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EC number: 222-793-4 | CAS number: 3615-41-6
- 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
Description of key information
Feeding Study, equivalent to OECD 415; rats. NOAEL >1%. No effects were observed in reproductive parameters examined at the highest concentration tested. Reliability = 2.
Link to relevant study records
- Endpoint:
- one-generation reproductive toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Reason / purpose for cross-reference:
- read-across: supporting information
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- yes
- Species:
- rat
- Strain:
- other: Crl:CD(SD)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: (P) 6 wks
- Weight at study initiation: (P) Males: 202–239 g; Females: 166–204 g
- Fasting period before study: no
- Housing: Animals, including F1 pups post-weaning, were individually housed in suspended, stainless steel, wire-mesh type cages, except during mating, near parturition, and during lactation. Rats were housed two per cage (one per sex) during the mating period.
- Diet: Meal Lab Diet Certified Rodent Diet #5002 (ad libitum)
- Water: tap water (ad libitum)
- Acclimation period: 1 week
ENVIRONMENTAL CONDITIONS
- Temperature: 20–26 °C
- Humidity: 30–70%
- Photoperiod (hrs dark / hrs light): 12/12 - Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- TEST SUBSTANCE PREPARATION
- Preparation frequency: weekly
- Preparation details: administered in the diet
- Adjusted for purity: no - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: 7 days
- Proof of pregnancy: not reported
- After successful mating each pregnant female was caged (how): Females were individually housed in plastic cages containing wood chip bedding on approximately gestational day (GD) 20 and were allowed to deliver their litters naturally. - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- In the reproduction study, dosing of P females started 28 days prior to mating and continued throughout mating, gestation, lactation, and weaning of the F1 generation. The P males were exposed only during mating.
- Frequency of treatment:
- Daily in feed
- Details on study schedule:
- - Age at mating of the mated animals in the study: 7 weeks
- Dose / conc.:
- 0.25 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 0.5 other: %
- Remarks:
- nominal in diet
- Dose / conc.:
- 1 other: %
- Remarks:
- nominal in diet
- No. of animals per sex per dose:
- 26 male and female rats
- Control animals:
- yes, plain diet
- Details on study design:
- - Dose selection rationale: The concentration levels were selected based on a previous preliminary study in which no compound-related effects were observed in P females or their offspring following maternal dosing at the same concentrations for 14 days starting from PND 7. The highest dietary concentration of 1% was selected as the top dose to allow for a sufficient margin of safety when compared to potential human infant exposures.
- 13 Week Feeding Study and Recovery Group: At weaning on PND 21, selected F1 pups were weighed and observed individually, and one male or one female from each litter in each group was randomly selected to continue onto the 13-week phase. The control and high-dose group consisted of 30 animals of each sex per group, while the low- and mid-dose groups consisted of 20 animals of each sex per group. After 13 weeks of administration, 10 animals of each sex of the control and high-dose groups were selected to continue on to the one-month recovery period. - Parental animals: Observations and examinations:
- In-life examinations on P females consisted of the following examinations and measurements: morbidity and mortality observations, detailed clinical examinations, body weights, body weight change, food consumption, food efficiency, compound consumption, reproductive performance, and parturition and litter observations. Examinations in P males were conducted for health purposes only (limited to morbidity and mortality observations, detailed clinical examinations, and body weight).
- Litter observations:
- STANDARDISATION OF LITTERS
- On post-natal day (PND) 0, eight pups (four males and four females) per litter were randomly selected for inclusion in the study. On PND 4, litters were weighed and culled to include only the selected pups.
PARAMETERS EXAMINED
- Pups were individually weighed and a gross examination was conducted on PND 0, 4, 7, 14, and 21. In-life examinations on F1 animals consisted of the following examinations and measurements: morbidity and mortality observations, cageside clinical observations, detailed clinical examinations, ophthalmoscopic examinations, body weights, body weight change, food consumption, food efficiency, and compound consumption. Neurobehavioral evaluations [functional observational battery (FOB) tests and locomotor activity tests] and routine clinical pathology (haematology, coagulation, clinical chemistry, and urinalysis) were performed in F1 animals. - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: P males were euthanized after completion of the mating period without further examination.
- Maternal animals: All P females were euthanized and subjected to necropsy on PND 22.
GROSS NECROPSY
- All necropsied P females were examined carefully for external abnormalities, including palpable masses, and were subjected to a full and detailed macroscopic examination of organs and tissues and the results recorded.
HISTOPATHOLOGY / ORGAN WEIGHTS
- Organs and tissues from P females, were fixed in 10% neutral buffered formalin. Formalin was infused into the lungs via the trachea and into the urinary bladder. The eye (with) optic nerve, testes, and epididymides were fixed in a modified Davidson’s fixative. Target organs, gross lesions, and tissue masses with regional lymph nodes also were collected and fixed in formalin. Uteri from P females that appeared nongravid were opened and placed in 10% ammonium sulfide solution for detection of implantation sites. Any foci detected were considered early resorptions, and the data included in the mean calculations. Fixed tissue samples were paraffin-embedded, sectioned, and stained with hematoxylin- eosin. - Postmortem examinations (offspring):
- SACRIFICE
- All F1 offspring not selected for the 13-week study phase were euthanized and subjected to
necropsy on PND 22. These animals were subjected to postmortem examinations (macroscopic and/or microscopic examination).
GROSS NECROPSY
- All necropsied F1 animals were examined carefully for external abnormalities, including palpable masses, and were subjected to a full and detailed macroscopic examination of organs and tissues and the results recorded.
HISTOPATHOLOGY / ORGAN WEIGTHS
- Organs and tissues from F1 animals, were fixed in 10% neutral buffered formalin. Formalin was infused into the lungs via the trachea and into the urinary bladder. The eye (with) optic nerve, testes, and epididymides were fixed in a modified Davidson’s fixative. Target organs, gross lesions, and tissue masses with regional lymph nodes also were collected and fixed in formalin. Fixed tissue samples were paraffin-embedded, sectioned, and stained with haematoxylin- eosin. Routine histopathological examination of all organs/tissues was performed for F1 animals in the control and high-dose groups (10 animals/sex/group). Histopathological examination of target organs, gross lesions, and tissue masses (with regional lymph nodes) also was performed for F1 animals. - Statistics:
- Statistical analyses were conducted comparing each treated group to the control group for each sex and each endpoint. The results of all pair-wise comparisons were reported at the 0.05 and 0.01 significance levels
- Reproductive indices:
- Reproductive performance and parturition
- Offspring viability indices:
- Litter observations
- 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
- Food efficiency:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- A few macroscopic findings were noted in the glandular stomach in the low- and high-dose groups; not compound related.
- Histopathological findings: neoplastic:
- no effects observed
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- >= 1 other: percent in diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: highest dose tested
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- A statistically significant decrease in mean body weight in females at 0.25% on PND 21 was obserrved, but was considered not toxicologically meaningful.
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- >= 1 other: percent in diet
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: highest dose tested
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- NOAEL greater than or equal to 1% in diet.
The test item was without maternal toxicity or compound-related adverse effects on female reproduction and general growth and development of offspring at a maternal dietary level up to 1%, equivalent to a dose of 1655 mg/kg body weight (bw)/day. - Executive summary:
The test item was administered in the diet at dose levels of 0.25%, 0.5%, and 1.0% to groups of 26 male (during mating) and female (28 days prior to mating through weaning of the F1 generation) rats. Female rats and pups not selected for the 13-week post-weaning dietary study were sacrificed on PND 22. Reproductive parameters were evaluated. Feed consumption, body-weight gain, selected organ-weights, gross pathology and appropriate histopathology were also evaluated.
No biologically significant differences in body weight gain, food consumption, and food efficiency were noted. Also, no effects of the test item administration were observed at necropsy. A few macroscopic findings were noted in the glandular stomach in the low- and high-dose groups, but were mild in nature and showed no definitive compound-related toxic effects. No statistically or biologically significant effects on reproductive and fertility parameters or on parturition and litter parameters were observed between any of the test item and control groups. During the pre-weaning period, there were no observable differences with respect to the clinical signs exhibited by pups of the test item groups relative to the controls. All clinical signs were sporadic and incidental in nature with no relationship to test item administration. A statistically significant decrease in mean body weight was noted in females at 0.25% dose level on PND 21. Based on the lack of statistically significant changes in body weight at the higher dose groups (0.5% and 1.0%), this change was considered spurious in nature and not toxicologically meaningful. No statistically significant differences were observed between female groups.
The test item was without maternal toxicity or compound-related adverse effects on female reproduction and general growth and development of offspring at a maternal dietary level up to 1%, equivalent to a dose of 1655 mg/kg body weight (bw)/day. The NOAEL is greater than or equal to 1% of the test substance in the diet.
Reference
- A few macroscopic findings were noted in the glandular stomach in the low- and high-dose groups, but were mild in nature and showed no definitive compound-related toxic effects.
- A statistically significant decrease in mean body weight was noted in females at 0.25% dose level on PND 21. Based on the lack of statistically significant changes in body weight at the higher dose groups (0.5% and 1.0%), this change was considered spurious in nature and not toxicologically meaningful. No statistically significant differences were observed between female groups.
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 1 655 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Comparable to guideline with acceptable restrictions.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
No reproductive toxicity screening study with the test substance is available. An OECD 415 Guideline study in rats with L-fucose was used as a read across to fulfill the data gap for the test substance. The underlying hypothesis supporting read-across from L-Fucose to L-Rhamnose includes the following: (1) L-Fucose and L-Rhamnose are fully hydrolysed monosaccharide stereo isomers with the exception of one methyl group differing at one of four stereocenters. (2) L-Fucose and L-Rhamnose have similar physicochemical properties. (3) L-Fucose and L-Rhamnose share identical OECD QSAR Toolbox v3.4 alert profiles. (4) L-Fucose and L-Rhamnose share identical chemical descriptor profiles, based on descriptors calculated with ADMET Predictor7.2and OASIS TIMES v2.27.19. These same chemical descriptors are the constituent components of QSAR models in ADMET Predictor and OASIS Times. Therefore, the predictions for L-Fucose and L-Rhamnose for all endpoints assessed by ADMET Predictor and OASIS TIMES will be identical. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.
The test item was administered in the diet at dose levels of 0.25%, 0.5%, and 1.0% to groups of 26 male (during mating) and female (28 days prior to mating through weaning of the F1 generation) rats. Female rats and pups not selected for the 13-week post-weaning dietary study were sacrificed on PND 22. Reproductive parameters were evaluated. Feed consumption, body-weight gain, selected organ-weights, gross pathology and appropriate histopathology were also evaluated. The test item was without maternal toxicity or compound-related adverse effects on reproduction and general growth and development of offspring at a maternal dietary level up to 1%, equivalent to a dose of 1655 mg/kg body weight (bw)/day. The NOAEL is greater than or equal to 1% (1655 mg/kg) of the test substance in the diet.
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
No test substance-related adverse effects on reproductive outcomes were observed in a rat feeding study with the read-across chemical, L-fucose. No developmental data are available for the test substance. Therefore, the substance cannot be classified at this time for reproductive toxicity according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.
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.
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