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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Toxicological information

Toxicity to reproduction

Currently viewing:

Administrative data

Endpoint:
fertility, other
Remarks:
based on test type (migrated information)
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:
The estrogenic effects of benzylparaben at low doses based on uterotrophic assay in immature SD rats
Author:
Ying Hu , Zhaobin Zhang , Libei Sun , Desheng Zhu , Qingchun Liu , Jian Jiao , Jun Li , Mingwen Qi
Year:
2013
Bibliographic source:
Food and Chemical Toxicology 53 (2013) 69–74

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as per mentioned below
Principles of method if other than guideline:
Study of estrogenic effects on the basis of uterotrophic assay in immature SD rats treated with benzylparaben.
GLP compliance:
no

Test material

Constituent 1
Chemical structure
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): Purity: >98%

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
Details on test animals and env. conditions
TEST ANIMALS
- Source: Experimental Animal Tech Co. Of Weitonglihua (Beijing, China).
- Age at study initiation: Immature SD rats (20th Post natal day rats)
- Weight at study initiation: 61.1 ± 7.9 to 68.5 ± 6.3 g
- Fasting period before study: No data available
- Housing: two or three rats per stainless steel wire-mesh cage
- Use of restrainers for preventing ingestion (if dermal): No data available
- Diet (e.g. ad libitum): basic diet (ad libitum)
- Water (e.g. ad libitum): sufficient drinking water (ad libitum)
- Acclimation period: No data available

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data available
- Humidity (%):No data available
- 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

Route of administration:
other: Oral (Intragastric administration)
Type of inhalation exposure (if applicable):
not specified
Vehicle:
peanut oil
Details on exposure:
Details on exposure
PREPARATION OF DOSING SOLUTIONS: No data available

DIET PREPARATION
- Rate of preparation of diet (frequency): No data available
- Mixing appropriate amounts with (Type of food): No data available
- Storage temperature of food: No data available

VEHICLE
- Justification for use and choice of vehicle (if other than water): No data available
- Concentration in vehicle: No data available
- Amount of vehicle (if gavage): No data available
- Lot/batch no. (if required): No data available
- Purity: No data available
Details on mating procedure:
- M/F ratio per cage: Not applicable
- Length of cohabitation: Not applicable
- Proof of pregnancy: [vaginal plug / sperm in vaginal smear] referred to as [day 0 / day 1] of pregnancy Not applicable
- After ... days of unsuccessful pairing replacement of first male by another male with proven fertility. Not applicable
- Further matings after two unsuccessful attempts: [no / yes (explain)] Not applicable
- After successful mating each pregnant female was caged (how): Not applicable
- Any other deviations from standard protocol: Not applicable
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
Not applicable
Duration of treatment / exposure:
3 days (PND 21-PND 24)
Frequency of treatment:
Daily
Details on study schedule:
No data available
Doses / concentrations
Remarks:
Doses / Concentrations:
0.16, 0.8, 4, 20, and 100 mg/kg bw/day for experiment 1 0.0064 and 0.032 mg/kg bw/ day for experiment 2
Basis:
no data
No. of animals per sex per dose:
14 /dose
Control animals:
yes
Details on study design:
No data available

Examinations

Parental animals: Observations and examinations:
Parental animals observation and examinations
CAGE SIDE OBSERVATIONS: Yes
- 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

BODY WEIGHT: Yes
- Time schedule for examinations:Daily

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data available
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No data available

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data available
- Time schedule for examinations: No data available
Oestrous cyclicity (parental animals):
No data available
Sperm parameters (parental animals):
No data available
Litter observations:
No data available
Postmortem examinations (parental animals):
No data available
Postmortem examinations (offspring):
No data available
Statistics:
One-way analysis of variance and Fisher’s least significant difference (LSD) method.
Reproductive indices:
No data available
Offspring viability indices:
No data available

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P0)

Key result
Dose descriptor:
other: LOED (Lowest observed Effective dose)
Effect level:
0.16 mg/kg bw/day
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Blotted Uterus weight
Remarks on result:
other: no other details available

Target system / organ toxicity (P0)

Critical effects observed:
not specified
Organ:
other: not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: P1 (second parental generation)

General toxicity (P1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality:
not specified
Body weight and weight changes:
not specified
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
Immunological findings:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Neuropathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Other effects:
not specified

Reproductive function / performance (P1)

Reproductive function: oestrous cycle:
not specified
Reproductive function: sperm measures:
not specified
Reproductive performance:
not specified

Effect levels (P1)

Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (P1)

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified

Effect levels (F1)

Dose descriptor:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F1)

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Results: F2 generation

General toxicity (F2)

Clinical signs:
not specified
Dermal irritation (if dermal study):
not specified
Mortality / viability:
not specified
Body weight and weight changes:
not specified
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
Sexual maturation:
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
not specified
Other effects:
not specified

Developmental neurotoxicity (F2)

Behaviour (functional findings):
not specified

Developmental immunotoxicity (F2)

Developmental immunotoxicity:
not specified

Effect levels (F2)

Dose descriptor:
other: not specified
Generation:
other: not specified
Based on:
not specified
Sex:
not specified
Remarks on result:
other: not specified

Target system / organ toxicity (F2)

Critical effects observed:
not specified
Treatment related:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Overall reproductive toxicity

Reproductive effects observed:
not specified
Treatment related:
not specified
Relation to other toxic effects:
not specified
Dose response relationship:
not specified
Relevant for humans:
not specified

Applicant's summary and conclusion

Conclusions:
The endpoint for reproduction toxicity test for benzylparaben (94-18-8) was found to be LOED at 0.16 mg/kg/day.
Executive summary:

Reproduction toxicity test was performed on SD rats from PND 21 to PND 24 days were treated with benzylparaben. The chemical was given by Intragastric route dissolve in peanut oil. On 24 PND days the rats were scarified by chloroform anesthesia 24 h after the final treatment. The uterus of all rats were dissected and blotted to study the uterotrophic effect of benzylparaben. Relative uterine weight was calculated for each animal.

After experiment it was found that the relative uterine weight was increased to 103%, 107%, 119%, 124%, 127%, 131%, and 136% that of rats in the control group.

Therefore,the endpoint for reproduction toxicity test for benzylparaben (94-18-8) was found to be LOED at 0.16 mg/kg/day.