1-acetyl-4-(3-dodecyl-2,5-dioxo-1-pyrrolidinyl)-2,2,6,6-tetramethylpiperidine

Endpoint summary

Description of key information

The LD₅₀value for acute oral toxicity in rats is > 3000 mg/kg bw. The LC₅₀ in rats was determined to be > 2.61 mg/L (4 h exposure). There are no studies on acute dermal toxicity available.

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:

1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: OECD 401 (1981)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Bor: WISW

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: F. Winkelmann, Borchen
- Females (if applicable) nulliparous and non-pregnant: yes
- Weight at study initiation: 127 g
- Fasting period before study: 16 h
- Housing: 1-5 animals in Type II Makrolon cage
- Diet (e.g. ad libitum): R10 complete feed for rats, Ssniff Spezialfutter GmbH, Soest; ad libitum
- Water (e.g. ad libitum): Tap water; ad libitum
- Acclimation period: 4-8 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20+/-1°C
- Humidity (%): 60+/-5%
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES:
From: 13.5. To: 27.5.1988

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

3000 mg/kg

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (or other?)
- Frequency of observations and weighing:
signs: up to 6 h after tretement and then daily
weighing: before treatment, 1, 7 and 14 days after treatment
- Necropsy of survivors performed: yes

Statistics:

LD50 determined according to Litchfield and Wilcoxon

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 3 000 mg/kg bw

Based on:

test mat.

Mortality:

Male: 3000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 3000 mg/kg bw; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: other: Signs of toxicity related to dose levels: No signs of toxicity were noted.

Gross pathology:

Dissection at the end of the experiment revealed no evidence of macroscopically detectable organ changes.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 of this substance was determined to be greater than 3000 mg/kg body weight.

Executive summary:

In a determination of the acute oral toxicity on male and female rats it was found that the LD50 of the substance is greater than 3000 mg/kg of body weight. The treated animals were free of signs of toxicity. There was no influence on the increase in body weight. Dissection at the end of the experiment revealed no evidence of macroscopically detectable organ damages.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

reliable without restriction

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1991

Reliability:

1 (reliable without restriction)

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

GLP compliance:

yes

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK Ltd., England
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: 6 and 8 weeks
- Weight at study initiation: 200 g
- Housing: in stainless steel cages with sheet material forming the sides and welded wire mesh forming the front, back and floor
- Diet (e.g. ad libitum): SDS RM1, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-25°C
- Humidity (%): 35-65%

IN-LIFE DATES:
From: 24.0.4 To: 14.05.1991

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

other: 80 % solution in acetone

Mass median aerodynamic diameter (MMAD):

2.7 µm

Geometric standard deviation (GSD):

2.03

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Aerosol generator
- Exposure chamber volume: approx. 120 L
- Method of holding animals in test chamber: Each chamber was divided by wire mesh partitions to provides 10 separate animal compartments. The test atmosphere entered through a port at the base centre of the chamber and passed out through small holes in the lower edge of the square section. Each chamber was positioned inside a large glass walled cabinet equipped with an extract fan exhausting to atmosphere through a collection filter.
- Source and rate of air: supply of clean dried air; 25 L/min
- System of generating particulates/aerosols: aerosol generator
- Method of particle size determination: Samples were taken using a Marple model 296 cascade impactor and the material collected on the stages was weighed and analysed chemically to determine the particle size distribution
- Treatment of exhaust air: 23-24°C


VEHICLE
- Composition of vehicle (if applicable): air


TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter): 2.7 µm +/- 2.03

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric and chemical analysis

Duration of exposure:

4 h

Remarks on duration:

Observation period 14 days post exposure

Concentrations:

Atmosphere concentration: 2.61 mg/l of air (88 % of the droplets were respirable. MMAD = 2.7 µm)

No. of animals per sex per dose:

One control group and 1 test group each of 5 male and 5 female rats.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
clinical signs: 2/day
body weight: daily
- Necropsy of survivors performed: yes
- Other examinations performed:
histopathology: lungs, liver, kidneys
- Organ weight:
lungs

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.61 mg/L air

Exp. duration:

4 h

Mortality:

Male: 2.61 mg/L; Number of animals: 5; Number of deaths: 0
Female: 2.61 mg/L; Number of animals: 5; Number of deaths: 0

Clinical signs:

other: (a) During exposure: The signs were consistent with exposure to a mildly irritant aerosol and included partial closing of the eyes, wetness around the eyes and snout and abnormal respiratory movements. (b) During the observation period: Signs observed fol

Body weight:

Reduced bodyweight or rate of bodyweight gain was seen in some male rats for 1 day following exposure.

Gross pathology:

Macroscopic pathology: No treatment-related findings.
Microscopic pathology: No treatment-related findings.

Other findings:

Food and water consumption: Food consumption was reduced in males only for 1 day following exposure to the substance. Water consumption was reduced overnight following exposure.

Lung weight to bodyweight ratio: The lung weight to bodyweight ratio for all rats exposed to the substance was considered to be within normal limits.

There were no deaths during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

For the test substance, the LC50 (4-hour) was determined to be > 2.61 mg/l of air.

Executive summary:

For the test substance, the LC50 (4-hour) was determined to be > 2.61 mg/l of air in the acute inhalation toxicity study. There were no deaths during the study. Considering pathology, no treatment-related findings were observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

reliable without restriction

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
Due to REACH Regulation, Annex VIII the performance of a third acute toxicity test beyond the already tested oral and inhalation route is not mandatory. It can reasonably be deduced that Hostavin 3058 does not exert systemic toxic effects after dermal application and thus does not have to be classified, because this substance did not cause lethal effects after administration of a single oral dose of 3,000 mg/kg bw in rats. Furthermore the substance does not have to be classified as eye irritating. Due its molecular structure it is unlikely that higher amounts (limit dose of dermal toxicity testing according OECD 402: 2,000 mg/kg bw/d) than tested in the acute oral toxicity study (tested up to 3,000 mg/kg bw/d) will be systemically available via the intact skin. Furthermore, the LC50 of an acute inhalation toxicity study was greater than 2.61 mg/L. Therefore, testing is not scientifically necessary.

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

-    Acute toxicity after single oral application was tested in male and female rats, which received a single dose of 3000 mg/kg bw. No deaths occurred.

No clinical signs were reported. The body weights were unaffected. The necropsy did not reveal any effect. The LD₅₀value for acute oral toxicity is > 3000 mg/kg bw.

- The test substance was tested for its inhalation toxicity properties. Single inhalation of the test item to rats at an atmosphere of 2.61 mg/L was associated with no mortality. The LC₅₀was determined to be > 2.61 mg/L.

- No test on acute dermal toxicity is available. But due to the available data on acute oral toxicity and taking into account the substance's physico-chemical properties it can reasonably be assumed that the substance is not acutely toxic up to the limit dose for classification after dermal application.

Justification for classification or non-classification

Due to the results on acute toxicity as described above it is concluded that Hostavin 3058 has not to be classified for acute toxicity according to Regulation (EC) No 1272/2008.