Registration Dossier

Administrative data

Description of key information

For oral or dermal route, the acute toxicity of the registration substance is assessed as of no concern. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1991-03-04 to 1991 03-26
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Rationale for the reliability: Guideline study; well-performed and well-documented; read-across Read-across justification: the registration substance and the read-across supporting substance belong to homologous series of (Polypropenyl succinimido)- caproic acid
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
other: sesame oil
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Preliminary study; for each dose levels of 500, 1000 and 2000 mg/kg bw one male and one female rats were used. No significant effects were found.
Preliminary study:
No effect found
Sex:
male/female
Dose descriptor:
discriminating dose
Effect level:
2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality found
Clinical signs:
Within 24 hours: increased respiration rate, squatting posture, sunken flanks, stilted and uncordinated gait, decreased spantaenous activity, bristling coat
After 24 hours
Body weight:
Not impaired in the observation period of 14 days
Gross pathology:
No effect

Justification for the read-across approach using (Pentapropenyl succinimido)-caproic acid as supporting substance:

The registration substance (Tetrapropenyl succinimido)-caproic acid and proposed supporting substance (Pentapropenyl succinimido)-caproic acid are homolog series of (Polypropenyl succinimido)-caproic acid and can be considered as to belong to "chain lenght category". Similar metabolite fates and the same mode of action can be presumed.

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral toxicity of the read-across supporting substance was investigated according to the OECD Guideline 401. At dose of 2000 mg/kg bw no significant effect was found.
Executive summary:

The acute oral toxicity of the read-across supporting substance was investigated according to the OECD Guideline 401. At dose of 2000 mg/kg bw no significant effect was found. The doses provided equals 2500 mg/kg bw of the registration substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
One valid Guideline study on read-across supporting substance.

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:
2011-05-05 to 2011-05-25
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: recently performed Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: RccHanTM: WIST(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V.
- Age at study initiation: 9 or 11 weeks
- Weight at study initiation: 183.8 g – 193.5 g (females); 228.2 g – 245.7g (males)
- Fasting period before study:
- Housing: Standard Laboratory Conditions.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: Six days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12 / 12

Vehicle:
corn oil
Details on dermal exposure:
TEST SITE
- Area of exposure: 5 x 5 cm
- % coverage: 10% of the total body surface
- Type of wrap if used: surgical gauze pad

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After the 24-hour application period, the dressing was removed and the skin was flushed with
lukewarm water and drapped off with disposable paper towels.
- Time after start of exposure: 24-hour

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Concentration (if solution): 2000 mg/kg
- Constant volume or concentration used: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): 4 mL/kg
- Lot/batch no. (if required): 400 159 216
Duration of exposure:
24 Hour
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: Daily during acclimatization. Once before treatment and within the first 30 minutes and approximately 1, 2, 3 and 5 hours after treatment on test day 1 (in common with the clinical signs). Twice daily during test days 2 – 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination
Statistics:
No statistical analysis was performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No intercurrent deaths occurred during the course of the study.
Clinical signs:
No clinical signs were observed throughout the entire observation period.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Other findings:
All animals showed slight erythema from the beginning of the observation until days three or five and six. Additionally, all animals had slight focal crusts and slight desquamation on several days, in most cases during the six last days of the observation period.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of (Tetrapropenyl succinimido)-caproic acid after single dermal administration to male and female rats, observed over a period of 14 days, is: LD50(dermal) (Wistar rat): greater than 2000 mg/kg body weight
Executive summary:

The acute dermal toxicity of (Tetrapropenyl succinimido)-caproic acid was investigated according to the OECD Guideline 402. At dose of 2000 mg/kg bw, no toxicity was found.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
discriminating dose
Value:
2 000 mg/kg bw
Quality of whole database:
One valid Guideline study

Additional information

Acute oral toxicity

The acute oral toxicity assessment is performed by use of read-across approach

a) Justification for the read-across approach using (Pentapropenyl succinimido)-caproic acid as supporting substance:

The registration substance (Tetrapropenyl succinimido)-caproic acid and proposed supporting substance (Pentapropenyl succinimido)-caproic acid belong to homolog series of (Polypropenyl succinimido)-caproic acid and can be considered as to belong to a "chain lenght category". Similar metabolite fates and the same mode of action can be presumed.

b) Study Summary

(Pentapropenyl succinimido)-caproic acid was given to rats via gavage at 2000 mg/kg bw. No significant toxicity was observed. The LD50 was found higher than 2000 mg/kg bw

c) Evaluation

When the applied dose of the read-across supporting substance corresponds to ca. 1800 mg/kg bw of the registration due to the molecular mass difference. Nevertheless, an LD50 higher than 2000 mg/kg bw can be soundly derived. It is not likely that the increase of the dose level by ca. 10% would lead to significantly increased toxicity.

Acute dermal toxicity

The registration substance was given to rats dermally at 2000 mg/kg bw. No significant toxic effect was observed. The LD50 of higher than 2000 mg/kg bw was obtained.


Justification for selection of acute toxicity – oral endpoint
Guideline study; well-performed and welldocumented

Justification for selection of acute toxicity – dermal endpoint
Guideline study; well-performed and well-documented

Justification for classification or non-classification

Based on the available data the acute toxicity of the registration substance is assessed to be of no concern.

No classification is warranted.