4-nitrophenyl acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Acetic acid, 4-nitrophenyl ester

IUPAC Name:

Acetic acid, 4-nitrophenyl ester

Constituent 2

Reference substance name:

4-nitrophenyl acetate

EC Number:

212-593-5

EC Name:

4-nitrophenyl acetate

Cas Number:

830-03-5

Molecular formula:

C8H7NO4

IUPAC Name:

4-nitrophenyl acetate

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): 4-Nitrophenyl Acetate

- Physical state: solid
- Analytical purity: 95 % w/w
- Impurities (identity and concentrations):
Phenol <5.0 % (w/w)
4-nitrophenol <5.0 % (w/w)
Acetic acid <1.0 % (w/w)
Water <5.0 % (w/w)

- Lot/batch No.: 201409
- Expiration date of the lot/batch: unlisted

- Storage condition of test material: During the study the test substance was stored in closed
container in the dark at laboratory temperature.
-pH approx. 7, by contact of application form with universal indicator pH strip moistened with water

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeding farm VELAZ s.r.o., Únětice, Czech Republic,
RČH CZ 21760152
- Age at study initiation: 6-7 weeks at the time application
- Weight at study initiation: no data
- Fasting period before study: yes
- Housing: animal room with monitored conditions – 3 animals of one sex in one plastic breeding cage Velaz T4
- Diet (e.g. ad libitum): complete pelleted standard diet for experimental animals ad Libitum (VELAS, a.s., Hrabanov 535, 289 22 Lysá n/L, Czech Republic, CZ 801080-01)
- Water (e.g. ad libitum): drinking tap water ad libitum (quality corresponding to Regulation No. 252/2004 Czech Coll. of Law)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): room temperature 22 + 3°C, permanently monitored
- Humidity (%): relative humidity 30 – 70 %, permanently monitored
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): light period 12-hour light/12 hour dark

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
Aqua pro injectione
Batch No.: 1501210041
Expiration: 01/2017
Manufacturer: ARDEAPHARMA a.s. Ševětín, Czech Republic

Doses:

300 - 2000 -2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observation: day 1: 30 minutes and 3 hours after application., day 2: twice, than daily for 14 days; weighing: day 8 and day 15
- Necropsy of survivors performed: yes
- Other examinations performed: Observations included changes in skin and fur, eyes, visible mucous membranes, behaviour of animals, somatomotor activity, reactions to stimuli, and presence of lacrimation, salivation and discharge from nostrils, function of respiratory, digestive and urogenital system.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD0

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed.

Clinical signs:

other: No clinical signs of intoxication were observed after dosing 300 and 2000 mg/kg/body weight

Gross pathology:

No pathologic macroscopic changes were diagnosed during pathological examination

Any other information on results incl. tables

Table No. 1: Individual body weight (g) – 300 mg/kg (Steps No. 1)

Dose (mg/kg) (Step No.)	Animal No.	Body weight (g)	Body weight gain (g)
Before application	8 days p.a.	15 days p.a.	1-8 days p.a.	8-15 daysp.a.
300(1)	1	138.31	176.06	199.74	34.75	23.68
2	125.59	160.58	179.13	34.99	18.55
3	124.66	159.29	176.62	34.63	17.33
mean	129.52	165.31	185.16	35.79	19.85
SD	7.63	9.33	12.69	1.71	3.37

Table No. 2: Individual body weight (g) – 2000 mg/kg (Steps No. 2 and No. 3)

Dose (mg/kg) (Step No.)	Animal No.	Body weight (g)	Body weight gain (g)
Before application	8 days p.a.	15 days p.a.	1-8 days p.a.	8-15 daysp.a.
2000(2)	4	129.79	164.32	186.14	34.53	21.82
5	139.43	168.18	199.22	28.75	31.04
6	131.58	163.25	184.29	31.67	21.04
mean	133.60	165.25	189.88	31.65	24.63
SD	5.13	2.59	8.14	2.89	5.56
2000(3)	7	138.39	172.96	194.77	34.57	21.81
8	145.56	178.59	199.00	33.03	20.41
9	153.90	186.42	202.60	32.52	16.18
mean	145.95	179.32	198.79	33.37	19.47
SD	7.76	6.76	3.92	1.07	2.93

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

According to the study results the value of LD50 of the test substance, 4-Nitrophenyl Acetate, for female rats is higher than 2000 mg/kg of body weight.

Executive summary:

The test substance toxicity was evaluated on the basis of mortality, clinical signs of intoxication, body weight increments during the observation period and necropsy findings at the end of study.

The test substance administered at the dose of 300 and 2000 mg/kg caused no death of animals.

No clinical signs of intoxication were detected during the whole study in all nine animals.

No pathologic macroscopic changes were diagnosed during pathological examination.