4-(octadecylamino)-4-oxoisocrotonic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 - 30 Aug 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Slovak National Accreditation Service, Karloveska 63, 840 00 Bratislava 4, Slovak Republic

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-(octadecylamino)-4-oxoisocrotonic acid

EC Number:

221-361-2

EC Name:

4-(octadecylamino)-4-oxoisocrotonic acid

Cas Number:

3077-27-8

Molecular formula:

C22H41NO3

IUPAC Name:

4-(octadecylamino)-4-oxoisocrotonic acid

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 180 - 205 g
- Fasting period before study: over night and 3 - 4 h post-administration
- Housing: 3 animals per cage
- Bedding: Lignocel S3/4, Lufa - ITL GmbH, Germany
- Diet: ssniff (Spezialdiäten GmbH, Germany), provided at recommended doses each day approximately at the same time
- Water: tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23.18 ± 0.45
- Humidity (%): 55.40 ± 3
- Air changes (per hr): not specified
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To: 15 - 30 August 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Olive oil is a standard vehicle according to OECD 423
- Lot/batch no.: L63417
- Expiry date: 06/2018
- Manufacturer: Oleificio Luca, Italy
- Storage temperature (°C): 20 ± 5

CLASS METHOD (if applicable):
- Rationale for the selection of the starting dose: Available information indicated that the test item is likely to be non-toxic with regard to acute toxicity. Hence, the limit dose of 2000 mg/kg body weight was used as a starting dose.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: immediately after dosing, 0.5, 1, 2 and 4 h after administration
- Frequency of weighing: immediately prior to dosing and weekly thereafter
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 is cut-off according to OECD 423

Mortality:

All (6/6 females) animals survived the limit dose of 2000 mg/kg body weight.

Clinical signs:

During the observation period, no animals displayed signs of intoxication, change of health, or any other adverse reaction.

Body weight:

The body weight of all animals increased during the study. No body weight losses were observed between the first and second week after administration.

Gross pathology:

During necropsy, no macroscopic findings were observed.

Any other information on results incl. tables

Table 1: Body Weights and Body Weight Differences

 

Sex	Dose	ID	Body Weight (g)			Body Weight Difference (g)
			Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 - Week 1
♀	2000 mg/kg	1	205	210	215	5	10	5
		2	185	190	200	5	15	10
		3	190	190	200	0	10	10
		4	190	200	205	10	15	5
		5	190	200	210	10	20	10
		6	180	210	220	30	40	10

Applicant's summary and conclusion

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No. 1272/2008.

Conclusions:

The LD50 of the test item has been determined to be greater than 2000 mg/kg body weight after single oral administration to female Wistar rats.

Based on 'Annex 2d Test Procedure with a Starting Dose of 2000 mg/kg body weight' of OECD 423 it can also be concluded that the LD50 cut-off value is equal to or greater than 5000 mg/kg body weight after single oral administration to Wistar rats.