Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1988-06-09 and 1988-06-16
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientific standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1988
Report Date:
1988

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A group of six rats (3 males and 3 females) was treated at 2.0 g/kg bodyweight and, based on the result of that dosing, a further group of six rats was dosed at 5.0 g/kg.
GLP compliance:
yes
Test type:
other: single dose

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Patchouli oil MD
- Physical state: clear amber liquid
- Storage condition of test material: ambient temperature in the dark

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River UK Limited, Margate, Kent, England
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 108-142 g
- Fasting: overnight prior to dosing and for approximately 4 hours after dosing.
- Housing: grouped by sex in metal cages with wire mesh floors.
- Diet: Standard laboratory rodent diet (Labsure LAD-1) ad libitum (see Appendix 1, attached)
- Water: ad libitum (see Appendix 2, attached, for results of routine chemical examination of water at source (Grafham Final Water) as conducted by Anglian Water Authority)
- Acclimation period: 8 days prior to start of study

ENVIRONMENTAL CONDITIONS
- Temperature: 21-24 ºC
- Humidity: mean value 67 %
- Air changes: approximately 15 per hour
- Photoperiod: controlled by a time switch to provide 12 hours artificial light in each 24 hour period.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The appropriate dose volume of the test substance was administered to each rat using a syringe and plastic catheter (8 choke)
Doses:
Single dose
No. of animals per sex per dose:
3 males and 3 females
Control animals:
no
Details on study design:
- Each animal was identified by cage number and ear punching.
- Each cage was identified by a coloured label displaying the dose level, study schedule number and the initials of the study director.
- Animals were observed soon after dosing and at frequent intervals for the remainder of day one (a minimum period of five hours).
- On subsequent days the animals were observed once in the morning and again at the end of the experimental day.
- The latter observation was at approximately 16:30 hours on weekdays or 11:30 hours on Saturday and Sunday.
- Clinical signs were recorded at each observation.
- All animals were observed for 14 days after dosing.
- Nature, severity, approximate time of onset and duration of each toxic sign was recorded.
- Individual bodyweights of rats were recorded on days 1, 8 and 15.
- All animals were killed on day 15 by cervical dislocation and were subjected to a macroscopic post mortem examination, which consisted of opening the abdominal and thoracic cavities.
- Macroscopic appearance of abnormal organs when present was recorded.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 other: g/kg bw
Based on:
test mat.
Mortality:
No deaths took place following administration of test material at 2.0 or 5.0 g/kg bodyweight
Clinical signs:
- All rats showed pilo-erection, abnormal body carriage (hunched posture), abnormal gait (waddling), lethergy and increased salivation within three hours of dosing (refer to Table 1, attached).
- Decreased respiratory rate was seen in all rats treated with 2.0 g/kg within four hours of dosing (refer to Table 1, attached).
- Pallor of the extremities was observed in all rats treated with 5.0 g/kg within four hours of dosing (refer to Table 1, attached).
- Diarrhoea was seen in females treated at 2.0 g/kg and in all rats treated at the high dose level within four hours of dosing (refer to Table 1, attached).
- Appearance and behaviour showed recovery to be complete by day 3.
Body weight:
- Slightly low bodyweight gains were recorded on day 8 for all males and two females at the high dose level.
- Other rats achieved anticipated bodyweight gains throughout the study.
Gross pathology:
- Terminal autopsy findings were normal.

Applicant's summary and conclusion

Conclusions:
The acute median lethal oral dose (LD50) to rats of the test material was found to be > 5.0 g/kg bodyweight.