4-hydroxybenzoic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2008-11-21 to 2009-01-13

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: according to OECD guideline 423 performed under GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-hydroxybenzoic acid

EC Number:

202-804-9

EC Name:

4-hydroxybenzoic acid

Cas Number:

99-96-7

Molecular formula:

C7H6O3

IUPAC Name:

4-hydroxybenzoic acid

Details on test material:

Sponsors Batch No.: 08/1000/10,1-20
production date: 20.10.2008
purity: 99,94%
colour: white
form: powder
storage: protected from light and moisture at room temperature
CAS: 99-96-7
name of testitem (Sponsor's identification): p-Hydroxybenzoesäure
Expiry date: October 2011

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
group 1: one female rat
group 2: six female rats, tested in two groups of three rats
- Source: Elevage JANVIER (53940 Le Genest St Isle - France)
-The rats were eight weeks old, weighed between 178-212g and were housed according to guideline conditions.
- Acclimation period: at least 5 days

Their body weight was determined on day 0, 2, 7 and 14 of the examination procedure. Observations on behavior and mortality were done every day
a systematic examination was carried out on day 14. Except of day one on which food access was allowed 4 hours after test item administration,
Food and drinking water was accessible freely throughout the whole period.
A periodic cycle of continuous light (12 hours) and dark (12 hours ) was guarenteed and a temperature between 19 and 25°C.
Humidity was 30-70 % rel Humidity. The animals were kept in groups of three animals in a clear polycarbonate cage, which was filled with sawdust on the bottom, which was cleaned at least twice a week.

Administration / exposure

Route of administration:

other: syringe and oral administration

Vehicle:

DMSO

Details on oral exposure:

The test item was dissolved in dimethyl sulfoxide (DMSO) and the respective doses were administered by gavage in a volume of 10ml/kg b.w.

Doses:

group1: 5000 mg/kg b.w.
group2: 2000 mg/kg b.w.

No. of animals per sex per dose:

1 female rat at 5000 mg/kg b.w.
6 female animals at 2000 mg/kg b.w. in 2 groups with 3 animals

Control animals:

other: Observations were compared to control data. It is not clearly stated if control animals were observed simultaneously besides treatments.

Details on study design:

one pre-test with one female using 5000 mg/kg. b.w. as dose finding
study then with two groups of three female rats using 2000 mg/kg b.w.

Statistics:

not applicable, results and findings for each animal noted

Results and discussion

Preliminary study:

At 5000 mg/kg b.w. the rat died 2h 45min after administration. It was noted: thickening of the corpus , thinning of the forestomach, white particles in the stomach, grey-brown adherences in stomach , duodenum and jejunum

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

5 000 mg/kg bw

Remarks on result:

other: pretest: the female rat died ca. 3h after the oral administration

Effect levels 2

Key result

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

>= 2 000 mg/kg bw

Remarks on result:

other: 2 groups of 3 female rats, no signs of toxicity

Mortality:

no mortality at 2000 mg/kg b.w.

Clinical signs:

other: no clinical signs at 2000 mg/kg b.w.

Gross pathology:

no abnormal findings at 2000 mg/kg b.w.

Other findings:

no macroscopically observable findings at 2000 mg/kg b.w.

Any other information on results incl. tables

In an acute oral dose-range finding toxicity study 1 female Sprague Dawley rat wasgiven a single oral dose of 4 -HBA of 5000  mg/kg bw. in 10 ml/kg bw. DMSO. Death was observed within 3 hours after administration.

In the following main study 2 groups of 3 female Sprague Dawley rats were given a single oral dose of 2000  mg/kg bw and observed every day for 14 days.

Oral LD₅₀Females = higher than 2000  mg/kg bw.

No clinical signs related to the administration of the test item at 2000 mg/kg bw were observed.

The body weight evolution of the animals treated at 2000 mg/kg bw remained normal throughout the study and no treatment-related changes were revealed through macroscopical examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The LD50 of the test substance p-Hydroxybenzoic acid is greater than 2000 mg/kg.
At 5000 mg/kg b.w. mortality occurs (pre-test with one animal)
Therefore p-Hydroxybenzoic acid does not have to be classified in category 4 according to EU-GHS criteria.

Executive summary:

In an acute oral toxicity study, in a first step 1 female Sprague Dawley rat was given a single oral dose of p-hydroxybenzoic acid at a dose of 5000  mg/kg bw. Death was observed within 3 hours after test item administration.

In a second step a group of 6 female Sprague Dawley rats were given a single oral dose of p-hydroxybenzoic acid at a dose of 2000  mg/kg bw and observed every day for 14 days.

Oral LD₅₀Females = higher than 2000  mg/kg bw.

No clinical signs related to the administration of the test item at 2000 mg/kg bw were observed. The body weight evolution of the animals treated at 2000 mg/kg bw remained normal throughout the study and no treatment-related changes were revealed through macroscopical examination of the animals.