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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 200-186-5 | CAS number: 53-86-1
- 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:
- toxicity to reproduction
- Remarks:
- other: (female fertility study)
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Reliability:
- 4 (not assignable)
Data source
Reference
- Reference Type:
- publication
- Title:
- Collaborative work on evaluation of ovarian toxicity - 12) Effects of 2- or 4-week repeated dose studies and fertility study of indomethacin in female rats
- Author:
- Tsubota K et al.
- Year:
- 2 009
- Bibliographic source:
- Journal of Toxicological Science (Special Issue I): SP 129 - SP 136
Materials and methods
- Principles of method if other than guideline:
- Ten females/group were treated daily by gavage with indomethacin, for 2 weeks before mating, during mating with untreated males and until day 7 of pregnancy. Timing of estrus phase was determined during the 2-week premating treatment phase. Necropsies were performed on day 14 of gestation and females examined for reproductive parameters.
Test material
- Reference substance name:
- Indometacin
- EC Number:
- 200-186-5
- EC Name:
- Indometacin
- Cas Number:
- 53-86-1
- Molecular formula:
- C19H16ClNO4
- IUPAC Name:
- 2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1H-indol-3-yl]acetic acid
- Details on test material:
- supplied by Sigma-Aldrich, St. Louis, MO, USA; suspended in 0.5% methylcellulose suspension
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: (Crl:CD(Sprague-Dawley)
- Sex:
- female
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: (0.5% methylcellulose solution; Metlose(R) SM-400)
- Duration of treatment / exposure:
- females were treated 2 weeks before the mating period, through mating and until day 7 of pregnancy
- Frequency of treatment:
- once daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0 - 0.4 - 1.3 - 4 mg/kg bw
Basis:
nominal conc.
- No. of animals per sex per dose:
- 10 females/dose
- Control animals:
- yes, concurrent vehicle
Results and discussion
Results: P0 (first parental generation)
Effect levels (P0)
- Dose descriptor:
- NOAEL
- Effect level:
- 1.3 mg/kg bw/day (nominal)
- Sex:
- female
- Basis for effect level:
- other: systemic and reproductive effects
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
At 4 mg/kg females showed clinical signs, impaired body weight development, mortality and gross pathological lesions (gastrointestinal ulcers, peritonitis). Three animals of the 4 mg/kg group showed prolonged diestrus (> 3 days) most probably as the result of their poor condition exacerbated by gastrointestinal damage. The reproductive outcome at 0.4 mg/kg and 1.3 mg/kg was not significantly different from those in the control. Numeric values were not analyzed at the 4 mg/kg dose level due to high maternal mortality.
Dose (mg/kg bw/day) |
0 |
0.4 |
1.3 |
4 |
Finding in Females |
|
|
|
|
Clinical signs |
- |
- |
- |
decreased spontaneous motility, moist fur around urethal orifice, prone position and soiled fur aorund the nose |
No. that died/sacrificed moribund |
- |
- |
- |
8 (six during the premating period and 2 during mating) |
BW gain (g) (day 1-15) |
19 |
20 |
14 |
5** |
Mean No. Estrus phase/15 days |
3.7 |
3.8 |
3.7 |
3.8 |
Irregular estrus cycle (diestrus persists for 3 days or longer) |
0 |
1 |
2 |
3 |
No. of animals mated |
10 |
10 |
10 |
3 |
No. of animals copulated (inseminated) |
10 |
10 |
10 |
3 |
No. of pregnant animals |
10 |
10 |
10 |
2 |
Necropsy findings |
- |
- |
- |
Intestinal ulcers, peritonitis, adhesion of various celiac organs |
Mean no. of Corpora lutea |
14.9 |
15.8 |
14.4 |
12.5 |
Mean no. of implantations |
14.0 |
14.6 |
13.4 |
10.0 |
Mean % preimplantation loss |
5.5 |
7.1 |
7.2 |
19.8 |
Mean no. live embryos |
13.1 |
13.9 |
12.4 |
9.5 |
Mean no. dead embyos |
0.9 |
0.7 |
1.0 |
0.5 |
Mean % postimplantation loss |
6.5 |
4.9 |
7.4 |
5.6 |
|
|
|
|
|
BW: body weight; ** : statistically significant difference to control with p < 0.01 |
Applicant's summary and conclusion
- Executive summary:
Ten females/group were treated daily by gavage with indomethacin, for 2 weeks before mating, during mating with untreated males and until day 7 of pregnancy with doses of 0, 0.4, 1.3 and 4 mg/kg bw.. Timing of estrus phase was determined during the 2-week premating treatment phase. Necropsies were performed on day 14 of gestation and females examined for reproductive parameters.
At 4 mg/kg females showed clinical signs, impaired body weight development, mortality and gross pathological lesions (gastrointestinal ulcers, peritonitis). Three animals of the 4 mg/kg group showed prolonged diestrus (> 3 days) most probably as the result of their poor general condition exacerbated by gastrointestinal damage. The reproductive outcome at 0.4 mg/kg and 1.3 mg/kg was not significantly different from those in the control. Numeric values were not analyzed at the 4 mg/kg dose level due to high maternal mortality. The NOAEL was established in this study at 1.3 mg/kg bw/day.
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.