Benzoic acid, 4-hydroxy-, C18-22-alkyl esters

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

26 Jan - 20 Jul 1972

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Basic data given. Publication is written in Japanese.

Data source

Reference

Reference Type:

publication

Title:

Synergistic toxicity of official permissible preservative food additives

Author:

Sado, I.

Year:

1973

Bibliographic source:

Japanese Journal of Hygiene 28:463–476.

Materials and methods

Principles of method if other than guideline:

The study was conducted before appropriate test guidelines and GLP were developed. The test item was administered orally to rats in the diet for 25 weeks. Clinical signs, food consumption and body weights and blood parameters were observed. At study termination, gross necropsy and histopathological examinations were conducted.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Ethyl 4-hydroxybenzoate

EC Number:

204-399-4

EC Name:

Ethyl 4-hydroxybenzoate

Cas Number:

120-47-8

IUPAC Name:

ethyl 4-hydroxybenzoate

Details on test material:

- Name of test material (as cited in study report): Ethyl p-hydroxybenzoate
- Analytical purity: not available

Test animals

Species:

rat

Strain:

other: SD-JCL

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:
- Age at study initiation: 5 weeks
- Diet: CE-2, ad libtum
- Water: ad libtum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1 °C
- Humidity (%): 50 ± 5%

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- Mixing appropriate amounts with (Type of food): 0.2, 1, 2%

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

25 weeks

Frequency of treatment:

daily

Doses / concentrations

Doses / concentrations 1

Remarks:

Doses / Concentrations:
0.2, 1 and 2%
Basis:
other:

Doses / concentrations 2

Remarks:

Doses / Concentrations:
120, 600, and 1200 mg/kg bw/day
Basis:
other: calculated based on 50 - 60 g/kg bw day food intake

No. of animals per sex per dose:

6, 5 and 5 males in 2%, 1% and 0.2% group
5 females in each group

Control animals:

yes, plain diet

Details on study design:

- Dose selection rationale: based on LD50 in mice

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: once a week

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: Yes
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No

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: Yes

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: after last administration
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all surviving animals
- Examined parameters: RBC, Hb, Ht, WBC, WBCP

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: after last administration
- Animals fasted: No data
- How many animals: all surviving animals
- Examined parameters: GOT and GPT, alkaliphosphate, cholinesterase, protein, A/G ratio, total chlesterol, blood sugar

URINALYSIS: Yes
- Time schedule for collection of urine: after last administration
- Metabolism cages used for collection of urine: No
- Animals fasted: No data
- Examined parameters: protein, sugar

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes: heart, lung, liver, spleen, kidney and other main organs

HISTOPATHOLOGY: Yes: heart, lung, liver, spleen, kidney

Statistics:

t-test or chi-square test

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Significant higher body-weight was observed in males in 0.2% group. Significant lower body weight was observed in males in 1 and 2% group.

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

no effects observed

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 1 200 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: corresponding to 2% test material in diet, calculation based 50 - 60 g/kg bw day food intake

Target system / organ toxicity

Critical effects observed:

not specified