Benzoic acid, 4-[2-[2-oxo-1-[(phenylamino)carbonyl]propyl]diazenyl]-

Acute Toxicity: oral

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: GLP- and Guideline Study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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-[(1E)-2-[2-oxo-1-(phenylcarbamoyl)propyl]diazen-1-yl]benzoic acid

EC Number:

603-014-0

Cas Number:

124772-04-9

Molecular formula:

C17 H15 N3 O4

IUPAC Name:

4-[(1E)-2-[2-oxo-1-(phenylcarbamoyl)propyl]diazen-1-yl]benzoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS

- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy.
- Age at study initiation: 6 to 8 weeks (nulliparous and non-pregnant)
- Weight at study initiation: 176 to 200 grams
- Fasting period before study: no data
- Housing: Polycarbonate cages measuring 42.5x26.6x18.0 cm with a stainless steel mesh lid and floor. Cages were suspended over trays holding an absorbent material which was inspected daily and changed as necessary. Throughout the study each cage was identified by a colour coded label recording the study number, animal numbers and the details of treatment.
- Diet (e.g. ad libitum): Commercially available laboratory rodent diet (4RF1S, Mucedola S.r.l, Via G. Galilei, 4, 20019 Settimo Milanese (MI), Italy) ad libitum throughout the study except for an overnight fast prior to dosing and a period of approximately 4 hours after dosing.
- Water (e.g. ad libitum): drinking water supplied to each cage via a water bottle
- Acclimation period: 5 d

ENVIRONMENTAL CONDITIONS

- Temperature (°C): 22°C ± 2°C .
- Humidity (%): 55% ± 15%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

On the day of dosing, the amount of the formulated test item to be administered was
calculated for each fasted animal according to body weight. This was administered, by
gavage at a dose volume of 10 ml/kg, using a rubber catheter attached to a syringe of suitable
capacity.
Animals were dosed once only.
Food was made available approximately 4 hours after dosing.

Doses:

2000 mg/kg, 300 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

Experimental design
A single group of 3 females was dosed at a level of 2000 mg/kg (step 1). Mortality occurred and a group of 3 females was subsequently dosed at 300 mg/kg (step 2). Since no mortality occurred a third group of 3 females was dosed at the same dose level (step 3).

Selection and allocation
The required number of animals for the study was allocated to treatment groups. Individuals were permanently identified following arrival by a combination of ear notch (units) and tattoo on the feet. Animals were identified by odd numbers. The body weight of each individual was within 20% of the mean.

Single groups of 3 female animals were allocated to the study as follows:

Dose level Step Animal number
(mg/kg) Females
2000 1 147,149,151
300 2 7,9,11
300 3 13, 15,17

Food was removed from cages overnight prior to dosing.

Dosing
On the day of dosing, the amount of the formulated test item to be administered was calculated for each fasted animal according to body weight. This was administered, by gavage at a dose volume of 10 ml/kg, using a rubber catheter attached to a syringe of suitable
capacity. Animals were dosed once only. Food was made available approximately 4 hours after dosing.

Mortality and morbidity
Throughout the study all animals were checked twice daily.

Clinical signs
Animals were observed for clinical signs immediately upon dosing, approximately 30 minutes, 2 and 4 hours after dosing and daily thereafter for a total of 14 days, where appropriate.

Body weight
All animals were weighed at allocation to the study (Day -1), immediately prior to dosing (Day 1) and on Days 2, 8 and 15, where appropriate. Early decedent animals were weighed when found dead.

Termination
Surviving animals were killed on Day 15 by carbon dioxide narcosis. All animals, including those found dead, were subjected to a gross necropsy examination for both external and internal abnormalities. The cranial, thoracic and abdominal cavities were opened to allow examination of their contents. Larger organs were sectioned. Both the stomach and representative sections of the gastro-intestinal tract were opened for examination of the mucosal surfaces.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Following dosing a single group of 3 female animals at 2000 mg/kg (step 1), two animals died on Day 2.
No mortality occurred following dosing the first 3 female animals at 300 mg/kg (step 2).
No mortality occurred in the second 3 females dosed at 300 mg/kg (step 3).

Clinical signs:

other: 2000 mg/kg: Clinical signs observed in all animals on the day of dosing were piloerection, Recovery occurred in the surviving animal from Day 2. 300 mg/kg (both groups): The observed clinical signs were piloerection, hunched posture and reduced activity

Gross pathology:

Necropsy examination of the early decedent animals (dosed at 2000 mg/kg) revealed the presence of abnormal contents (yellow,
fluid/mucoid material) in the stomach, duodenum and jejunum. No abnormalities were observed in the surviving animal at the end
of the study. No abnormalities were observed in any animals (dosed at 300 mg/kg) killed on termination of the study.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute toxicity of POLYALKYLENE YELLOW MONOAZO was investigated following administration of a single oral dose to the rat.
Two animals died following dosing at 2000 mg/kg. No mortality or other severe signs of toxicity were observed in animals dosed at 300 mg/kg.
These results indicate that the test item, POLYALKYLENE YELLOW MONOAZO, has a toxic effect in the rat following single oral administration at a dose level of 2000 mg/kg, while a dose level of 300 mg/kg is tolerated. The mortality pattern demonstrates the acute oral LD50 to be less than 2000 mg/kg, but greater than 300 mg/kg body weight.

European Directives concerning the classification, packaging and labelling of dangerous substances (67/548/EEC and subsequent revisions) would suggest the following:

Classification : Required Symbol : Xn R phrase : R22 - Harmful if swallowed

The corresponding classification according to EU Directive 1272/2008 is: Acut Tox 4 (oral), H 302