Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2001

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Specific details on test material used for the study:
Fessoukh, bought from a herbalist in Rabat, was dissolved in absolute ethanol, then filtered and evaporated to dryness to obtain the resinous gum or fessoukh extract

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Bodyweight: 200-250 g

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
The total volume administered to each animal did not exceed 0.5 mL/100 g bw
Doses:
500, 1000, 1500, 2000, or 3000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
All animals were observed daily for 15 days, and deaths or any other toxic effect were noted
Statistics:
The probit method for LD50 calculation was used.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 656.1 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 576 - <= 1 740.4
Mortality:
See results table; at 3000 mg/kg, deaths occurred within 24 h after administration. At lower doses, deaths of rats began after 4 days.
Clinical signs:
Rats that survived more than 4 days had bleeding from nose, eyes, and anal and genital organs. The affected rats first had diarrhea on the 1st and 2nd day after dosing and then bleeding on days 2 and 3. The animals then had anemia and ataxia, and the last died the 7th day after dosing.
Body weight:
No data
Gross pathology:
No bleeding evidence was detected at necropsy.
Other findings:
The toxicity of the test item would be mainly due to its 4-hydroxicoumarins.

Any other information on results incl. tables

Table 1: Oral acute toxicity of fessoukh extract in rats:

 Dose (mg/kg bw)  500  1000  1500  2000  3000

 Mortality (%)

 0

 10

 30

 70

 100

 

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The LD50 of Fessoukh extract with absolute ethanol in rats is 1656 mg/kg bw therefore it is classified as category 4, "H302: Harmful if swallowed" according to Regulation EC No. 1272/2008.
Executive summary:

Six groups of 10 albino rats each (5 males and 5 females) were administrated Fessoukh extract with absolute ethanol at doses of 500, 1000, 1500, 2000, or 3000 mg/kg bw. The control group was given peanut oil only, which was used as the vehicle. All animals were observed daily for 15 days, and deaths or any other toxic effect were noted.

At 3000 mg/kg, deaths occurred within 24 h after administration. At lower doses, deaths of rats began after 4 days. Rats that survived more than 4 days had bleeding from nose, eyes, and anal and genital organs. The affected rats first had diarrhea on the 1st and 2nd day after dosing and then bleeding on days 2 and 3. The animals then had anemia and ataxia, and the last died the 7th day after dosing.

The calculated LD50 was 1656.1 mg/kg bw, with a 95% confidence limit of 1576.0 to 1740.4 mg/kg therefore the test item is classified as category 4, "H302: Harmful if swallowed" according to Regulation EC No. 1272/2008.