sodium/triethanolamine- 6-(2,5-dioxo-3-C12-18-alkenyl(even and odd, branched, unsaturated)-pyrrolidin-1-yl)hexanoate

Endpoint summary

Description of key information

The single oral application of 800 mg/kg bw the registration substance did not induce any effect. Also no effect was seen after application of 2000 mg/kg bw of the acid of the registration substance. 
The acute dermal toxicity was assessed based on the data for the read-across supporting substance. No effect was observed at 2000 mg/kg bw. 

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 500 mg/kg bw

Quality of whole database:

One study on the registration substance and one study on the read-across supporting substance are available. Consistent results are obtained.

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2011-05-05 to 2011-05-25

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

Rationale for reliability of 2: Guideline study, well-performed and well-documented, read-across Justification of read-across: The acid form of the registration substance and proposed supporting substance (Tetrapropylensuccinimido)-capronic acid are homolog series of (Polypropylensuccinimido)-caproid acid.

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: RccHanTM: WIST(SPF)

Sex:

male/female

Details on test animals or test system 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.

Justification for the read-across approach using (Tetrapropylensuccinimido)-capronic acid as supporting substance:

The acid form of the registration substance and proposed supporting substance (Tetrapropylensuccinimido)-caproic acid are homolog series of (Polypropylensuccinimido)-caproic acid. These substances are produced by reaction of 6-aminocaproic acid with corresponding polypropylensuccinic anhydride. The only structural difference is that the alkyl moiety of the registratoin substance is composed of five propylen unit, whereas that of the supporting substance is composed of four propylen unit. The given structural difference is not likely to be associated with significantly deviating acute dermal toxicity, because neither the skin penetration property nor the chemical reactivity is likely to be significantly influenced by the given structural difference.

Evaluation of the acute dermal toxicity of the registration substance

The read-across supporting substance did not induce any systemic effect in the acute dermal toxicity study. Likewise no significant acute dermal toxicity for the registration substance can be derived.

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The median lethal dose of (Tetrapropylenesuccinimido)-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 the registration substance was assessed based on the read-across approach using (Tetrapropylensuccinimido)-caproic acid as read-across supporting substance.

The acute dermal toxicity of (Tetrapropylensuccinimido)-caproic acid was investigated according to the OECD Guideline 402. At dose level of 2000 mg/kg bw no systemic effect was observed.

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.

Additional information

The acute toxicity of the registration substance was assessed based on the data on the registration substance as well as the read-across supporting substances.

Justification for the read-across using (Pentapropylensuccinimido)-caproic acid as supporting substance.

The read-across supporting substance is a weak acid and the registration substance is the corresponding weak base. When dissolved in aqueous system or in the biological fluid the registration substance will be dissociated and converted in the read-across supporting substance and sodium ion/triethanolamine ammonium, thereby explaning the expected comparability. The counter ions of the registration substance, sodium ion and triethanolamine ammonium ions are of no toxicological meaning.

Upon exposure to the registration substance the conversion to the read-across supporting substance is likely to occur prior to adsorption. It means, the conversion occurs mostly already in the gastro-intestinal tract, in the fluid of the respiratory tract and during the penetration of the upper layer of epidermis for uptake routes oral, inhalative and dermal respectively.

No potency difference is expected based on the molar doses.

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

The acid form of the registration substance and proposed supporting substance (Tetrapropylensuccinimido)-caproic acid are homolog series of (Polypropylensuccinimido)-caproic acid. These substances are produced by reaction of 6-aminocaproic acid with corresponding polypropylensuccinic anhydride. The only structural difference is that the alkyl moiety of the registratoin substance is composed of five propylen unit, whereas that of the supporting substance is composed of four propylen unit. The given structural difference is not likely to be associated with significantly deviating toxicity, because neither the skin penetration property nor the chemical reactivity is likely to be significantly influenced by the given structural difference.

Acute toxicity assessment

The single oral application of 800 mg/kg bw the registration substance did not induce any effect. Also no effect was seen after application of 2000 mg/kg bw of the acid of the registration substance.

The acute dermal toxicity was assessed based on the data for the read-across supporting substance. No effect was observed at 2000 mg/kg bw.

Justification for selection of acute toxicity – oral endpoint
Two studies are of equal validity. The weight of evidence approach is used.

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.