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EC number: 202-311-9 | CAS number: 94-18-8
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- short-term repeated dose toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Data is from peer reviewed journal
Data source
Reference
- Reference Type:
- publication
- Title:
- Oestrogenic Activity of Benzylparaben
- Author:
- P. D. Darbre, J. R. Byford, L. E. Shaw,S. Hall,N. G. Coldham,G. S. Pope and M. J. Sauer
- Year:
- 2 003
- Bibliographic source:
- J. Appl. Toxicol. 23, 43–51 (2003)
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- other: as per mentioned below
- Principles of method if other than guideline:
- Subacute Study of oestrogenic activity of benzylparaben on immature mouse uterine weight.
- GLP compliance:
- no
Test material
- Reference substance name:
- Benzyl 4-hydroxybenzoate
- EC Number:
- 202-311-9
- EC Name:
- Benzyl 4-hydroxybenzoate
- Cas Number:
- 94-18-8
- Molecular formula:
- C14H12O3
- IUPAC Name:
- benzyl 4-hydroxybenzoate
- Details on test material:
- - Name of test material (as cited in study report): Benzylparaben (Synonyms of Benzoic acid, 4-hydroxy-, phenyl methyl ester)
- Molecular formula (if other than submission substance): C14-H12-O3
- Molecular weight (if other than submission substance): 228.2458 g/mol
- Substance type: Organic
- Physical state: Solid
- Impurities (identity and concentrations): No data available
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- Details on test animal
TEST ANIMALS
- Source: Charles River, Kent, UK
- Age at study initiation: 18 days
- Weight at study initiation: No data available
- Fasting period before study: No data available
- Housing: Animals were housed in a cage of 450 mm × 280 mm × 130 mm
(length × depth × height) 7 animals per group.
- Diet (e.g. ad libitum): Standard diet in pellet form (Lillico RM1(P)), ad libitum.
- Water (e.g. ad libitum): No data available
- Acclimation period: 2 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 1 °C
- Humidity (%): 55 ± 5%
- Air changes (per hr): No data available
- Photoperiod (hrs dark / hrs light): No data available
IN-LIFE DATES: From: To: No data available
Administration / exposure
- Type of coverage:
- open
- Vehicle:
- ethanol
- Details on exposure:
- Details on dermal exposure
PREPARATION OF DOSING SOLUTIONS: Benzylparaben were disolved in 0.5 ml of ethanol
TEST SITE
- Area of exposure: Dorsal skin
- % coverage: No data available
- Type of wrap if used: No data available
- Time intervals for shavings or clipplings: No data available
REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data available
- Time after start of exposure: No data available
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0, 3.3, 10, 33 or 100 mg/ kg bw/day
- Concentration (if solution): No data available
- Constant volume or concentration used: yes
- For solids, paste formed: No
VEHICLE
- Justification for use and choice of vehicle (if other than water): Benzylparaben is soluble in ethanol
- Amount(s) applied (volume or weight with unit): 0, 3.3, 10, 33 or 100 mg/ kg bw/day
- Concentration (if solution): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available - Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- 3 days
- Frequency of treatment:
- Once in a day
Doses / concentrations
- Remarks:
- Doses / Concentrations:
3.3, 10, 33 or 100 mg of benzylparaben, 10, 25, 50, 100, 200, 1000, 5000, 25 000 or 100 000 ng of 17β-oestradiol.
Basis:
no data
- No. of animals per sex per dose:
- No data available
- Control animals:
- yes
- Details on study design:
- No data available
- Positive control:
- No data available
Examinations
- Observations and examinations performed and frequency:
- Observations and examinations performed & frequency
CAGE SIDE OBSERVATIONS: No data available
- Time schedule: No data available
- Cage side observations checked in table [No.?] were included. No data available
DETAILED CLINICAL OBSERVATIONS: No data available
- Time schedule: No data available
DERMAL IRRITATION (if dermal study): No data available
- Time schedule for examinations: No data available
BODY WEIGHT: Yes
- Time schedule for examinations: At termination of study
FOOD CONSUMPTION: No data available
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
FOOD EFFICIENCY: No data available
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data available
WATER CONSUMPTION: No data available
- Time schedule for examinations: No data available
OPHTHALMOSCOPIC EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
HAEMATOLOGY: No data available
- Time schedule for collection of blood: No data available
- Anaesthetic used for blood collection: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
CLINICAL CHEMISTRY: No data available
- Time schedule for collection of blood: No data available
- Animals fasted: No data available
- How many animals: No data available
- Parameters checked in table [No.?] were examined. No data available
URINALYSIS: No data available
- Time schedule for collection of urine: No data available
- Metabolism cages used for collection of urine: No data available
- Animals fasted: No data available
- Parameters checked in table [No.?] were examined. No data available
NEUROBEHAVIOURAL EXAMINATION: No data available
- Time schedule for examinations: No data available
- Dose groups that were examined: No data available
- Battery of functions tested: sensory activity / grip strength / motor activity / other: No data available
OTHER:
Organ weight: Yes
Uterus weight was weighted. - Sacrifice and pathology:
- GROSS PATHOLOGY: No data available
HISTOPATHOLOGY: No data available - Other examinations:
- No data available
- Statistics:
- The P values were calculated using a two-tailed two-sample Student’s t -test assuming unequal variance, within the MS Excel 2000 software package.
Results and discussion
Results of examinations
- Clinical signs:
- not specified
- Dermal irritation:
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Gross pathological findings:
- not specified
- Histopathological findings: non-neoplastic:
- not specified
- Histopathological findings: neoplastic:
- not specified
- Details on results:
- Clinical signs and mortality:No data available
Dermal Irritation: No data available
Body weight and weight gain: No effects on body weight and body weight gain were observed in all the treated mice as compared to control.
Food consumption and compound intake: No data available
Food efficiency: No data available
Water consumption and compound intake: No data available
Opthalmoscopic examination No data available
Haematology No data available
Clinical chemistry: No data available
Urinanalysis: No data available
Neurobehaviour: No data available
Organ weights When treated with 33 and 100 mg/ kg bw/day, dose-dependent significant increase in absolute and relative Uterus weight was observed as compared to control.
Gross pathology: No data available
Histopathology: No data available
Details on results
Two studies were conducted with same concentration
The results were show that benzylparaben can have weak uterotrophic activity when administered topically in ethanol to immature mice.
Effect levels
open allclose all
- Dose descriptor:
- LOAEL
- Effect level:
- 33 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: Effect on organ weight
- Dose descriptor:
- NOAEL
- Effect level:
- 10 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- female
- Basis for effect level:
- other: No adverse effect on body weight and organ weight
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
Effect of topical administration of benzylparaben on uterine weight in immature female CD1 mice
|
Treatment |
Uterine weight (mg) |
P value vs control |
Body weight (g) |
Uterine wt. / body wt. |
P value vs control |
Study 1 |
Control |
19.67 ± 0.83 |
|
13.22 ± 0.31 |
1.49 ± 0.06 |
|
|
17β-E 100 ng |
97.57 ± 6.03 |
<0.001 |
15.00 ± 0.66 |
6.51 ± 0.30 |
<0.001 |
|
17β-E 1000 ng |
99.71 ± 3.83 |
<0.001 |
15.92 ± 0.29 |
6.28 ± 0.27 |
<0.001 |
|
17β-E 5000 ng |
80.14 ± 3.56 |
<0.001 |
14.33 ± 0.37 |
5.59 ± 0.19 |
<0.001 |
|
17β-E 25 000 ng |
85.86 ± 4.67 |
<0.001 |
14.96 ± 0.20 |
5.74 ± 0.32 |
<0.001 |
|
17β-E 100000 ng |
89.14 ± 3.42 |
<0.001 |
14.39 ± 0.39 |
6.20 ± 0.19 |
<0.001 |
|
BenzPara 3.3 mg |
19.00 ± 1.35 |
0.682 |
13.55 ± 0.52 |
1.40 ± 0.07 |
0.329 |
|
BenzPara 10 mg |
24.14 ± 2.76 |
0.165 |
14.03 ± 0.43 |
1.71 ± 0.16 |
0.239 |
|
BenzPara 33 mg |
24.00 ± 1.84 |
0.064 |
13.16 ± 0.48 |
1.81 ± 0.08 |
0.008 |
|
BenzPara 100 mg |
31.71 ± 2.04 |
<0.001 |
13.64 ± 0.24 |
2.33 ± 0.16 |
0.002 |
Study 2 |
Control |
20.75 ± 2.53 |
|
12.19 ± 0.63 |
1.67 ± 0.13 |
|
|
17β-E 10 ng |
30.57 ± 1.74 |
0.008 |
14.25 ± 0.40 |
2.16 ± 0.14 |
0.023 |
|
17β-E 25 ng |
47.71 ± 1.51 |
<0.001 |
12.62 ± 0.53 |
3.81 ± 0.16 |
<0.001 |
|
17β-E 50 ng |
84.29 ± 4.98 |
<0.001 |
15.30 ± 0.61 |
5.52 ± 0.30 |
<0.001 |
|
17β-E 100 ng |
101.29 ± 3.46 |
<0.001 |
14.98 ± 0.35 |
6.77 ± 0.19 |
<0.001 |
|
17β-E 200 ng |
101.14 ± 5.43 |
<0.001 |
15.53 ± 0.42 |
6.51 ± 0.26 |
<0.001 |
|
BenzPara 3.3 mg |
28.29 ± 4.01 |
0.143 |
13.88 ± 0.35 |
2.01 ± 0.26 |
0.259 |
|
BenzPara 10 mg |
36.71 ± 6.19 |
0.044 |
14.50 ± 0.44 |
2.49 ± 0.34 |
0.056 |
|
BenzPara 33 mg |
30.86 ± 2.24 |
0.010 |
13.80 ± 0.72 |
2.23 ± 0.08 |
0.003 |
|
BenzPara 100 mg |
24.00 ± 1.68 |
0.306 |
14.01 ± 0.48 |
1.71 ± 0.10 |
0.798 |
Topical application of 0.5 ml of ethanol alone (control) or containing the stated close of oestradiol (E) or benzylparaben (BenzPara). Results are given as the mean ± SEM; p values are a two-tailed two-sample t -test assuming unequal variances.
Applicant's summary and conclusion
- Conclusions:
- NOAEL was considered to be 10 mg/kg bw/day and LOAEL was 33 mg/kg bw/day when CD1 female mice were treated with benzylparaben
- Executive summary:
In a Subacute repeated dose dermal toxicity study, CD1 female mice were treated with benzylparaben in the concentration of 0, 3.3, 10, 33 or 100 mg/ kg bw/day in 0.5 ml ethanol by applying on dorsal skin. No effects on body weight and body weight gain were observed in all the treated mice as compared to control. In addition, dose-dependent significant increases in absolute and relative Uterus weight wereobserved at 33 and 100 mg/kg bw/day treated female mice in both the studies as compared to control. Therefore, NOAEL was considered to be 10 mg/kg bw/day and LOAEL was 33 mg/kg bw/day when CD1 female mice were treated with benzylparaben dermally for 3 days.
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