Registration Dossier

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:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
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 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 levelsopen allclose all
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
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:
no clinical signs at 2000 mg/kg b.w.
Body weight:
no abnormal changes or reductions in body weight 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.