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Description of key information

Acute toxicity, oral: rat male/female LD50 > 9000 mg/kg (Pasquet, 1976); mouse male/female = 12240 mg/kg (Pasquet, 1976)

Acute toxicity, dermal: rat male/female LD50 > 9000 mg/kg (Pasquet, 1976)

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:
(no data on starting date) 30-AUG 1976 (date of report)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted before GLP principles (1976). However, study performed according to basic scientific principles acceptable for assessment although some information is missing on test conditions and on test substance composition.
Qualifier:
according to guideline
Guideline:
other: performed according to standard acute method
Deviations:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
other: CD (COBS)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Charles River, France
- Age at study initiation: no data
- Weight at study initiation: 180-230 g
- Fasting period before study: no data
- Housing: no data
- Food consumption: no data
- Water consumption: no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS:
- Temperature: no data
- Humidity: no data
- Air changes: no data
- Photoperiod: no data

IN-LIFE DATES: no data
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE:
- no vehicle
- product administered as such

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
0, 0.5 and 10 mL/kg (corresponding to 0, 4500 and 9000 mg/kg b.w.)
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> mortality and clinical signs: observation at least once daily up to the end of the 14-day observation period (day 15).
> body weights: Weighing animals daily to lethal doses
- Necropsy of survivors performed: yes (macroscopic examination of main thoracic and abdominal organs).
Statistics:
Statistical analysis for body weight gain according to Student's t test.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 9 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 5 mL/kg and only one female died at 10 mL/kg (day 5) (10%).
Clinical signs:
No symptom was noted at 5 mL/kg. Sedation and dyspnea were observed at 10 mL/kg.
Body weight:
No effect observed, all surviving animals had gained weight.
Gross pathology:
Macroscopic examination of the main organs showed no apparent abnormalities.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral LD50 value of the test item was found to be > 9000 mg/kg bw in male and female CD rats. According to the UN GHS and CLP criteria, the substance is not classified for the acute oral toxicity.
Executive summary:

CD rats (5 Males + 5 Females per dose) have been exposed by gavage at 0, 5 and 10 mL/kg of Rhodiantal IBCH (corresponding to 0, 4500 and 9000 mg/kg). Observation period: 15 days.

Results: No mortality was observed at 5 mL/kg and only one female died at 10 mL/kg (day 5) (10%). No symptom was noted at 5 mL/kg. Sedation and dyspnea were observed at 10 mL/kg.

Under the conditions of this study, the acute oral LD50 value of the test item was found to be > 10 mL/kg (corresponding to > 9000 mg/kg ) in male and female CD rats. According to the UN GHS and CLP criteria, the substance is not classified for the acute oral toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Two studies are available for the acute oral toxicity endpoint and are of good reliability (Klimisch score = 2). Furthermore, the results obtained in both studies are consistent, so that the whole dataset is considered of good quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
(no data on starting date) 30-AUG 1976 (date of report)
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted before GLP principles (1976). However, study performed according to basic scientific principles acceptable for assessment although some information is missing on test conditions and on test substance composition.
Qualifier:
according to guideline
Guideline:
other: performed according to standard acute method
Deviations:
not applicable
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD (COBS)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS:
- Source: Charles River, France
- Age at study initiation: no data
- Weight at study initiation: 180-230 g
- Fasting period before study: no data
- Housing: no data
- Food consumption: no data
- Water consumption: no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS:
- Temperature: no data
- Humidity: no data
- Air changes: no data
- Photoperiod: no data

IN-LIFE DATES: no data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
The product is applied as such to a previously shaved skin area of the back area (6x6 cm); zonne treated is then covered for 24 hours by an occlusive dressing (+ aluminum foil tape) to avoid that animals lick.

REMOVAL OF TEST SUBSTANCE
After this period, the dressing is removed and the treated area is washed with warm soapy water and then dried.

TEST MATERIAL
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

VEHICLE
- no vehicle
- product administered as such
Duration of exposure:
24 hours
Doses:
0, 10 mL/kg (corresponding to 0, 9000 mg/kg)
No. of animals per sex per dose:
10
Control animals:
yes
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
> mortality and clinical signs: observation at least once daily up to the end of the 14-day observation period (day 15).
> body weights: Weighing animals daily to lethal doses
- Necropsy of survivors performed: yes (macroscopic examination of main thoracic and abdominal organs).
Statistics:
Statistical analysis for body weight gain according to Student's t test.
Dose descriptor:
LD50
Effect level:
> 9 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed at 10 mL/kg.
Clinical signs:
No clinical signs and no skin irritation were noted.
Body weight:
Only a slight body weight decrease (5 to 8%) has been observed compared to the control group 5 days after exposure (males and females) and 10 day after exposure (males only).
Gross pathology:
No abnormality was observed at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute dermal LD50 value of the test item was found to be > 9000 mg/kg bw in male and female CD rats. According to the UN GHS and CLP criteria, the substance is not classified for the acute dermal toxicity.
Executive summary:

CD rats (10 males + 10 females per dose) have been exposed by dermal route during 24 hours at 0 and 10 ml/kg of Rhodiantal IBCH. Type of dressing: occlusive. Observation period: 15 days.

Results: No mortality was observed at 10 mL/kg, no clinical signs and no skin irritation were noted. Only a slight body weight decrease (5 to 8%) has been observed compared to the control group 5 days after exposure (males and females) and 10 days after exposure (males only). No abnormality was observed at necropsy.

Under the conditions of this study, the acute dermal LD50 value of the test item was found to be > 10 mL/kg (corresponding to > 9000 mg/kg bw) in male and female CD rats. According to the UN GHS and CLP criteria, the substance is not classified for the acute dermal toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
One study is available for the acute dermal toxicity endpoint and is of good reliability (Klimisch score = 2).

Additional information

Acute oral toxicity:

Two Klimisch score 2 studies (rat and mouse) were available for oral route. One study (rat) was used as a key study and the other one (mouse) used as supporting:

In the key study (1976), CD rats (5 Males + 5 Females per dose) have been exposed by gavage at 0, 5 and 10 mL/kg of Rhodiantal IBCH (corresponding to 0, 4500 and 9000 mg/kg). Observation period: 15 days. No mortality was observed at 5 mL/kg and only one female died at 10 mL/kg (day 5) (10%). No symptom was noted at 5 mL/kg. Sedation and dyspnea were observed at 10 mL/kg. Under the conditions of this study, the acute oral LD50 value of the test item was found to be > 10 mL/kg (corresponding to > 9000 mg/kg ) in male and female CD rats. According to the UN GHS and CLP criteria, the substance is not classified for the acute oral toxicity. The acute oral toxicity of the substance is very low.

In the supporting study (1976), OF1 mice (5 Males + 5 Females per dose) have been exposed by gavage at 0, 10, 15, 22 and 34 mL/kg of IBCH Rhodiantal (corresponding to 0, 9000, 13500, 19800 and 30600 mg/kg). Observation period: 15 days. The mortality is 0/10, 0/10, 7/10; 10/10 and 10/10 respectively at 0, 10, 15, 22 and 34 mL/kg (corresponding to 0, 9000, 13500, 19800 and 30600 mg/kg) for males and females. The mortality for females is 0/5, 0/5, 2/5; 5/5 and 5/5 respectively at 0, 10, 15, 22 and 34 mL/kg (corresponding to 0, 9000, 13500, 19800 and 30600 mg/kg). The mortality for males  is 0/5, 0/5, 5/5; 5/5 and 5/5 respectively at 0, 10, 15, 22 and 34 mL/kg (corresponding to 0, 9000, 13500, 19800 and 30600 mg/kg). Sedation with ptosis, dyspnea, diarrhoea and body weight decrease were observed at all treated doses. LD50 (for males and females) = 13.6 mL/kg (corresponding to 12240 mg/kg). LD50 (for females) = 16.2 ppm (corresponding to 14580 mg/kg). LD50 (for males) = 12.5 ppm (corresponding to 11250 mg/kg). Under the conditions of this study, the acute oral LD50 value of the test item was found to be 12240 mg/kg bw in male and female OF1 mice. Based on the lowest LD50 and according to the UN GHS and CLP criteria, the substance is not classified for the acute oral toxicity. The acute oral toxicity of the substance is very low.

 

Acute dermal toxicity:

One Klimisch score 2 study was available for dermal route and was used as a key study. In this study (1976), CD rats (10 males + 10 females per dose) have been exposed by dermal route during 24 hours at 0 and 10 ml/kg of Rhodiantal IBCH. Type of dressing: occlusive. Observation period: 15 days.

No mortality was observed at 10 mL/kg, no clinical signs and no skin irritation were noted. Only a slight body weight decrease (5 to 8%) has been observed compared to the control group 5 days after exposure (males and females) and 10 days after exposure (males only). No abnormality was observed at necropsy. Under the conditions of this study, the acute dermal LD50 value of the test item was found to be > 10 mL/kg (corresponding to > 9000 mg/kg bw) in male and female CD rats. According to the UN GHS and CLP criteria, the substance is not classified for the acute dermal toxicity. Dermal acute toxicity of the substance is very low.

Justification for classification or non-classification

Harmonized classification:

No harmonized classification is available according to the Regulation (EC) No 1272/2008.

 

Self classification:

Phenol, 2-methoxy-, reaction products with 2,2- dimethyl-3-methylenebicyclo[2.2.1]heptane, hydrogenated is not classified for acute oral toxicity according to the Regulation (EC) 1272/2008 (CLP) and according to the Directive 67/548/EEC as the oral LD50 (rat) is higher than 9000 mg/kg bw.

Phenol, 2-methoxy-, reaction products with 2,2- dimethyl-3-methylenebicyclo[2.2.1]heptane, hydrogenated is not classified for acute dermal toxicity according to the Regulation (EC) 1272/2008 (CLP) and according to the Directive 67/548/EEC as the dermal LD50 (rat) is higher than 9000 mg/kg bw.

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