Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well documented study according to international accepted guidelines and GLP compliant.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

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:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Test item 4-nitrophenyl-acetic acid
Batch No. 0046D93
Physical state solid, crystalline powder
Colour yellowish to yellow-brownish
Storage cool, dry place, protected from light

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
Species and strain: Crl:(WI)Br rats
Source: TOXI COOP ZRT.
Hygienic level at arrival: SPF
Hygienic level during the study: good conventional
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 11 weeks old in first and second step
Body weight range at starting (first step): 198 - 200 g
Body weight range at starting (second step): 193 - 202 g
Acclimatization time: 28 days in first step and 29 days in second step
Animal health: Only healthy animals were used for the study. Health status was certified by the study director.

Housing: Group caging (3 animals/cage)
Light: Artificial light, from 6 a.m. to 6 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 10-15 air exchanges/hour by central air-condition system.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: methyl cellulose (0.5 %) aq. solution
Details on oral exposure:
A single oral administration - followed by a fourteen-day observation period - was performed by gavage.
An acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level, therefore treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished.

The dose used was formulated in the vehicle. Concentration of formulation was adjusted to maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration of 200 mg/mL. Formulation were prepared just before the administration and stirred continuously during the treatment.

The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 female/dose
Control animals:
no
Details on study design:
The obresvation period was 14 days. Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, 5 h and 6 h after the treatment and twice each day for 14 days thereafter.
The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.
At the end of the observation period rats were sacrificed and necropsy were performed.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No death occurred at 2000 mg/kg bw single oral dose of 4-nitrophenyl-acetic acid. All female rats in step 1 and step 2 survived until the end of the 14-day observation period.
Clinical signs:
No treatment related symptoms were observed throughout the 14-day post-treatment period at any groups of the female animals.
Body weight:
The mean body weight of animals corresponded to their species and age throughout the study.
Gross pathology:
All animals survived until the scheduled necropsy on Day 15.
No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Any other information on results incl. tables

Groups

Treatment

Lethality

Testitem

Dose (mg/kgbw)

Females

1

“4-nitrophenyl-acetic acid
Step1

2000

0/3

2

“4-nitrophenyl-acetic acid
Step 2

2000

0/3

 

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The method used, was not intended for the precise calculation of a precise LD50 value.
The result of the test was not conclusive to confirm GHS Category V, because there wasn't any mortality observed at 2000 mg/kg bw.
The test item can not be classified.