2,2,2,4,4,4,4-heptakis[(2-ethylhexanoyl)oxy]cyclodimolybdoxan-2-yl 2-ethylhexanoate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

03 March 2011 to 22 June 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study was conducted in accordance with International Guidelines (OECD 423) and in accordance with OECD Principles of Good Laboratory Practice as incorporated into the United Kingdom (Statutory Instrument for GLP).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

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:

2,2,2,4,4,4,4-heptakis[(2-ethylhexanoyl)oxy]cyclodimolybdoxan-2-yl 2-ethylhexanoate

EC Number:

700-831-5

Molecular formula:

Mo2O2L8 (L = 2-ethylhexanoic acid; C8H16O2) (L' = 2-ethylhexanoic acid; C8H16O2)

IUPAC Name:

2,2,2,4,4,4,4-heptakis[(2-ethylhexanoyl)oxy]cyclodimolybdoxan-2-yl 2-ethylhexanoate

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Nine female (nulliparous and non-pregnant) rats of the Sprague-Dawley Crl:CD(SD) strain were used. The animals were supplied by Charles River, Margate, UK and arrived at Charles River, Edinburgh on 08 March 2011. They were approximately 7-8 weeks old and weighed between approximately 176 and 188 g at despatch.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

300 mg/kg was selected as the starting dose level for administration to Group 1 animals after reviewing the test item documentation. No adverse signs were observed in these animals and, consequently, 2000 mg/kg was selected for administration to Group 2 animals. Adverse signs in these animals were transitory and so a 3rd group of rats was treated at the same dose level to complete the study.

No. of animals per sex per dose:

3 animals per dosing group, three dosing groups in total (see above).

Control animals:

no

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There was one unscheduled death during the observation period. Animal No. 5 swallowed its gavage tube during dosing on Day 1 and was euthanised for humane reasons. The data obtained from this animal were, therefore, incomplete. This did not affect the Study Director’s interpretation of the study findings.
There were no other unscheduled deaths in rats that were treated with HCAT at dose levels of either 300 or 2000 mg/kg.

Clinical signs:

other: No adverse signs of reaction to treatment were recorded in any animal that received HCAT at a dose level of 300 mg/kg. All 5 of the surviving animals that received HCAT at 2000 mg/kg displayed hunched appearance and subdued behaviour. The time of onset wa

Gross pathology:

Macroscopic abnormalities were restricted to the animal that was euthanised on Day 1 after swallowing its gavage tube (Animal No. 5). The tube was found in the animal’s oesophagus and stomach and there were also abnormal contents in the stomach. These contents were described as dark fluid and they are assumed to be test item.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study the median lethal oral dosage (LD50) in Sprague-Dawley rats was considered to be > 2000 mg/kg.

Executive summary:

The objective of this study was to assess the adverse effects which can follow within a short period of time after a single oral administration of HCAT, an organometallic complex, to female rats.

The study design was as follows:

Group Numbers	Animal Numbers	Test Item	Dose Level (mg/kg)	Dose Volume (mL/kg)
1	1 -3	HCAT	300	0.27
2	4 -6	HCAT	2000	1.8
3	7 -9	HCAT	2000	1.8

The following parameters and end points were evaluated in this study: clinical signs, body weights, body weight changes, and gross necropsy findings.

There was one unscheduled death during the observation period. Animal No. 5 swallowed its gavage tube during dosing on Day 1 and was euthanised for humane reasons.

No adverse signs of reaction to treatment were recorded in any animal that received HCAT at a dose level of 300 mg/kg. On the day of dosing all 5 animals treated at 2000 mg/kg displayed hunched appearance and subdued behaviour. In addition, rolling gait and staggering were recorded in 4 of these animals. All signs had resolved by Day 6.

Body weight gain was considered to be acceptable for rats of this age and strain.

There were no necropsy findings in surviving animals. Macroscopic abnormalities were restricted to the animal that was euthanised on Day 1. The gavage tube was found in the animal’s oesophagus and stomach and there were also abnormal contents, presumed to be test item, in the stomach.

Under the conditions of the study the median lethal oral dosage (LD50) in Sprague-Dawley rats was considered to be > 2000 mg/kg.