Registration Dossier

Administrative data

Description of key information

Acute toxicity, oral in rats: LD50 = 1656 mg/kg bw (equivalent or similar to OECD 401, non-GLP, K, Rel.2)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
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
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
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
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Bodyweight: 200-250 g
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.
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.

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

 

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
1 656 mg/kg bw
Quality of whole database:
Some details of the experimental conditions are missing (animal conditions, bodyweights) but the main useful data are described for appropriate hasard assessment.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: via oral route

Six groups of 10 albino rats each (5 males and 5 females) were administrated Fessoukh ethanol extract 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.

Justification for classification or non-classification

Harmonized classification:

The registered substance has no harmonized classification according to the Regulation (EC) No. 1272/2008.

Self-classification:

Acute toxicity via Oral route:

Based on the available information, the registered substance is:

- classified as category 4, "H302: Harmful if swallowed" according to Regulation EC No. 1272/2008 because the LD50 = 1656 mg/kg bw in rats

Acute toxicity via Dermal route:This information is not available

Acute toxicity via Inhalation:This information is not available.

Specific target organ toxicity: single exposure (Oral):

The classification criteria according to the Annex VI of the Regulation (EC) No. 1272/2008 as specific target organ toxicant (STOT) – single exposure, oral are not met since no reversible or irreversible adverse health effects were observed immediately or delayed after exposure and no effects were observed at the guidance value (oral) for a Category 1 classification (C ≤ 300 mg/kg bw) and at the guidance value (oral) for a Category 2 classification (2000 mg/kg bw ≥ C > 300 mg/kg bw). No classification is required.

Specific target organ toxicity: single exposure (Dermal): This information is not available

Specific target organ toxicity: single exposure (Inhalation): This information is not available.

Based on its composition (> 10% of aspiration toxicants or hydrocarbons), the registered substance is classified for aspiration hazard category 1, H304 according to CLP Regulation and GHS.