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EC number: 202-785-7 | CAS number: 99-76-3
- 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: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- received: 5. May 1998
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Well performed guideline-conform study with restricted reporting.
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 998
- Report date:
- 1998
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: OECD 440
- Deviations:
- yes
- Remarks:
- analysis of phytoestrogens in diet and daily body weight not reported, 5 animals/dose group
- Principles of method if other than guideline:
- n.a.
- GLP compliance:
- not specified
- Type of method:
- in vivo
Test material
- Reference substance name:
- Methyl 4-hydroxybenzoate
- EC Number:
- 202-785-7
- EC Name:
- Methyl 4-hydroxybenzoate
- Cas Number:
- 99-76-3
- Molecular formula:
- C8H8O3
- IUPAC Name:
- methyl 4-hydroxybenzoate
- Reference substance name:
- Methylparaben
- IUPAC Name:
- Methylparaben
- Details on test material:
- Supplier: Aldrich Chemical Company (Gilligham, Dorset, UK)
Puritiy: > 99%
Constituent 1
Constituent 2
Test animals
- Species:
- rat
- Strain:
- other: Alpk:AP
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Immature rats: 21-22 days old, 35-38 g; from Zeneca breeding unit (Alderley Park)
Ovariectomised rats: obtained from Zeneca breeding unit (Alderley Park). The ovariectomy was performed on 6 to 8 week old animals.They were maintained for 2 weeks after the operation, during which time daily vaginal smears were taken, and only noncycling animals were used for the uterotrophic assay.
Husbandry:
All animals were housed in wire mesh cages; solid bottoms were provided for immature animals. Temperature was controlled at 22+/-3°C, humidity was controlled at 30-70%, and a 12 h/12 h light dark cycle was maintained. Animals were weaned on R&M No. 3 (Special Diet Services Ltd., William Essex, UK) at postnatal Days 19-21 and maintained on R&M No. 1 (Special Diet Services Ltd.) from postnatal Day 21 omward. Diet and water were available ad libitum.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- arachis oil
- Details on exposure:
- Each experiment was accompanied by a vehicle control group (arachis oil) and a positive control group (17ß-Estradiol (0.4 mg/kg bw/d) by oral gavage or subcutaneous injection. Animals were dosed on 3 successive days with Methylparaben/17ß-Estradiol dissolved/suspended in Arachis oil. The maximum doses used were determined by turbidity of the dosing solutions and restriction of dosing volume.
- Analytical verification of doses or concentrations:
- not specified
- Details on analytical verification of doses or concentrations:
- no data
- Duration of treatment / exposure:
- 3 days
- Frequency of treatment:
- Daily
- Duration of test:
- Ovariectomised rats:
- Ovariectomy on 6-8 week old rats
- 2 weeks maintainance after operation (only noncycling females were used for assay)
- 3 days treatment, necropsy 24 h after last treatment
Immature rats:
- 24 h acclimatisation
- 3 days treatment, necropsy 24 h after last treatment
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
40 mg/kg bw/d
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
400 mg/kg bw/d
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
800 mg/kg bw/d
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
40 mg/kg bw/d
Basis:
other: subcutaneous
- Remarks:
- Doses / Concentrations:
80 mg/kg bw/d
Basis:
other: subcutaneous
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Negative control: Arachis oil
Positive control: 17ß-Estradiol
Animals were killed by an overdose of halothane 24 h after the final dose. Vaginal opening was recorded for immature animals at the time of death. Vaginal smears were also taken from ovariectomised animals at the time of death. Uteri were excised, trimmed free of fat, pierced, and blotted to remove excess fluid. The body of the uterus was cut just above its junction with the cervix and at the junction of the uterine horns with the ovaries. The uterus was then weighed (wet weight). Uterine dry weight was also determined by drying the uteri at 70°C for 24 h before reweighing. A quantitative estimation of vaginal cytology was performed by counting the number of fully cornified cells in at least 2 fields containing a total of at least 100 cells (x200 magnification). - Statistics:
- Variation within experiments for uterus wet and dry weights was determined by analysis of variance using the GLM procedure. Percentages of cornified cells were also considered by analysis of variance, following a double arcsine transformation (Freeman and Turkey, 1950). Differences from control values were assessd statistically using a two-sided Student´s t test based on the error mean square from the analysis of variance.
Results and discussion
Effect levels
- Dose descriptor:
- NOEL
- Effect level:
- 800 mg/kg bw/day (actual dose received)
- Sex:
- female
- Basis for effect level:
- other: no increase in uterus weights or premature vaginal opening
Observed effects
No increases in uterus weight
No premature vaginal opening
No increase in vaginal cornification
Any other information on results incl. tables
Table 1: The Activity of Methylparaben in the Immature Rat Uterotrophic Assay
Compound |
Dose/ |
Route |
Uterus weight/[mg] |
|
|
[mg/kg bw/d] |
|
Wet |
Dry |
|
|
|
|
|
Estradiol |
0.4 |
oral |
117.5±8.9* |
22.5±1.8* |
Arachis oil |
10 mL/kg bw/d |
oral |
33.8±5.9 |
6.4±0.9 |
Methylparaben |
40 |
oral |
34.5±3.2 |
6.8±0.7 |
Methylparaben |
400 |
oral |
33.3±5.3 |
6.3±0.9 |
Methylparaben |
800 |
oral |
31.0±4.3 |
6.2±0.7 |
Methylparaben |
40 |
subcutaneous |
33.5±6.6 |
6.8±1.1 |
Methylparaben |
80 |
subcutaneous |
32.8±1.5 |
6.6±0.3 |
|
|
|
|
|
* p<0.01
Applicant's summary and conclusion
- Conclusions:
- Methylparaben (orally as well as subcutaneously applied to immature/ovariectomised rats) was inactive in this uterotrophic assay at concentration up to 800 mg/kg bw/d (NOEL).
- Executive summary:
Methylparaben was administered to immature and ovariectomised rats assigned to 5 groups of 5 animals each at doses of 40, 400, 800 mg/kg bw/d (orally) and 40, 80 mg/kg bw/d (subcutaneously). 24 h after the last (third) administration, the rats were sacrificed, the weight of the uteri (wet and dry) was recorded and a quantitative estimation of the vaginal cytology was performed. There were no effects in any group. Based on the results of this assay the respective NOEL is > 800 mg/kg bw/d.
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