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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline, GLP study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Report Date:
2001

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.7 (Repeated Dose (28 Days) Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsors identification LIPACIDE 0G
Description off white soli d
l3atch numbcr : 00 171 300
Date reccived 01 August 2000
Storagc conditions room temperature. in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Six male and six female Spraguc-Dawley Cri:CD (SI)) f05 BR strain rats were obtained from Charles River (UK) Limited, Margate, Kent. Afier an acclimatisation period of at icast seven days, animais were sclected at random and given a unique number within the study by ear punching.

At the start of treatment the maies weighed 163 w 210 g and the females weighed 152 to 170 g. The animais were housed in groups of three by sex in polypropylene grid-floor cages suspended over trays containing absorbent paper. F’ree access to mains drinlcing water and food (Rat and Mouse SQC Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK) was allowed throughout thc study

The animais were housed in a single air-conditioned room within the Safepharm Ranier Maintaincd Rodent Facility. Thc rate of air exchange was at least fifieen air changes per hour and the low intensity fluorescent lighting was con trolled to givc twelve hours continuous light and tweive hours darkness. Environmental conditions were continuously monitored hy a computerised system, and printo uts of the mean ternperature and humidities were included in the study records. The temperature and relative humidity were controlied to reniain within target ranges of 21 ± 2°C and 55 ± 15% respectiveiy. Environmental enrichment was provided in the form of wooden chew blocks (B & K Uni’icrsal Lt&, Huil, UK).

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
The test material was administered daily, for fourtecn consecutive days, by gavage using a stainicss steei cannula attached to a disposabie plastic syringe- Control animais were treated in an identical mariner with 4 ml/kg/day ofArachis ou ftP.
Duration of treatment / exposure:
14 days (preliminary study)
Frequency of treatment:
daily
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0 mL/ kg bw/day
Basis:
actual ingested
Remarks:
Doses / Concentrations:
1000 mg/ kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
6
Control animals:
yes, concurrent vehicle
Details on study design:
The test material was administered daily, for fourtecn consecutive days, by gavage using a stainicss steei cannula attached to a disposabie plastic syringe- Control animais were treated in an identical mariner with 4 ml/kg/day ofArachis ou ftP.
fle volume of test and control materiai administered to each animai was bascd on the most recent bodywcight and was adjusted at Days 4, 8 and Il.

Examinations

Observations and examinations performed and frequency:
Ail animais were examined for overt signs of toxicity, iii heaith or behavioural change im.mediateiy before dosing and one hour aftcr dosing. Ail observations wcrc recorded.
Sacrifice and pathology:
On compiction of the dosing period, ail animais were killed by cervical dislocation and immediately subjected to an internai and externai macroscopic examination. No tissues were retained.
Other examinations:
Individu.al bodyweights were recorded on Days 1, 4, 8, 11 and 14 ofthe study.

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
Ail animais treated with 1000 mg/kg/day showed thiekening of the non-glandular gastrie epithelium at terminai kilI.
Details on results:
Ciinically observable signs in treated animais were noted frorn Day 2 and included increased salivation prior to or up to ten minutes afler dosing. Hunched posture and noisy respiration were apparent during the second week of treatment together with incidents of gasping respiration and
wet Fur.

Effect levels

Dose descriptor:
dose level: 1000
Effect level:
1 000 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: highest dose for the main study

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
The dose levels for te main twenty-eight day study were ehosen, following consultation with te Sponsor, as:
High dose: 1000 mg/kg/day
Tntermediate dose: 150 mg/kg/day
Low dose: 15 mg/kg/day
plus a eontrol group treated with vehicie alone
Executive summary:

The dose levels for te main twenty-eight day study were ehosen, following consultation with te Sponsor, as: High dose: 1000 mg/kg/day Tntermediate dose: 150 mg/kg/day Low dose: 15 mg/kg/day plus a eontrol group treated with vehicie alone