Registration Dossier

Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
other information
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: well documented study report which meets basic scientific principles

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 5 mice per sex and dose were treated simultaneously by intraperitoneal injection with preparations of the test substance in carboxymethylcellulose containing 2-3 drops of Cremophor EL. The concentrations of these preparations were usually adjusted to achieve comparable volumes (10 ml/kg bw).
Group-wise documentation of clinical signs was performed over the 7- to 14-day study period.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Tetrahydrolinalool (THL); Substance-ID: XXVI 402
- Physical state: fluid
- Analytical purity: > 98%
- Molecular weight (if other than submission substance): 158 g/mol
- Other: pH 7
- Solubility: water: no; alcohol: yes

Test animals

Species:
mouse
Strain:
NMRI
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: average weight: male 30 g; female: 26 g
- Diet: Altromin R 1324, Altromin GmbH, Lage ad libitum
- Water: ad libitum

Administration / exposure

Route of administration:
intraperitoneal
Vehicle:
CMC (carboxymethyl cellulose)
Details on exposure:
VEHICLE
- Concentration in vehicle: Pretest: 10 %, 46.4%, 100% Main Test: 3.16%, 4.64%, 6.81%, 10%
- Amount of vehicle: 10 ml/kg bw

MAXIMUM DOSE VOLUME APPLIED:10 ml/kg body weight

DOSAGE PREPARATION (if unusual): administered in 0,5 % in aquous
Carboxymethyl cellulose solution with 2 to 3 drops of Cremophor EL
Doses:
316, 464, 681, 1000 µl/kg bw:
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations of clinical symptoms: < 15 min, 15 min, 30 min, 1 h, 2 h, 4 h, 5 h; d1-d14 once per day on working days
- Necropsy of survivors performed: yes
- Frequency of weighing: day 3, 7 , 10

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 0.55 mL/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
455 mg/kg bw
Remarks on result:
other: calculated with a density of 0.827 - 0.828 g/cm³
Clinical signs:
Dyspnoea, apathy, abdominal and lateral position, staggering, paresis of hindlimbs, partially atonia, partially sedate-like state with loss of cornea and pain reflex, partially rolling-and-stretching convulsions, partialy tonic and clonic spasms, exsiccosis, poor general condition, late cases of death, partially weight loss at the beginning of study
Body weight:
mean body weight:
dose 1000 µl/kg bw: male: day3: 26 g;
dose 1000 µl/kg bw: female: day3: 23 g; day 7: 25 g; day 10: 28 g;
dose 681 µl/kg bw: male: day3: 30 g, day 7: 34 g, day 10: 34 g;
dose 681 µl/kg bw: female: day3: 23 g; day 7: 27 g; day 10: 28 g;
dose 464 µl/kg bw: male: day3: 29 g, day 7: 31 g, day 10: 33 g;
dose 464 µl/kg bw: female: day3: 27 g; day 7: 29 g; day 10: 31 g;
dose 316 µl/kg bw: male: day3: 33 g, day 7: 34 g, day 10: 35 g;
dose 316 µl/kg bw: female: day3: 27 g; day 7: 28 g; day 10: 29 g;
Gross pathology:
In two mice (dose 1000 µl/kg bw) intraabdominal precipitation of substance was detected.
Other findings were not reported.

Any other information on results incl. tables

Mortality:

Pretest:

100 %: 5/5 female + 5/5 male animals after 30 min

46.4 %: 2/2 male animals after 15 min

10%: 2/2 male animals after 1h/3d

Main test:

dose (µl/kg bw) concentration (%) number of animals mortality within
1 h 24 h 48 h 7 d 14 d
1000 10 5 M 0/5 2/5 4/5 5/5 5/5
5 F 0/5 0/5 1/5 3/5 4/5
681 6.81 5 M 0/5 2/5 2/5 4/5 4/5
5 F 0/5 1/5 1/5 1/5 2/5
464 4.64 5 M 0/5 0/5 1/5 3/5 3/5
5 F 0/5 1/5 1/5 1/5 1/5
316 3.16 5 M 0/5 0/5 0/5 0/5 0/5
5 F 0/5 0/5 0/5 0/5 0/5

Applicant's summary and conclusion