Barium(2+) 12-hydroxyoctadecanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 2017-10-24 to 2017-11-22

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

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

17 December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

440/2008/EC, 31 May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

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:

Barium(2+) 12-hydroxyoctadecanoate

EC Number:

244-469-1

EC Name:

Barium(2+) 12-hydroxyoctadecanoate

Cas Number:

21598-22-1

Molecular formula:

C18H36O3.1/2Ba

IUPAC Name:

barium bis(12-hydroxyoctadecanoate)

Test material form:

solid

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: Lab NP_20171034-003
- Expiration date of the lot/batch: 2022-08-18

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: closed vessel at room temperature (20±5°C).

OTHER SPECIFICS:
white solid

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90., Hungary
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 11 weeks old
- Weight at study initiation:
Body weight range at starting (first step): 218-224 g
Body weight range at starting (second step): 231-237 g
- Fasting period before study: The day before treatment the animals were fasted. The food but not water was withheld overnight
- Housing: 3 animals/sex/cage in Type III polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.
- Diet: ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum.
- Water: tap water from watering bottles ad libitum.
- Acclimation period: 26 days in first step and 27 days in second step

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30 - 70
- Air changes (per hr): above 10
- Photoperiod (hrs dark / hrs light): 12/12 from 6 am. to 6 pm.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui oleum raffinatum

Remarks:

Manufactured: Parma Produkt Kft.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle: 10 mL/kg bw

- Batch no.: 1703-4281

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw


CLASS METHOD
- Rationale for the selection of the starting dose: Starting dose was selected on the basis of the available information about the test item.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

three female rats/step

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Inspection for signs of morbidity and mortality were made twice daily at the beginning and end of the working day. Animals were observed individually after dosing once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, after the treatment and once per day for 14 days thereafter. Individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. The body weight were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 on all animals with a precision of 1 g, respectively.
- Necropsy of survivors performed: yes, All animals were subjected to gross pathology. All animals were exsanguinated under isoflurane anaesthesia. After examination of the external appearance the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs were observed. All gross pathological changes were recorded for each animal on the post mortem record sheets.
- Other examinations performed: gross pathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. All female rats survived the performed treatment until the end of the 14-day observation period.

Clinical signs:

other: No treatment related symptoms were observed throughout the treatment day and 14-day post-treatment period at any groups of the female animals.

Gross pathology:

All animals treated with 2000 mg/kg bw dose of test item survived until the scheduled necropsy on Day 15. Slight hydrometra was detected in one animal of group 1. Hydrometra is a physiological finding and connected to the oestrus cycle of the animal. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity assay according to OECD guideline 423 (acute toxic class method, ATC), an LD50 of above 2000 mg/kg bw was determined.

Executive summary:

An acute oral toxicity study was carried out using the class method according to OECD guideline 423. The starting dose was selected on the basis of the available information about the test item. The 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 young adult (11 weeks old) female Wistar rats followed by a 14 days observation period. 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. Again, no animal died in the second step, thus, no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix 7) were met.

Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on 15th day after the treatment.

In first and second step, no clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal. The body weight development was normal in all animals.

Altogether 6 animals were subjected to scheduled sacrifice during the study. All organs of the animals treated with 2000 mg/kg bw dose proved to be free of treatment related gross pathological changes.

The method used is not intended to allow for the calculation of a precise LD50 value. However for this acute oral toxicity study with the test item in rats the determined LD50 is greater than 2000 mg/kg bw.