Cyclohexanecarboxylic acid, 1-(2-ethylbutyl)-

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 9, 2010 - February 17, 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study has been performed according to OECD and/or EC guidelines and according to GLP principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1-(2-ethylbutyl)cyclohexane-1-carboxylic acid

EC Number:

619-508-4

Cas Number:

381209-09-2

Molecular formula:

C13 H24 O2

IUPAC Name:

1-(2-ethylbutyl)cyclohexane-1-carboxylic acid

Details on test material:

- Name of test material (as cited in study report): CAT-Acid
- Stability under test conditions: stable
- Storage condition of test material: at room temperature in the dark
- Density: 0.98 g/mL
- pH (1% in water, indicative range): 5.4-5.2

Test animals

Species:

rat

Strain:

other: Crl:WI (outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: 174-192 g
- Fasting period before study: overnight prior to dosing
- Housing: group housing of 3 animals per cage in labeled Macrolon cages (MIV type; height 18 cm.)
- Diet (e.g. ad libitum): pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany); animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Water (e.g. ad libitum): tap water (ad libitum)
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.4 – 21.4ºC
- Humidity (%): 43 - 71%
- Air changes (per hr): approximately 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours artificial fluorescent light and 12 hours darkness per day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSE VOLUME APPLIED:
- 2.041 mL/kg (2000 mg/kg)
- 0.306 mL/kg (300 mg/kg)

Doses:

- 2000 mg/kg (1 group)
- 300 mg/kg (2 groups)

No. of animals per sex per dose:

- 3 females for the 2000 mg/kg dose (1 group)
- 6 females for the 300 mg/kg dose (2 groups)

Control animals:

other: not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: twice daily, the time of death was recorded as precisely as possible.
Bodyweights: Days 1 (pre-administration), 8 and 15 and at death (if found dead or sacrificed after Day 1)
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
- Necropsy of survivors performed: yes
- Other examinations performed: no

Statistics:

No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).

Results and discussion

Preliminary study:

Not applicable

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

At 2000 mg/kg, one female was found dead and one female was sacrificed in extremis, both on Day 2. The remaining animal at 2000 mg/kg and all animals treated at 300 mg/kg survived up to the scheduled study duration.

Clinical signs:

other: - At 2000 mg/kg: lethargy, hunched posture, uncoordinated movements, piloerection, salivation, ptosis, hypothermia and/or yellow genital region between Days 1 and 3 (all animals; for one animal, hunched posture was also noted on Days 6 and 7) - At 300 mg/

Gross pathology:

No abnormalities were found.

Any other information on results incl. tables

Dose level	Number of animals and their sex	Date of treatment	Mortality data
2000 mg/kg	3 females	November 9, 2010	2/3
300 mg/kg	3 females	November 11, 2010	0/3
300 mg/kg	3 females	November 12, 2010	0/3

- The LD50 value, based on OECD guideline 423 and LD50 cut-off values, is considered to be 1000 mg/kg (see Annex 2d of OECD 423)

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

An acute oral toxicity study has been conducted according to OECD 423 and GLP in a total of 9 female rats. A group of 3 female rats were treated at a dose level of 2000 mg/kg. At this dose level, one female was found dead and one animal was sacrificed in extremis both on day 2. Therefore, 2 further groups of 3 female rats were dosed at 300 mg/kg. At this dose level, all animals survived up to the scheduled study duration. Clinical signs observed at the 2000 mg/kg dose level were: lethargy, hunched posture, uncoordinated movements, piloerection, salivation, ptosis, hypothermia and/or yellow genital region between Days 1 and 3 (all animals; for one animal, hunched posture was also noted on Days 6 and 7). At the 300 mg/kg dose level, the observed effects of treatment were hunched posture and piloerection between Days 1 and 4 (all animals). Autopsy revealed no abnormalities. Since at the second dose level of 300 mg/kg no mortality was observed, it is concluded that the LD50 is between 300 and 2000 mg/kg. Therefore based on the results of this study the substance needs to be classified as Acute Tox. Cat.4, Harmful if swallowed (H302) in accordance with the CLP Regulation.