3-Methyl-cyclohexanecarboxylic acid methyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 April - 29 July 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Study in accordance with recognised test method

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF, 12 Nohsan No. 8147

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Reference

Name:

Unnamed

Type:

Constituent

Test animals

Species:

rat

Strain:

other: CD (Crl:CD ‘SD’)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 196-268 g
- Fasting period before study: overnight
- Housing: solid bottomed polycarbonate cages with a stainless steel mesh lid
- Diet (e.g. ad libitum): standard rodent diet (Rat and Mouse No. 1 Maintenance Diet)
- Water (e.g. ad libitum): potable water taken from the public supply was freely available via polycarbonate bottles fitted with sipper tubes
- Acclimation period:at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40 to 70%
- Air changes (per hr): not specified
- 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: 4 April 2008 To: 13 May 2008

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30mg/l and 200 mg/l
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: not specified

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 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 300 mg/kg.

Doses:

300 mg/kg or 2000 mg/kg

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?) 14 days

- Frequency of observations and weighing: Animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, surviving animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation.The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15 or at death. Individual weekly bodyweight changes and group mean bodyweights were calculated.

- Necropsy of survivors performed: All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: mortality, clinical observations, bodyweight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 300 - <= 2 000 mg/kg bw

Mortality:

One female dosed at 2000 mg/kg bodyweight was found dead at the first observation period on Day 2 and another female dosed at this level was found dead at the second observation period on Day 2.

Clinical signs:

Clinical signs prior to death in both animals comprised hunched posture, unsteady gait, piloerection, increased breathing, irregular breathing, reduced body tone, underactivity, flat posture, prostrate posture, lachrymation, reduced body temperature, shallow breathing, red staining in urine (one animal only) and partially closed eyelids. In addition, one female also showed yellow/brown staining in the perigenital area, along with uncoordinated gait.

Body weight:

A loss in bodyweight was recorded for both decedents.

Gross pathology:

Macroscopic examination revealed in both animals congestion (darkened tissues/organ) of the subcutaneous tissue, heart, lungs, liver (one animal only), spleen, kidneys and duodenum, enlarged stomach and urinary bladder (one animal only) atrophy of the caecum, yellow fluid contents in the stomach and small intestines and red fluid contents in the large intestines

Other findings:

Clinical signs of reaction to treatment in the surviving female treated at 2000 mg/kg bodyweight comprised hunched posture, unsteady gait, piloerection, increased breathing, underactivity, flat posture, muscle tremors, reduced body temperature, yellow/brown staining in the perigenital area, prominent eyes and thin build. All of these signs had resolved as judged by external appearance, by Day 10.

Clinical signs seen in females dosed at 300 mg/kg bodyweight comprised unsteady gait seen in five animals and loose faeces were noted in two animals. These signs had all resolved as judged by external appearance, by Day 2.

Low bodyweight gains were noted for three surviving animals dosed at 2000 mg/kg bodyweight and one animal dosed at 300 mg/kg bodyweight, all on Day 15. All other surviving animals were considered to have achieved satisfactory bodyweight gains throughout the study.

The macroscopic examination of surviving animals terminated on Day 15 revealed atrophy of the stomach in one female dosed at 2000 mg/kg bodyweight. No abnormalities were noted in the other surviving animals at the macroscopic examination at this time.

Applicant's summary and conclusion

Conclusions:

The acute median lethal oral dose (LD50) to rats of M3MC-Carboxylate was demonstrated to be between 300 and 2000 mg/kg bodyweight.

M3MC-Carboxylate is included in Category 4, according to the Globally Harmonised System (GHS), (UNITED NATIONS, 2005).

Executive summary:

The acute median lethal oral dose (LD50) to rats of M3MC-Carboxylate was demonstrated to be between 300 and 2000 mg/kg bodyweight. M3MC-Carboxylate is included in Category 4, according to the Globally Harmonised System (GHS), (UNITED NATIONS, 2005).