Benzyl 4-hydroxybenzoate

Repeated dose toxicity: oral

Administrative data

Endpoint:

repeated dose toxicity: oral

Remarks:

combined repeated dose and reproduction / developmental screening

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

Test material information

Constituent 1

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 animal
TEST ANIMALS
- Source: Experimental Animal Tech Co. of Weitonglihua (Beijing, China).
- Age at study initiation: Immature SD rats (Post natal day :20)
- Weight at study initiation: 61.1 ± 7.9 to 68.5 ± 6.3g
- Fasting period before study: No data available
- Housing: two or three rats per stainless steel wire-mesh cage
- 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)

Vehicle:

peanut oil

Details on oral exposure:

Details on oral 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

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

3 days (PND 21 -24)

Frequency of treatment:

Daily

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

Positive control:

No data available

Examinations

Observations and examinations performed and frequency:

Observations and examinations performed & frequency
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

FOOD EFFICIENCY:
- 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 AND COMPOUND INTAKE (if drinking water study): 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:
Uterotrophic assay: Performed on PND 24 day, uterus of each rat was dissected. Each uterus was blotted, and the blotted weight was recorded.

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

No data available

Statistics:

One-way analysis of variance and Fisher’s least significant difference (LSD) method.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Mortality: All rats were scarified at PND 24 day after 24 hrs of last treated diet taken. Clinical signs: No data available

Mortality:

mortality observed, treatment-related

Description (incidence):

Mortality: All rats were scarified at PND 24 day after 24 hrs of last treated diet taken. Clinical signs: No data available

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

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

Uterus weight was increased of rats given 0.16 mg/kg/day or more of benzylparaben. The relative uterine weight was increased to 103%, 107%, 119%, 124%, 127%, 131%, and 136% that of rats in the control group.

Gross pathological findings:

effects observed, treatment-related

Description (incidence and severity):

Uterine weight was increased

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

other: LOED (Lowest observed Effective dose)

Effect level:

0.16 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: Blotted Uterus weight

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The endpoint for repeated dose toxicity test for benzylparaben (94-18-8) was found to be LOED at 0.16 mg/kg/day.

Executive summary:

Repeated dose 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 repeated dose toxicity test for benzylparaben (94-18-8) was found to be LOED at 0.16 mg/kg/day.