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EC number: 472-110-0 | CAS number: 71868-15-0
- 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
![](https://echa.europa.eu/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Endpoint summary
Administrative data
Key value for chemical safety assessment
- Toxic effect type:
- dose-dependent
Effects on fertility
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- From January 28, 2021 to May 31, 2021
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
- Justification for study design:
- The dose levels were selected by the Sponsor in consultation with the Study Director, based on the results from an OECD 407 repeated dose 28-day oral toxicity study performed in another laboratory and a Dose Range Finding (DRF) study performed at the Test Facility with the aim of inducing toxic effects but no death or suffering at the highest dose, and to obtain a No Adverse Effect Dose Level (NOAEL) at the lowest dose.
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- Species and strain: Han:WIST rats
Source: Toxi-Coop Zrt., H-1122 Budapest, Magyar Jakobinusok tere 4B
Hygienic level at supplier: SPF
Hygienic level during the study: Standard housing conditions
Sex: Male and female. The females were nulliparous and non-pregnant at the start of the study.
Age of animals: Young adult rats, approximately 12 weeks old at start of dosing and 14 weeks old at mating.
Body weight range: Males: 372 – 431 g, females: 231 – 266 g; did not exceed
± 20 % of the mean weight for each sex at onset of dosing.
Acclimation period: 12 days - Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animal health: Only healthy animals were used for the test. The health status was certified by the Veterinarian.
Housing: The animals were group-housed, up to 2 animals of the same sex/cage, with the exception of the mating and gestation/delivery/lactation period, when they were paired or individually housed (with pups), respectively.
Cage type: T3H polycarbonate
Bedding and nesting: “SAFE 3/4-S-FASERN” certified wooden chips (batch number: 03027201125, expiry date: 11 November 2023) produced by J. Rettenmaier & Söhne GmbH & Co.KG (Holzmühle 1, D-73494 Rosenberg, Germany) and “Sizzle pet” nest material (batch number: 491607, expiry date: 05 August 2023) produced by LBS (Serving Biotechnology) Ltd. (Unit 20, Gatwick Business Park, Kennel Lane, Hookwood, Surrey, RH6 0AH, United Kingdom) were available to animals during the study. Copies of the Certificates of Analyses are archived with the raw data.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 19 – 24 °C (target range 22 ± 3 °C)
Relative humidity: 31 – 57 % (target range 30-70 %)
Ventilation: 15-20 air exchanges/hour
Housing/Enrichment: Group housing allowed social interaction and the deep wood sawdust bedding allowed digging and other normal rodent activities. Nest building material allowed normal nesting behaviour. Fresh bedding was provided for the animals as frequently as appropriate/practical, but at least twice weekly. - Route of administration:
- oral: gavage
- Vehicle:
- other: Methylcellulosum and aqua purificata (distilled water)
- Details on exposure:
- The test item was administered to the animals daily on a 7 days/week basis, by oral gavage using a tipped gavage needle attached to a syringe. A constant volume of 5 mL/kg bw was administered to all animals. The actual volume to be administered was calculated and adjusted based on each animal’s most recent body weight.
Dosing of both sexes began after 12 days acclimatisation and pre-exposure period (14 days), and it was performed 2 weeks before mating, during the mating, and was continued up to and including the day before the necropsy. - Details on mating procedure:
- Mating began after the animals have attained full sexual maturity, 2 weeks after the initiation of dosing, with one female and one male (1:1 mating) in a single cage. Females remained with the same male until copulation occurred. A vaginal smear was prepared daily during the mating period and stained with 1 % aqueous methylene blue solution. The smear was examined with a light microscope. The presence of vaginal plug or sperm in the vaginal smear was considered as evidence of copulation (Day 0 of pregnancy). Sperm positive females were caged individually.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Concentration and homogeneity of the dosing formulations were determined three times during the study.
Based on the results, all test item formulations were shown to be homogeneous and they were found to be in the range of 92 to 101% of nominal concentrations. No test item was detected in the negative (vehicle) control sample. Based on these results, formulations were considered suitable for the study purposes. - Duration of treatment / exposure:
- Parental males were dosed for 28 days (14 days pre-mating and 14 days mating/post-mating period).
Parental females were dosed for 14 days pre-mating, for up to 4 days during mating period, through gestation and up to and including the day before necropsy (13 days post-partum dosing). - Frequency of treatment:
- Daily on a 7 days/week basis.
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 10 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 30 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 100 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 12/sex/dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Male and female Wistar rats were treated for 2 weeks pre-mating and then during the mating/post-mating periods. This was 28 days in total for males. Females were treated throughout gestation and up to and including postpartum/lactation Day PPD13.
Parameters measured during the study included signs of morbidity and mortality twice daily, daily general observation or weekly detailed observation of clinical signs, weekly body weight and food consumption. In addition, the reproductive performance, pregnancy, parturition and postpartum/lactation period were monitored in the adult animals, and viability, clinical signs and development were evaluated in their F1 offsprings until PND13. At termination, necropsy with macroscopic examination was performed. Selected organs were weighed and/or preserved in appropriate fixatives from the adult animals. A detailed histological examination was performed on the selected list of retained organs in the Control and High dose groups. The thyroxine (T4) levels in the Day 13 pups and adult males were also assessed. - Parental animals: Observations and examinations:
- At 100 mg/kg bw clinical symptoms were observed such as hunched back (3/12), piloerection (5/12) and slight decreased activity (1/12) in males and hunched back (2/12) in females.
At the high dose level of 100 mg/kg bw/day, body weight loss were observed both in male and female groups. - Oestrous cyclicity (parental animals):
- No effect of test item on oestrus cycles was noted.
- Litter observations:
- There were no test item related differences in the offsprings body weights, anogenital distance or nipple retention and thyroid gland or T4 hormone levels.
- Postmortem examinations (parental animals):
- No treatment related macroscopic findings were noted at necropsy.
No test item related microscopic changes were observed in the investigated reproductive and other organs of the animals. - Reproductive indices:
- There were no differences between the control and test item dosed groups with regard to reproductive ability, mating or gestation indices that could be ascribed to the test item administration.
- Offspring viability indices:
- There was no test item-related effect on mortality or survival of the pups.
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Treatment at 100 mg/kg bw was associated with clinical symptoms such as hunched back (3/12), piloerection (5/12) and slight decreased activity (1/12) in males and hunched back (2/12) in females.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- At the high dose level of 100 mg/kg bw/day, statistically significant decrease of body weight were observed, both in male and female groups.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- Test item related reduction of mean food consumption was observed during the first seven days of treatment in the high dose groups (p <0.05 for males and p < 0.01 for females).
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not examined
- 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:
- 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive performance
- Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 30 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- Key result
- Critical effects observed:
- no
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Anogenital distance (AGD):
- no effects observed
- Nipple retention in male pups:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
- Behaviour (functional findings):
- not examined
- Developmental immunotoxicity:
- not examined
- Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 100 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- other: Development
- Key result
- Critical effects observed:
- no
- Key result
- Reproductive effects observed:
- no
- Conclusions:
- Under the study conditions, the parental systemic toxicity NOAEL was determined to be 30 mg/kg bw/day and the reproductive/developmental toxicity NOAEL was 100 mg/kg/ kg bw/day. The NOAEL for pup development and survival was 100 mg/kg bw/day.
- Executive summary:
A screening study was conducted to determine the reproductive/developmental toxicity of the test substance according to OECD Guideline 421, in compliance with GLP. Parental male rats were exposed to the test substance once daily by oral gavage for 28 days (14 days pre-mating and 14 days mating/post-mating). Parental female rats were exposed daily for 14 days pre-mating, for up to 4 days during the mating period, through gestation and up to and including the day before necropsy (13 days post-partum). Test doses were 0, 10, 30 and 100 mg/kg bw/day. Accuracy and homogeneity of formulations were demonstrated by analyses.Treatment related clinical signs noted at 100 mg/kg bw/day consisted of hunched back (3/12), piloerection (5/12) and slight decreased activity (1/12) in males and hunched back (2/12) in females. No test substance related effect on oestrus cycle of parental females and in the reproductive parameters during mating and gestation, delivery and post-partum/lactation period until post=partum Day14 was noted.There were no adverse effects on F1 offspring viability, clinical signs, physical or sexual development. Under the study conditions, the parental systemic toxicity NOAEL was determined to be 30 mg/kg bw/day and the reproductive/developmental toxicity NOAEL was 100 mg/kg/ kg bw/day. The NOAEL for pup development and survival was 100 mg/kg bw/day (Rigó Kiss, 2021).
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 100 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
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 screening study was conducted to determine the reproductive/developmental toxicity of the test substance according to OECD Guideline 421, in compliance with GLP. Parental male rats were exposed to the test substance once daily by oral gavage for 28 days (14 days pre-mating and 14 days mating/post-mating). Parental females rats were exposed daily for 14 days pre-mating, for up to 4 days during the mating period, through gestation and up to and including the day before necropsy (13 days post-partum). Test doses were 0, 10, 30 and 100 mg/kg bw/day. Accuracy and homogeneity of formulations were demonstrated by analyses.Treatment-related clinical signs noted at 100 mg/kg bw/day consisted of hunched back (3/12), piloerection (5/12) and slight decreased activity (1/12) in males and hunched back (2/12) in females. No test substance related effect on oestrus cycle of parental females and in the reproductive parameters during mating and gestation, delivery and post-partum/lactation period until post partum Day14 was noted.There were no adverse effects on F1 offspring viability, clinical signs, physical or sexual development. Under the study conditions, the parental systemic toxicity NOAEL was determined to be 30 mg/kg bw/day and the reproductive/developmental toxicity NOAEL was 100 mg/kg/ kg bw/day. The NOAEL for pup development and survival was 100 mg/kg bw/day (Rigó Kiss, 2021).
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
Based on the result of a reproductive/developmental screening study (OECD Guideline 421), the test substance does not warrant classification for this endpoint according to EU CLP criteria (Regulation 1272/2008/ EC).
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.
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