Registration Dossier

Toxicological information

Acute Toxicity: oral

Currently viewing:

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
study conducted similarly to OECD Guideline 401 but with a limited observation period (24 hours only)
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
abstract
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Principles of method if other than guideline:
15 adult rats of both sexes were equally divided into five groups. The first group was used as control (untreated). The second and third groups were given 50 and 100 mg/kg body weight per day of C. molmol, respectively. Doses were given for up to 14 successful days.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
"Wister albino"
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Females (if applicable) nulliparous and non-pregnant: not reported
- Age at study initiation: 3-4 months
- Weight at study initiation: 150-250 g, The mean weight of rats have been estimated from 10 randomly selected rats and was found to be 198.0 g
- Fasting period before study: not reported
- Housing: Rats were divided into five individuals for each group and allocated randomly in separate clean and well ventilated cages.
- Diet : standard pellet diet purchased from ARASCObCompany, KSA.
- Water : The drinking water for treated animals mixed with the required doses of test substance, ad labium
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C.
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark cycle

IN-LIFE DATES: no reported
Route of administration:
oral: drinking water
Vehicle:
water
Details on oral exposure:
Depending on the fact that the mean water consumption of rats is 25 ml/day, the required doses have been calculated according to the followings:
Given dose = [ Required dose (mg) × Mean weight of rats (g) ] / 1000 (g)
Accordingly, the amount of plant powders that should be suspended in rat's drinking water (per liter) has been calculated as the following equation:
Amount = [ Dose × 1000 ml ] / 25 ml
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
14 successful days
Frequency of treatment:
Exposure via drinking water
Dose / conc.:
50 mg/kg bw/day (nominal)
Dose / conc.:
100 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5 animals / group (male and female)
Control animals:
yes
Positive control:
no
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: once pre-treatment and once thereafter at termination

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Immediately after dissection
- Anaesthetic used for blood collection: No. Animals were euthanized with diethyl ether before collecting blood
- Animals fasted: Not specified
- How many animals: All (5/group)
- Parameters: white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), red cell distribution width (RDW), platelets (PLT) and mean platelet volume (MPV).

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Immediately after dissection
- Animals fasted: Not specified
- How many animals: All
- Parameters: Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Asparate aminotransferase (AST), Creatinine (CRE), Urea (BUN), glucose (GLU), Na+, K+, Ca+2 and Cl-.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No
Sacrifice and pathology:
GROSS PATHOLOGY: No

HISTOPATHOLOGY: No
Statistics:
Results were presented as mean ± S.E.M. One way analysis of variance (ANOVA) was used to determine significance between tests and controls. P-values less than 0.05 were considered significant.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
- significant increase of WBC
CONCLUSION: no adverse effects
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no adverse effects observed

Table 7.5.1/1: Mean rat's body weight after 14 days treatment

Plant Dose
mg/kg/day
Pre-treatment (g) Post-treatment (g)
C. molmol 50 190.4± 11.7 259.4±18.7
100 207.1± 11.5 266.7±9.5
control 0 196.8± 9.5 268.4± 23.1

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

Table 7.5.1/2: Hematological studies on rats after 14 days treatment

Plant Dose
mg/kg/day
WBC
(×103/µl)
RBC
(×106/µl)
HGB
(g/dl)
HCT
(%)
MCV
(fl)
MCH
(pg)
MCHC
(g/dl)
RDW
(%)
PLT
(x103/µl)
MPV
(fl)
C. molmol 50 18.4± 1.0 8.6± 0.4 15.8± 0.9 49.4± 2.3 57.1± 0.6 18.3± 0.3 32.1± 0.3 14.7± 0.9 689.8± 46.0 9.3± 0.3
100 19.4± 1.6 8.2± 0.4 15.4± 0.9 47.0± 3.1 56.4± 1.6 18.6± 0.3 32.9± 0.3 14.3± 0.2 755.8± 19.8 8.9± 0.3
control 0 12.2± 0.7 7.8± 0.4 14.8± 0.6 45.3± 1.7 58.0± 1.3 19.0± 0.3 32.7± 0.3 14.7± 0.3 757.0± 58.3 9.4± 0.5

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

Table 7.5.1/3: Biochemical studies on rats after 14 days treatment

Plant Dose
mg/kg/day
GLU
mmol/l
BUN
mmol/l
CRE
Umol/l
AST
U/l
ALT
U/l
ALP
U/l
Na+
mmol/l
K+
mmol/l
CA2+
mmol/l
Cl-
mmol/l
C. molmol 50 16.9± 1.8 6.5± 0.4 53.4± 3.5 158.6± 1.4 91.2± 14.4 441.6± 68.7 142± 1,3 10.5± 1.0 3.4± 0.1 94.4± 0.6
100 17.7± 1.7 5.9± 0.2 57.8± 3.5 150.4± 21.4 98.4± 21.3 589.4± 44.7 143.4± 0.9 11.1± 1.0 3.4± 0.1 95.0± 1.0
control 0 15.0± 1.9 6.6± 0.6 55.2± 2.2 150.2± 15.8 72.6± 9.2 319.2± 12.5 143.2± 0.9 9.75± 0.9 3.3± 0.04

95.0± 0.6

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

The mean body weights exhibited insignificant variations compared to the control group. Besides, no toxic symptoms or death were observed and they survived being active and healthy up to 14 days. These findings could be a good indicator for non-toxicity and safety of those plants at the doses of 50 and 100 mg/kg body weight per day. This assumption is supported by hematological and biochemical analysis which revealed no significant clinical changes. The interested finding is that the mean WBC counts increased significantly in rats administered C. molmol suspension. This means that C. molmol may activate the defense mechanism.

Conclusions:
Under the test conditions, the NOAEL was concluded to be 100 mg/kg bw/day in rats.
Executive summary:

In a 14 days dose toxicity study, the toxicological effects of aqueous suspensions of the resin of Commiphora molmol on Wister albino rats were studied. Two groups of each five animals were treated with 50 and 100 mg/kg/day by drinking water for 14 consecutive days. The mean body weights, hematological and biochemical analysis were evaluated.

The mean body weights exhibited insignificant variations compared to the control group. Besides, no toxic symptoms or death were observed and they survived being active and healthy up to 14 days. These findings could be a good indicator for non-toxicity and safety of those plants at the doses of 50 and 100 mg/kg body weight per day. This assumption is supported by hematological and biochemical analysis which revealed no significant clinical changes. The interested finding is that the mean WBC counts increased significantly in rats administered C. molmol suspension. This means that C. molmol may activate the defense mechanism.

Under the test conditions, the NOAEL was concluded to be 100 mg/kg bw/day in rats.

Reason / purpose:
reference to same study
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Remarks:
Study performed similarly to the OECD TG 407 with major deviations (only weight, haematology and biochemistry investigations were performed)
Reason / purpose:
reference to same study
Reason / purpose:
reference to same study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity in Rodents)
Deviations:
yes
Remarks:
number of animals per group, age of animals, absence of satellite group; only weight, hematological and biochemical examination
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
"Wister albino"
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Females (if applicable) nulliparous and non-pregnant: not reported
- Age at study initiation: 3-4 months
- Weight at study initiation: 150-250 g, The mean weight of rats have been estimated from 10 randomly selected rats and was found to be 198.0 g
- Fasting period before study: not reported
- Housing: Rats were divided into five individuals for each group and allocated randomly in separate clean and well ventilated cages.
- Diet : standard pellet diet purchased from ARASCObCompany, KSA.
- Water : The drinking water for treated animals mixed with the required doses of test substance, ad labium
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C.
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark cycle

IN-LIFE DATES: no reported
Route of administration:
oral: drinking water
Vehicle:
water
Details on oral exposure:
Depending on the fact that the mean water consumption of rats is 25 ml/day, the required doses have been calculated according to the followings:
Given dose = [ Required dose (mg) × Mean weight of rats (g) ] / 1000 (g)
Accordingly, the amount of plant powders that should be suspended in rat's drinking water (per liter) has been calculated as the following equation:
Amount = [ Dose × 1000 ml ] / 25 ml
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
28 successful days
Frequency of treatment:
Exposure via drinking water, i.e. several times per day
Dose / conc.:
250 mg/kg bw/day (nominal)
Dose / conc.:
500 mg/kg bw/day (nominal)
Dose / conc.:
1 000 mg/kg bw/day (nominal)
No. of animals per sex per dose:
5 animals / group (male and female)
Control animals:
yes
Details on study design:
- Dose selection rationale: No preliminary study was performed to determine the dose selection for the 28-days study. However, a 14-days treatment study was performed. The animals were treated with 50 and 100 mg/kg bw/d. No clinical signs, no death, and no significant variation of hematological and biochemical parameters were observed.
Positive control:
no
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Not specified

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: once pre-treatment and once thereafter at termination

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Not specified

OPHTHALMOSCOPIC EXAMINATION: Not specified

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Immediately after dissection
- Anaesthetic used for blood collection: No. Animals were euthanized with diethyl ether before collecting blood
- Animals fasted: Not specified
- How many animals: All (5/group)
- Parameters: white blood cells (WBC), red blood cells (RBC), hemoglobin (HGB), hematocrit (HCT), mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC), red cell distribution width (RDW), platelets (PLT) and mean platelet volume (MPV).

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Immediately after dissection
- Animals fasted: Not specified
- How many animals: All
- Parameters: Alkaline phosphatase (ALP), Alanine aminotransferase (ALT), Asparate aminotransferase (AST), Creatinine (CRE), Urea (BUN), glucose (GLU), Na+, K+, Ca+2 and Cl-.

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

IMMUNOLOGY: No
Sacrifice and pathology:
GROSS PATHOLOGY: No

HISTOPATHOLOGY: No
Statistics:
Results were presented as mean ± S.E.M. One way analysis of variance (ANOVA) was used to determine significance between tests and controls. P-values less than 0.05 were considered significant.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
significant decrease in mean body weights
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not examined
Haematological findings:
effects observed, treatment-related
Description (incidence and severity):
no significant differences, only the mean MPV revealed significant increase when compared to the control group
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
- decrease of serum glucoses (not-fasting)
- significant decrease of Cl-
- significant increase of CRE and BUN
- significant increase of AST
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Immunological findings:
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Neuropathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
haematology
clinical biochemistry
Key result
Critical effects observed:
no

Table 7.5.1/1: Mean rat's body weight after 28 days treatment

Plant Dose
mg/kg/day
Pre-treatment (g) Post-treatment (g)
C. molmol 250 178.6± 13.5 275.4± 13.4
500 178.0± 6.1 266.4± 7.1
1000 192.1± 15.6 236.1± 15.6
control 0 196.8± 9.5 324.5± 13.6

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

Table 7.5.1/2: Hematological studies on rats after 28 days treatment

Plant Dose
mg/kg/day
WBC
(×103/µl)
RBC
(×106/µl)
HGB
(g/dl)
HCT
(%)
MCV
(fl)
MCH
(pg)
MCHC
(g/dl)
RDW
(%)
PLT
(x103/µl)
MPV
(fl)
C. molmol 250 12.9± 2.1 8.1± 0.3 15.9± 0.3 47.3± 2.3 58.0± 0.6 19.5± 0.4 33.7± 0.3 14.6± 0.5 659.8± 64.2 8.2± 0.3
500 11.6± 2.1 8.0± 0.3 14.5± 0.6 44.3± 1.8 54.9± 1.4 18.0± 0.3 32.7± 0.4 14.7± 0.4 728.4± 54.9 7.7± 0.4
1000 9.9± 1.5 7.7± 0.4 14.7± 0.5 43.4± 1.8 56.1± 0.9 19.1± 0.4 33.9± 0.3 14.0± 0.2 756.4± 43.5 8.2± 0.4
control 0 12.2± 0.7 7.8± 0.4 14.8± 0.6 45.3± 1.7 58.0± 1.3 19.0± 0.3 32.7± 0.3 14.7± 0.3 757.0± 58.3 9.4± 0.5

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

Table 7.5.1/3: Biochemical studies on rats after 28 days treatment

Plant Dose
mg/kg/day
GLU
mmol/l
BUN
mmol/l
CRE
Umol/l
AST
U/l
ALT
U/l
ALP
U/l
Na+
mmol/l
K+
mmol/l
CA2+
mmol/l
Cl-
mmol/l
C. molmol 250 11.8± 1.4 5.7± 0.1 50.2± 2.7 167.2± 34.7 91.6± 12.8 308.4± 43.5 142.4± 1.2 10.9± 1.0 3.3± 0.1 93.8± 0.8
500 10.7± 1.2 7.6± 0.4 60.4± 2.2 195.8± 5.3 100.4± 16.8 312.2± 36.3 140.6± 0.6 11.2± 1.0 3.5± 0.1 90.2± 0.5
1000 8.5± 0.6 9.3± 0.7 61.0± 2.8 225.6± 26.3 102.6± 22.0 316.0± 36.3 141.2± 1.2 11.4± 0.7 3.3± 0.1 91.8± 0.5
control 0 15.0± 1.9 6.6± 0.6 55.2± 2.2 150.2± 15.8 72.6± 9.2 319.2± 12.5 143.2± 0.9 9.75± 0.9 3.3± 0.04 95.0± 0.6

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

The treatment results of either C. molmol suspensions revealed significant decrease in mean body weights, which may be a preliminary and sensitive index of toxicity after exposure to toxic substances. However, no toxic symptoms or deaths were found and they survived being active and healthy for up to 28 days.

The hematological analysis results of the rat groups administered C. molmol suspension exhibited no significant differences, only the mean MPV revealed significant when compared to the control group.

The biochemical parameters of rat’s serum revealed significant differences between the test and control group. The decrease of serum glucoses (not-fasting) may be due to alternation in carbohydrate metabolism. Cl- were significantly decreased, CRE and BUN exhibited significant increase, which could be an indicator for the negative impact on kidney functions. Kidney functions were evaluated by means of serum urea and creatinine levels. AST were significantly increased, implying negative impact on liver functions. The two enzymes mainly associated with hepatocellular damage in liver are AST and ALT. However, AST is present in a wide variety of tissues including heart, skeletal muscles, kidney, brain and liver. Therefore, the significant increase of AST in rats treated with C. molmol may be due to the release of enzymes from the cells of the affected organs, or to change in cell membrane permeability. Other biochemical parameters showed insignificant differences in comparison with the control group.

Conclusions:
Under the test conditions, the NOAEL can be concluded to be 500 mg/kg bw/day in rats
Executive summary:

In a repeated dose toxicity study, the toxicological effects of aqueous suspensions of the resin of C. molmol on Wister albino rats were studied. Three groups of each five animals were treated with 250, 500 and 1000 mg/kg/day by drinking water for 28 consecutive days. The mean body weights, hematological and biochemical analysis were evaluated.

The treatment results of either C. molmol suspensions revealed significant decrease in mean body weights, which may be a preliminary and sensitive index of toxicity after exposure to toxic substances. However, no toxic symptoms or deaths were found and they survived being active and healthy for up to 28 days.

The hematological analysis results of the rat groups administered C. molmol suspension exhibited no significant differences, only the mean MPV revealed significant when compared to the control group.

The biochemical parameters of rat’s serum revealed significant differences between the test and control group. The decrease of serum glucoses (not-fasting) may be due to alternation in carbohydrate metabolism. Cl- were significantly decreased, CRE and BUN exhibited significant increase, which could be an indicator for the negative impact on kidney functions. Kidney functions were evaluated by means of serum urea and creatinine levels. AST were significantly increased, implying negative impact on liver functions. The two enzymes mainly associated with hepatocellular damage in liver are AST and ALT. However, AST is present in a wide variety of tissues including heart, skeletal muscles, kidney, brain and liver. Therefore, the significant increase of AST in rats treated with C. molmol may be due to the release of enzymes from the cells of the affected organs, or to change in cell membrane permeability. Other biochemical parameters showed insignificant differences in comparison with the control group.

The treatment results of C. molmol suspensions revealed significant decrease in mean body weights, beside variations in some hematological and biochemical parameters, particularly at high doses.

Under the test conditions, the NOAEL can be concluded to be 500 mg/kg bw/day in rats.

The test material is therefore not classified for damage to organs through prolonged oral repeated exposure according to the criteria of the Annex VI of the Regulation (EC) No. 1272/2008 (CLP).

Data source

Reference
Reference Type:
publication
Title:
Toxicological assessment of the oleo-gum resins of Commiphora molmol and Boswellia papyrifera in rats
Author:
Abdallah et al.
Year:
2009
Bibliographic source:
Journal of Medicinal Plants Research Vol. 3(6), pp. 526-532, July, 2009

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1987
Deviations:
yes
Remarks:
2 test groups, sex allocation per groups is not known, 24h observation period, no details on composition of the test substance
GLP compliance:
not specified
Remarks:
this information is not reported in the publication
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Name: C. Molmol
- Source: purchased from traditional medicine shops from Al Rass town, Saudi Arabia

Test animals

Species:
rat
Strain:
Wistar
Remarks:
"Wister albino rats"
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Females (if applicable) nulliparous and non-pregnant: not reported
- Age at study initiation: 3-4 months
- Weight at study initiation: 150-250 g, The mean weight of rats have been estimated from 10 randomly selected rats and was found to be 198.0 g
- Fasting period before study: not reported
- Housing: Rats were divided into five individuals for each group and allocated randomly in separate clean and well ventilated cages.
- Diet : standard pellet diet purchased from ARASCObCompany, KSA.
- Water : The drinking water
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 ± 2°C.
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark cycle

IN-LIFE DATES: no reported

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: not reported. The required doses of the plant’s resins were suspended in 5 ml distilled water and administered orally using long-mouth syringe.
- Amount of vehicle (if gavage): 5 mL
- Justification for choice of vehicle: not reported

MAXIMUM DOSE VOLUME APPLIED: not reported
Doses:
1000 and 5000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 24h
- Frequency of observations and weighing: observations at least after 6h and 24h
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs, body weight: once before treatment and thereafter at termination, other: hematological and biochemical analysis
Statistics:
Results were presented as mean ± S.E.M. One way analysis of variance (ANOVA) was used to determine significance between tests and controls. P-values less than 0.05 were considered significant.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
other: test material in suspension
Mortality:
none reported
Clinical signs:
- 1000 and 5000 mg/kg bw: after 6h, a symptom of weakness and decrease in moving activity is observed. These symptoms increased on the next day.
Reduction in motion activity and weakness observed may be due to the fragrant resins and volatile oils and other princeples of C. molmol which may affect the central nervous system.
Other findings:
The hematological and biochemical parameters of the rat groups that administered high-dose oral single dose of either C. molmol suspensions exhibited serous significant variations. It is known that at higher concentrations, the toxic effects become manifest owing to the physiopharmacological interactions. Animals that administered C. molmol suspension showed significant increase in MCH and MCHC. While RDW and MPV showed significant decrease, while other hematological parameters were insignificant. As well, the biochemical analysis results revealed significant increase in BUN and K+ ions, beside significant decrease in Na+ and Ca+2 ions, whereas other biochemical parameters were insignificant in comparison with the control group.

Any other information on results incl. tables

Table 7.2.1/1: Hematological studies on rats after single dose treatment

Plant Dose
mg/kg/day
WBC
(×103/µl)
RBC
(×106/µl)
HGB
(g/dl)
HCT
(%)
MCV
(fl)
MCH
(pg)
MCHC
(g/dl)
RDW
(%)
PLT
(x103/µl)
MPV
(fl)
C. molmol 1000 9.9±0.9 8.7± 0.4 15.7± 0.5 48.8± 1.9 55.0± 0.6 18.0± 0.2 32.2± 0.2 15.4± 0.9 876.8± 119.1 6.9± 0.1
5000 8.4± 1.0 8.8± 0.1 16.7± 0.2 50.6± 0.9 58.0± 0.3 19.4± 0.1 33.5± 0.2 12.3± 0.4 924.0± 95.3 6.3± 0.1
control 0 12.2± 0.7 7.8± 0.4 14.8± 0.6 45.3± 1.7 58.0± 1.3 19.0± 0.3 32.7± 0.3 14.7± 0.3 757.0± 58.3 9.4± 0.5

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

Table 7.2.1/2: Biochemical studies on rats after single dose treatment

Plant Dose
mg/kg/day
GLU
mmol/l
BUN
mmol/l
CRE
Umol/l
AST
U/l
ALT
U/l
ALP
U/l
Na+
mmol/l
K+
mmol/l
CA2+
mmol/l
Cl-
mmol/l
C. molmol 1000 10.3±1.6 9.8± 1.5 43.2± 2.9 184.4± 9.8 70.6± 16.2 247.4± 38.0 126.2± 2.5 19.4± 1.6 2.67± 0.02 92.8± 1.3
5000 13.6± 2.6 11.5± 3.0 49.2± 5.1 162.5± 17.3 84.0± 14.8 357.2± 44.1 127.0± 3.0 21.5± 2.3 2.81± 0.05 94.2± 1.1
control 0 15.0± 1.9 6.6± 0.6 55.2± 2.2 150.2± 15.8 72.6± 9.2 319.2± 12.5 143.2± 0.9 9.75± 0.9 3.3± 0.04 95.0± 0.6

Data presented as mean ± S.E.M., n = 5, significantly different from control: P < 0.05.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Oral LD50 > 5000 mg/kg bw
Executive summary:

In an acute oral toxicity study performed similarly to OECD Guideline 401, groups of Wister albino rats (5/dose) were administered a single oral dose of aqueous suspensions of the resin of Commiphora molmol at 1000 or 5000 mg/kg bw/day. Animal were then observed for mortality, clinical signs, body weights, hematological and biochemical analysis for one day.

No mortality was reported during the 24h observation period. Weakness and decrease in motion activity were observed at 5000 mg/kg bw in addition to significant variations in some hematological and biochemical parameters compared to the control group.

The acute oral LD50 is considered to be higher than 5000 mg/kg bw.

Under the test conditions, the substance is not classified for acute oral toxicity according to the annex VI of the Regulation EC No. 1272/2008 (CLP) and to the GHS.