(-)-trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

other: extracted from ECHA database

Title:

Unnamed

Year:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(-)-trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

EC Number:

406-030-4

EC Name:

(-)-trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

Cas Number:

105812-81-5

Molecular formula:

C13H18FNO

IUPAC Name:

(-)-trans-4-(4'-fluorophenyl)-3-hydroxymethyl-N-methylpiperidine

Test animals

Species:

rat

Strain:

Sprague-Dawley

Administration / exposure

Route of administration:

oral: unspecified

Vehicle:

other: 1% (w/v) aqueous methyl cellulose

Doses:

200, 431, 928, 2000 mg/kg

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

929 mg/kg bw

95% CL:

719 - 1 199

Mortality:

0/5 Male/female deaths at 200 mg/kg bw
0/5 Male/female deaths at 431 mg/kg bw
2/5 male and 3/5 female deaths at 928 mg/kg bw
5/5 Male/female deaths at 2000 mg/kg bw

Clinical signs:

Clinical signs were seen in all dose groups within 1 hr of dosing and consisted of hunched posture, pilo-erection, body tremors, excessive salivation, decreased reapiration and (at 431 mg/kg and above) lethargy. Animals receiving 200 mg/kg had recovered by 4 hr after dosing, as had females receiving 431 mg/kg. Males receiving 431 mg/kg and all surviving animals receiving 928 mg/kg continued to show hunched posture and pilo-erection on day 1 (24-48 hr) after dosing but were normal bu day 2.
Isolated animals receiving 2000 mg/kg showed clonic and tonic convultions in addition to the clinical symptoms described above and all animals had died by day 2. All surviving animals showed normal bodyweight gain throughout the study period.

Gross pathology:

Surviving animals showed no abnormality at necropsy with the exception of haemorrhage of the glandular stomach in 1 female receiving 200 mg/kg and the finding of serveral white raised areas in the glandular stomach of one male receiving 431 mg/kg. Decedents showed dark or dark red lungs and livers, pallor of the spleen and haemorrhaging or congestion of the small intestine was also noted. One male and one female receiving 928 mg/kg were not necropsied due to cannibalism.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Although there was a slight difference in the LD50 for females (860 mg/kg) and male (between 928 and 2000 mg/kg estimated), this is of little toxicological significance, and doed not affect the classification of the substance, which on the results of this study must be classified as harmful .