5 | CAS number: 18871-14-2
- 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

Toxicity to reproduction
Administrative data
- Endpoint:
- fertility, other
- Remarks:
- Repeated-dose 90-day dermal toxicity study.
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- Januari 2014 - November 2014
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 015
- Report date:
- 2015
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 411 Subchronic dermal toxicity: 90-day study (1981)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: EU method B.28 sub-chronic dermal toxicity study (2008)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Pyranol
- IUPAC Name:
- Pyranol
- Reference substance name:
- 63500-71-0; 65418-70-4 (trans); 65418-69-1 (cis)
- IUPAC Name:
- 63500-71-0; 65418-70-4 (trans); 65418-69-1 (cis)
- Test material form:
- other: liquid (colorless, clear)
- Details on test material:
- - Name of test material (as cited in study report): Pyranol
- Physical state: liquid
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Crl:WI(Han)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services GmbH, Sulzfeld, Germany
- Age at study initiation: 63 ± 1 days
- Weight at study initiation: Males: 245.0-275.6 g; Females: 170.4-206 g
- Fasting period before study: no
- Housing: individually in polysulfonate cages (motor activity measurements were conducted in polycarbonate cages)
- Use of restrainers for preventing ingestion (if dermal): yes, covered for at least 6 hours after application using a semiocclusive dressing, consisting of 4 layers of porous gauze dressing
- Diet: ad libitum; ground Kliba maintenance diet mouse/rat “GLP”, meal, supplied by Provimi Kliba SA, Kaiseraugst, Switzerland
- Water: ad libitum, water bottles
- Acclimation period: 6 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): set at 20-24
- Humidity (%): set at 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 27 January 2014 To: 30 April 2014
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- corn oil
- Details on exposure:
- TEST SITE
- Area of exposure: 10% of the body surface
- Type of wrap if used: The skin was covered for at least 6 hours after application using a semiocclusive dressing, consisting of 4 layers of porous gauze dressing (Absorbent gauze EP supplied by Lohmann GmbH & Co. KG, Neuwied, Germany) and a stretch bandage (Fixomull® stretch [adhesive fleece] supplied by Beiersdorf AG, Hamburg, Germany).
- Time intervals for shavings or clipplings: The animals were reclipped at least once a week (depending on hair growth).
REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin was washed with lukewarm water
- Time after start of exposure: After removal of the dressing.
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The application volume was 4 mL/kg bw, based upon the latest individual body weight determination.
- Concentration (if solution):
VEHICLE
- Justification for use and choice of vehicle (if other than water): no information
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes, semiocclusive dressing. - Details on mating procedure:
- No data on mating. Reproductive parameters investigated in this repeated dose toxicity study are considered for the endpoint reproduction toxicity.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The stability of the test substance in corn oil at room temperature for a period of 8 days was demonstrated during the application period.
The test substance was completely miscible with corn oil and thus a solution. Therefore, the test-substance preparation was considered to be homogenous. Consequently further homogeneity analyses were not carried out.
Concentration control analyses of the test-substance preparations were performed in samples of all concentrations at the start of the application period. - Duration of treatment / exposure:
- 3 months
- Frequency of treatment:
- 5 days per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
100, 300 and 1000 mg/kg bw/day
Basis:
other: dermal application
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: at the request of the sponsor.
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily (working days), once daily (Satudays, Sundays and public holidays)
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Day 0 and subsequently once a week.
BODY WEIGHT: Yes
- Time schedule for examinations: Day 0 and thereafter at weekly intervals.
FOOD CONSUMPTION AND COMPOUND INTAKE: Yes
Food consumption was determined weekly as representative value over a period of 1 day and calculated as mean food consumption in grams per rat and day.
WATER CONSUMPTION AND COMPOUND INTAKE: No
Drinking water consumption was monitored by daily visual inspection of the water bottles for any changes in volume.
OTHER:
FOB, Ophthalmoscopy, clinical chemistry, hematology, organ weights, histopathology. - Oestrous cyclicity (parental animals):
- not examined
- Sperm parameters (parental animals):
- Parameters examined:
testis weight, histopathology (control and high dose groups) of testes, epididymides, prostate, seminal vesicles - Litter observations:
- no
- Postmortem examinations (parental animals):
- SACRIFICE
-All animals at the end of the exposure period (3 months).
GROSS NECROPSY
- Gross necropsy according to guidelines.
HISTOPATHOLOGY / ORGAN WEIGHTS
-According to guidelines. - Postmortem examinations (offspring):
- no
- Statistics:
- Food consumption, body weight, body weight change: A comparison of each group with the control group was performed using DUNNETT's test (twosided) for the hypothesis of equal means.
Weight parameters: Non-parametric one-way analysis using KRUSKAL WALLIS test (two-sided). If the resulting p-value was equal or less than 0.05, a pairwise comparison of each dose group with the control group was performed using WILCOXON test (two-sided) for the equal medians. - Reproductive indices:
- -
- Offspring viability indices:
- -
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- 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
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
Details on results (P0)
No animal died prematurely in the present study. Clinical examinations did not reveal treatment-related, adverse effects up to and including a dose level of
1000 mg/kg bw/day. Although erythema, erosions and scales were most likely related to treatment they were assessed to be non-adverse as they occurred only temporarily for a few days in individual animals.
BODY WEIGHT AND FOOD CONSUMPTION (PARENTAL ANIMALS):
No effects on body weight parameters which were of toxicological concern were observed in this study. Body weight change values were significantly increased in female animals of 1000 mg/kg bw/day on study day 14. The finding was assessed to be incidental and not related to treatment as no clear trend in body weight development occurred. No test substance-related effects on food consumption were obtained. All values were within the range typical for animals of this strain and age.
ORGAN WEIGHTS (PARENTAL ANIMALS):
All mean absolute and mean relative weight parameters did not show significant differences when compared to the control group.
GROSS PATHOLOGY (PARENTAL ANIMALS):
All findings occurred either individually or were biologically equally distributed over control and treatment groups. They were considered to be incidental or spontaneous in origin and without any relation to treatment.
HISTOPATHOLOGY (PARENTAL ANIMALS):
All findings occurred either individually or were biologically equally distributed over control and treatment groups. They were considered to be incidental or spontaneous in origin and without any relation to treatment.
OTHER FINDINGS (PARENTAL ANIMALS):
Concerning clinical pathology, no treatment-related, adverse effects were observed up to and including a dose of the compound of 1000 mg/kg bw/day.
Effect levels (P0)
- 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 treatment-related adverse effects were observed
Results: P1 (second parental generation)
General toxicity (P1)
- Description (incidence):
- No animal died prematurely in the present study.
Results: F1 generation
General toxicity (F1)
- Body weight and weight changes:
- not examined
Effect levels (F1)
- Key result
- Remarks on result:
- other: not relevant
Overall reproductive toxicity
- Key result
- Reproductive effects observed:
- no
Applicant's summary and conclusion
- Conclusions:
- No adverse effects were observed on the reproductive organs of male and female rats in a 90-day dermal repeated dose toxicity study with the read-across substance Pyranol.
- Executive summary:
Pyranol was applied by dermal application to groups of 10 male and 10 female Wistar rats at dose levels of 0 mg/kg bw/day (vehicle control), 100 mg/kg bw/day, 300 mg/kg bw/day and 1000 mg/kg bw/day over a period of 3 months (5 days per week) according to OECD 411. Observations relevant for this endpoint included organ weights testes, adrenal glands and thyroid glands, and histopatological examination (control and high dose animals) of testes, epididymides, prostate, seminal vesicles, uterus, vagina, cervix, ovaries, adrenal gland, pituitary gland and thyroid gland). No treatment-related adverse effects were observed up to and including 1000 mg/kg bw/day, the highest dose tested.
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