Phenylsuccinic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2018-05-05 - 2018-06-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

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:

no

Test material

Test material information

Constituent 1

Reference substance name:

Phenylsuccinic acid

EC Number:

211-238-1

EC Name:

Phenylsuccinic acid

Cas Number:

635-51-8

Molecular formula:

C10H10O4

IUPAC Name:

2-phenylbutanedioic acid

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Molecular formula:
C10H10O4
Molecular Mass:
194.18
Characteristics (Physical Appearance):
White Crystalline powder
CAS No.:
[635-51-8]
Batch Number:
123
Purity:
100%

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Source:
INTOX PVT. LTD.
Age at start of treatment:
8 to 9 weeks
Weight range at start of the treatment (Day -1):
148 g to 171 g
Route of administration and justification of its choice:
Oral, through gavage. The oral route is an accidental route of exposure in humans.
No. of dose groups:
Four: Steps-1 and 2: 300 mg/kg ; Steps-3 and 4 : 2000 mg/kg body weight
No. of animals per dose group:
Three
Veterinary examination:
Prior to assignment to the study, the animals were subjected to a veterinary examination to ensure that the selected rats were in a good state of health.
Environmental conditions:
The experimental animal room was supplied with fresh and filtered air, with 10 to 15 air changes per hour. The room was air conditioned with temperature between 19 to 25 °C, relative humidity 30 to 70% and illumination cycle was set to 12 hours light and 12 hours dark.
Accommodation:
Animals were housed in room number AR-05, in the experimental animal facility of INTOX PVT. LTD., maintained under appropriate barriers.
Animals were housed in sterilised solid bottom polypropylene cages [size: 42 cm (L) x 29 cm (W) x 19 cm (H)] with stainless steel grill tops, facilities for food and water bottle, and with bedding of clean and sterilised paddy husk. Cages were suspended on movable stainless steel racks.
Animals were group housed, with three animals of same dose group being housed in one cage.
Diet:
'Altromin' brand pelleted rat feed manufactured by M/s Altromin Spezialfutter GmbH & Co. KG, Germany, and supplied by ATNT Laboratories, Mumbai was provided ad libitum.
Certificates of nutrient analysis for each batch of diet used have been retained in the facility records. The diet has been tested and certified to be free from undesired levels of contaminants.
Water:
Potable water passed through 'Aquaguard' water filter was provided ad libitum in sterilized bottles with stainless steel sipper tubes.
The drinking water has been tested and certified for potability and the water source has been verified to be free from undesired levels of contaminants.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.2% Tween 80

Details on oral exposure:

The test item was administered by oral gavage to each rat as a single dose using a suitably graduated syringe and a stainless steel intubation needle (16G). The dose administered to individual rat was adjusted according to its body weight that was recorded just before dosing to give a constant dosage volume of 10 ml/kg body weight.

Doses:

No. of dose groups:
Four: Steps-1 and 2: 300 mg/kg ; Steps-3 and 4 : 2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

The toxicity of the test item was assessed by stepwise treatment of animals. Three female rats were used per step. Absence or presence of compound-related mortality of the animals dosed at one step determined the next step, i.e. either no further testing is needed or dosing of three additional animals with the same dose or dosing of three additional animals at the next higher / lower dose level.
Following their treatment, the rats were observed for incidence of mortality and signs of toxicity for 14 days.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

none

Clinical signs:

other: none

Gross pathology:

no effects

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item, 2-Phenylsuccinic Acid, is classified in GHS Category 5 or unclassified for the obligatory labelling requirement for oral toxicity, the corresponding LD50 cut-off value being 5000 mg/kg body weight.

Executive summary:

Acute oral toxicity study of 2-Phenylsuccinic Acid in Wistar rats was performed as per Organization for Economic Co-operation and Development (OECD) Guidelines for Testing of Chemicals, Section 4, No. 423 - Acute Oral Toxicity - Acute Toxic Class Method, adopted by the council on 17 December, 2001. The method uses pre-defined doses and the results allow a substance to be ranked and classified according to the Globally Harmonised System (GHS) for classification of chemicals which cause acute toxicity.

In this study, single oral administration of 2-Phenylsuccinic Acid was made to groups of three female Wistar rats in step-wise manner to assess its acute toxicity.

The test item was formulated in analytical grade water with 0.2% Tween 80 to obtain concentrations of 30 mg/ml and 200 mg/ml.

Following the starting dose of 300 mg/kg body weight, which was also repeated in the step 2 of the study, 2-Phenylsuccinic Acid did not cause death of any of the treated female rats and did not induce any abnormal clinical signs. Body weights of treated rats were not adversely affected during the observation period. No gross pathological alterations were encountered in any of the female rats when sacrificed at termination of the study.

Following step 3, at the dose of 2000 mg/kg body weight, which was also repeated in step 4 of the test, 2-Phenylsuccinic Acid did not cause death of any of the treated rats and did not induce any any abnormal clinical signs. Body weights of treated rats were not adversely affected during the observation period. No gross pathological alterations were encountered in any of the female rats when sacrificed at termination of the study.

Based on these results, and according to the criteria for classification (described under section 3.5 of this report) viz. Globally Harmonised System (GHS) for classification of chemicals which cause acute toxicity, Seventh Revised Edition (ST/SG/AC.10/30/Rev.7); United Nations, New York and Geneva, 2017; eISBN 978-92-1-060457-4, United Nations, 2017 and the EC Requirements for Classification and Labelling of Dangerous Substances (Commission Directive 2001/59/EC of 6th August 2001 adapting to technical progress for the 28th time Council Directive 67/548/EEC on the approximation of the laws, regulations and administrative provisions relating to the Classification, Packaging and Labelling of Dangerous Substances. Official Journal of the European Communities OJL 225 pp. 1-333), the test item, 2-Phenylsuccinic Acid, is classified in GHS Category 5 or unclassified for the obligatory labelling requirement for oral toxicity, the corresponding LD50 cut-off value being 5000 mg/kg body weight.