(1R,2S,5R)-2-isopropyl-N-(4-methoxyphenyl)-5-methylcyclohexanecarboxamide

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw (OECD 420; GLP; female rats)

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:

2008-06-10 to 2008-07-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

, adopted 2001-12-17

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

, 2004

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

signed 2007-10-15

Test type:

fixed dose procedure

Limit test:

no

Species:

rat

Strain:

other: Sprague-Dawley CD

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan UK Limited, Bicester, Oxon, UK
- Age at study initiation: eight to twelve weeks of age
- Weight at study initiation: 151 g - 190 g
- Fasting period before study: overnight fast immediately before dosing and for approximately three to four hours after dosing
- Housing: housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet (ad libitum; exception: see "Fasting period before study" above): Certified Rat and Mouse Diet
- Water (ad libitum): mains drinking water
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature : 19 to 25 °C
- Relative humidity: 30 to 70 %
- Air changes: at least fifteen changes per hour
- 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: arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg; the volume administered to each animal was calculated according the the fasted bodyweight at the time of dosing.

Doses:

300 mg/kg (sighting study)
2000 mg/kg (sighting study / main study)

No. of animals per sex per dose:

300 mg/kg: one female (sighting study)
2000 mg/kg: five females (sighting study/main study)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing:
clinical observations: 0.5, 1, 2 and 4 hours after dosing and then daily for fourteen days.
morbidity and mortality checks: twice daily
individual bodyweights: Day 0 (the day of dosing) and on Days 7 and 14.

- Necropsy of survivors performed: yes, at the end of the observation period the animals were killed and all animals were subjected to gross necropsy consisting of external examination and opening of the abdominal and thoracic cavities.

Statistics:

Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) was made.

Preliminary study:

First, a single animal was treated with 300 mg/kg. There was no mortality. No signs of systemic toxicity were noted and the animal showed expected gains in body weight during the observation period. No abnormalities were noted at necropsy.
In the absence of toxicity, an additional animal was treated with 2000 mg/kg. In the absence of toxicity, an additional group of four animals was treated with 2000 mg/kg.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

2000 mg/kg: 100 % survival.

Clinical signs:

other: 2000 mg/kg: no signs of systemic toxicity during observation period.

Gross pathology:

2000 mg/kg: no abnormalities were observed at the necropsy

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

LD50 (female rats) > 2000 mg/kg bw
According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not acutely toxic via the oral route.

Executive summary:

The acute oral toxicity of the test substance was investigated according to the OECD guideline 420 (2001). Four female Sprague-Dawley CD rats received a single dose of 2000 mg/kg bw in peanut oil by gavage. All animals were subjected to gross necropsy. Mortality, clinical signs or abnormalities at necropsy were not observed during the study. Furthermore, all animals gained the expected weight during the observation period. Thus, the LD50 is estimated with > 2000 mg/kg bw for female rats. According to the Regulation (EC) No 1272/2008 and subsequent adaptations, the test item is not acutely toxic via the oral route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

The substance was not observed to be acutely toxic orally to female rats in a reliable study according to OECD 420. The LD50 was determined to be greater than 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
GLP guideline study conducted with the test item

Justification for classification or non-classification

Acute oral toxicity

The substance is not acutely toxic via the oral route based on an acute oral toxicity test (OECD 420) and does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.

Specific target organ toxicant (STOT) - single exposure: oral

Reversible or irreversible adverse health effects were not observed immediately or after exposure in an acute oral toxicity test (OECD 420). Thus, the classification criteria as specific target organ toxicant (STOT) – single exposure, oral are not met and the substance does not require classification according to Regulation (EC) No 1272/2008 and subsequent adaptations.