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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to guideline method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Method: BASF-test according to internal SOP
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
3,7-Dimethyloctadien-2,6-al-1 (Citral)
Purity: >= 95 %

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Gassner

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
0.5 % aqueous CMC preparation with 2-3 drops Cremophor EL as emulsifier

VOLUME APPLIED: 20 ml/kg (highest dose), 13.63 ml/kg (6810 mg/kg dose) and 10 ml/kg (three lowest doses)
Doses:
2150, 3160, 4640, 6810 and 10000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations (clinical signs): < 15, 15 and 30 min, 1, 2, 4 and 5 h, further on daily
- Frequency of weighing: at the beginning of the experiment, on day 3 and 7 and at the end of the experiment
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 6 800 mg/kg bw
Mortality:
see Table 1
Clinical signs:
10000 mg/kg bw: the animals showed salivation, apathy, staggering, abdominal and lateral position, atony, narcotic state and no pain reflex before death.
6810 mg/kg bw: some animals showed apathy (1 h), staggering (1 h-5 h), salivation (15 min - 1 h), ruffled fur (3 d) and poor general condition (1 h-5 h).
4640-3160 mg/kg bw: sporadic appearance of staggering, ruffled fur, apathy and poor general state.
2150 mg/kg bw: nothing abnormal detected
Body weight:
For details see Table 2:
6810 mg/kg: slight decrease of the body weight at the end of the first week;
4640, 3160 and 2150 mg/kg bw: no effect
Gross pathology:
Dead animals: acute dilatation of the atriums; acute, congestive hyperemia; liver: peripheral lobule marking; intestine: atonic; thorax: sporadic hydrothorax;
Sacrificed animals: forestomach thickened, sporadic boutons, agglutinations with spleen and peritoneum

Any other information on results incl. tables

Pretest:

Mortality: 2/2 animals at 10,000 mg/kg bw, 1/2 animals at 4640 mg/kg bw, 0/2 animals at 1000, 215 or 46.4 mg/kg bw

Table 1: Mortality in main study

 Dose (mg/kg bw) No. of animals              Mortality within
     1h 24 h  48 h   7 d  14 d
 10000     5M  0/5  4/5   5/5  5/5  5/5
 5F  0/5   4/5   5/5   5/5   5/5
 6810     5M   0/5   0/5   2/5   2/5   2/5
 5F   0/5   0/5   1/5   2/5   2/5
 4640     5M   0/5   0/5   0/5   0/5   0/5
 5F   0/5  0/5    0/5   0/5  0/5 
 3160     5M   0/5   0/5   0/5   0/5   0/5
 5F   0/5   0/5   0/5   0/5   0/5
 2150     5M   0/5   0/5   0/5   0/5   0/5
 5F   0/5   0/5   0/5   0/5   0/5

Table 2: Mean body weight (male/female in g)

 Dose (mg/kg bw)  0 d  3d  7d  14d
 10000 220/160 
 6810 200/150 209/158 160/170 218/189 
 4640 200/160  210/168   209/173 224/187 
3160  200/150  223/163  209/174  243/188 
 2150 170/150  205/170 227/145  211/188

Applicant's summary and conclusion