Reaction mass of bis(2-methylpropyl) (1R,2R,3R,6S)-3,6-dimethylcyclohexane-1,2-dicarboxylate and bis(2-methylpropyl) (1S,2S,3R,6S)-3,6-dimethylcyclohexane-1,2-dicarboxylate

Endpoint summary

Description of key information

LD50 (Oral), Rats >2000 mg/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

09 Aug - 18 Sep, 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Testing Guidelines for Toxicology Studies, No. 2-1-1 “Acute oral toxicity studies”, 12 Nousan No. 8147

Version / remarks:

24 November 2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: H1L002
- Expiration date of the lot/batch: 31 Dec 2017
- Purity test date: 99.0%
- Physical state/Appearance: Colourless to yellow liquid
- Storage Conditions: Room temperature in the dark

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 163 - 180 g
- Fasting period before study: Overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing
- Housing: Suspended solid-floor polypropylene cages furnished with woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25
- Humidity (%): 30 to 70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

BP

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: test item did not dissolve/suspend in distilled water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Note that the above vehicle and dose volume refer to the 300 mg/kg dose level only; the 2000 mg/kg level received test material as supplied (no vehicle used)

Doses:

300 and 2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days.
- Frequency of observations and weighing: Day 0 (the day of dosing) and on Days 7 and 14
- Necropsy of survivors performed: yes

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period

Gross pathology:

No abnormalities were noted at necropsy

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

Database considered reliable as a Guideline (EC and OECD) study conducted according to GHS is available

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

An acute oral toxicity study in rats (Envigo, 2017) recorded no deaths and no indication of sub-lethal toxicity (judges on the basis of an absence of clinical observations or abnormalities seen at necropsy of surviving animals) at dose levels up to 2000 mg/kg. As the LD₅₀ is therefore greater than 2000 mg/kg it may be concluded that SIBE138 should not be classified for acute toxicity by the oral route in accordance with the CLP Regulation (Regulation (EC) 1272/2008 including ATPs up to January 2018). Furthermore it is concluded that there are no indications of Specific Target Organ Toxicity following a single exposure (STOT-SE).

It is noted that there are no available acute toxicity data available by the dermal or inhaled routes.