4'-benzyloxy-2-bromopropiophenone

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

2011

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2011

Report date:

2011

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The test item was administered by gavage to three groups, each of three male and three female Sprague-Dawley Crl:CD® (SD) IGS BR strain rats, for seven consecutive days, at dose levels of 150, 300 and 1000 mg/kg bw/day. A control group of three males and three females was dosed with vehicle alone (Polyethylene glycol 400).
Clinical signs, body weight change, dietary intake and water consumption were monitored during the study. Haematology, blood chemistry and organ weight data were evaluated at the end of the study and all animals were subjected to a gross necropsy examination. Histopathological examination of selected tissues was also performed.

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

4'-benzyloxy-2-bromopropiophenone

EC Number:

252-351-6

EC Name:

4'-benzyloxy-2-bromopropiophenone

Cas Number:

35081-45-9

Molecular formula:

C16H15BrO2

IUPAC Name:

1-[4-(benzyloxy)phenyl]-2-bromopropan-1-one

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Duration of treatment / exposure:

Period of seven consecutive days.

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

150 mg/kg bw/day (nominal)

Doses / concentrations 2

Dose / conc.:

300 mg/kg bw/day (nominal)

Doses / concentrations 3

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

1 Group:3 Female rats/ 3 Male rats - 150 mg/kg bw/day
2 Group:3 Female rats/ 3 Male rats - 300 mg/kg bw/day
3 Group:3 Female rats/ 3 Male rats - 1000 mg/kg bw/day
Control Group:3 Female rats/ 3 Male rats - Vehicle

Control animals:

yes, concurrent vehicle

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Clinical signs were mainly confined to the presence of post-dose increased salivation at all dose levels. One male treated at 1000 mg/kg bw/day showed clinical signs of ptosis, lethargy, hunched posture and respiratory pattern changes.

Mortality:

no mortality observed

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

Reduced dietary intake and reduced body weight gains and actual body weight losses were also evident for males from all treatment groups.

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

Reduced dietary intake was evident for males from all treatment groups when compared to controls and food efficiency (the ratio of body weight gain to dietary intake) was similarly reduced.

Food efficiency:

effects observed, treatment-related

Water consumption and compound intake (if drinking water study):

no effects observed

Haematological findings:

no effects observed

Description (incidence and severity):

No toxicologically significant effects were detected on the haematological parameters investigated.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

Blood chemical assessments showed increases in ALAT and ASAT when compared to controls for males treated with 1000 and 300 mg/kg bw/day. Slight reductions in A/G ratio and albumin levels were also evident for high dose males, together with increases in total protein levels.

Effect levels

Dose descriptor:

NOEL

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

food consumption and compound intake

gross pathology

haematology

histopathology: neoplastic

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

water consumption and compound intake

Remarks on result:

not determinable

Any other information on results incl. tables

The administration of TSE-1 by oral gavage for seven consecutive days at dose levels of 150, 300 and 1000 mg/kg bw/day resulted in treatment-related changes at all dose levels.

Clinical signs were mainly confined to the presence of post-dose increased salivation at all dose levels. One male treated at 1000 mg/kg bw/day showed clinical signs of ptosis, lethargy, hunched posture and respiratory pattern changes. Reduced dietary intake and reduced body weight gains and actual body weight losses were also evident for males from all treatment groups. These findings may have been suggestive of irritancy; however, histopathological examinations did not reveal any treatment-related gastric changes to support this.

Blood chemical assessments showed increases in ALAT and ASAT when compared to controls for males treated with 1000 and 300 mg/kg bw/day. Slight reductions in A/G ratio and albumin levels were also evident for high dose males, together with increases in total protein levels.

No treatment-related macroscopic abnormalities were recorded at termination, although elevated liver weights were evident for females from all treatment groups. The most noticeable finding on this study was the presence of pericholangitis (inflammation around the bile ducts) for animals from all treatment groups, suggestive of hepatotoxicity at all dose levels.

Based on the histopathological findings observed in this study, a ‘No Observed Effect Level’ (NOEL) or ‘No Observed Adverse Effect Level’ (NOAEL) could not be established.

Applicant's summary and conclusion

Conclusions:

The oral administration of TSE-1 to rats by gavage for a period of seven consecutive days at dose levels of 150, 300 and 1000 mg/kg bw/day resulted in treatment-related effects at all dose levels. Hepatotoxicity was evident at all dose levels, therefore a ‘No Observed Effect Level’ (NOEL) or ‘No Observed Adverse Effect Level’ (NOAEL) could not be established for this study.