dipropyl cyclohexane-1,2-dicarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

23rd July 2015-25th August 2015

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

yes

Remarks:

Please see "principles of method if other than guideline" section for further explanation.

Principles of method if other than guideline:

Due to an oversight the first sighting investigation was performed using water as the vehicle rather than corn oil as indicated by the vehicle trial. The formulation was satisfactory at 30 mg/mL, however, the error was realised at the second sighting investigation as water was unsuitable as vehicle for the higher concentration (200mg/mL) of test substance. As there is generally greater systemic availability of the test substance when formulated in water compared to corn oil, the absence of toxicity following preparation in water was considered to support escalation of the
dose level in corn oil.

Before the start of the main study it was noticed that an incorrect dose volume (20 mL/kg rather than 10 mL/kg) had been used in the sighting investigations resulting in administration of 600 and 4000 mg/kg rather than 300 and 2000 mg/kg. In the absence of toxicity at either level it was still considered appropriate for the main study to be performed at the limit dose of 2000 mg/kg. Typically the animal used for the sighting investigation counts as one of the five main study animals, however, as no animals received 2000 mg/kg during the sighting investigations the
main study was performed with five animals.

The test material container was also flushed with nitrogen after each opening. These deviations were considered to have not affected the integrity or validity of the study.

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2-dipropyl cyclohexane-1,2-dicarboxylate

EC Number:

805-172-8

Cas Number:

65646-25-5

Molecular formula:

C14 H24 O4

IUPAC Name:

1,2-dipropyl cyclohexane-1,2-dicarboxylate

Test material form:

other: Liquid

Details on test material:

- Name of test material (as cited in study report): CHP
- Physical state: Colourless Liquid
- Analytical purity: 98.6%
- Lot/batch No.:ST111209
- Expiration date of the lot/batch:31 December 2016
- Storage condition of test material:Room temperature (ca. 20°C), in the dark, under gaseous nitrogen

Test animals

Species:

rat

Strain:

other: RccHan®:WIST albino rats

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source:Harlan (UK) Ltd
- Age at study initiation:eight to twelve weeks of age
- Weight at study initiation:165 to 184 g
- Housing: Animals were housed inside a barriered rodent facility (Building F21, Room 044/045)
- Diet (e.g. ad libitum):Aspen chew block for environmental enrichment
- Water (e.g. ad libitum):Potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):19 to 23°C
- Humidity (%):40 to 70%
- Air changes (per hr):The animal room was kept at positive pressure with respect to the outside by its own supply of filtered fresh air, which was passed to atmosphere and not re-circulated.
- Photoperiod (hrs dark / hrs light):Artificial lighting was controlled to give a cycle of 12 hours continuous light and 12 hours continuous dark per 24 hours.

IN-LIFE DATES: From: Day 1 To: Day 15

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The vehicle used on the second sighting study and the main study was corn oil.

Doses:

The dose levels for the study were chosen in compliance with the study guidelines. As no previous toxicological information was available the initial dose level was selected as 300 mg/kg, however, due to a calculation error the dose level administered was 600 mg/kg.

Doses in the main study was 4000mg/kg.

No. of animals per sex per dose:

5

Control animals:

no

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

There were no deaths during the sighting or main study.

Clinical signs:

other: Piloerection from approximately 30 minutes after dosing was observed for the sighting investigation rat receiving 4000 mg/kg. This sign was not observed from Day 3 onwards indicating recovery. There were no clinical signs observed for the sighting in

Gross pathology:

No abnormalities were noted in any animal (sighting or main study) at the macroscopic examination at study termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute median lethal oral dose (LD50) to rats of CHP was demonstrated to be greater than 2000 mg/kg body weight.

Executive summary:

The acute median lethal oral dose (LD50) to rats of CHP was demonstrated to be greater than 2000 mg/kg body weight.