N,N'-propane-1,3-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionamide]

Endpoint summary

Description of key information

Oral: Scientifically valid study; rat LC50 >10000 mg/kg. Reliability = 2

Inhalation: No study available

Dermal: equivalent to OECD 402; rat LD50 >2000 mg/kg for read-across substance. Reliability = 2

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

no guideline followed

Principles of method if other than guideline:

The acute oral LD50 of the test substance was studied in rats.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Tif: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ciba-Geigy
- Females (if applicable) nulliparous and non-pregnant: not reported
- Age at study initiation: not reported
- Weight at study initiation: 160-180 g
- Fasting period before study: yes
- Housing: animals were housed in groups of 5 in Macrolon cages (type 3)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum of 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±1°C
- Humidity (%): 55±5%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 10 hour light

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE: 2% carboxymethyl cellulose

DOSAGE PREPARATION (if unusual): The test material was suspended with 2% carboxymethyl cellulose. Before treatment the suspension was homogeneously dispersed with and Ultra-Turrax and during treatment it was kept stable with a magnetic stirrer.

Doses:

1000, 2150, 3170, 4640, 7750, 10000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Physical condition and rate of deaths were monitored throught the observation period.
- Necropsy of survivors performed: yes

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 10 000 mg/kg bw

Based on:

test mat.

Mortality:

No animlas died during the study.

Clinical signs:

other: Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 to 9 days.

Gross pathology:

No substance related gross organ changes were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (rat): >10000 mg/kg

Executive summary:

The acute oral LD50 of the test substance was observed in male and female rats over a period of 14 days. Rats were tested at doses at 1000, 2150, 3170, 4640, 7750, and 10000 mg/kg. No deaths occurred during the study. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 to 9 days. The LD50 was determined to be >10000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

10 000 mg/kg bw

Quality of whole database:

Scientifically valid study.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

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:

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

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Additional documentation, provided within the IUCLID Assessment Reports (Section 13), supports the read-across approach.

Reason / purpose for cross-reference:

read-across: supporting information

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

limited details; no necropsy performed

GLP compliance:

no

Test type:

standard acute method

Limit test:

yes

Species:

rabbit

Strain:

New Zealand White

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: not reported
- Weight at study initiation: average of 2933 g
- Fasting period before study: not reported
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23±2°C
- Humidity (%): 55±5%
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 14 hours light/day

Type of coverage:

occlusive

Vehicle:

other: 1% gum arabic in tap water

Details on dermal exposure:

TEST SITE
- Area of exposure: 200-300 cm2
- Fur was clipped prior to exposure

REMOVAL OF TEST SUBSTANCE
- Washing (if done): surface was washed with lukewarm water and a sponge
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):2.5 mL/kg

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 males

Control animals:

no

Details on study design:

- Duration of observation period following administration: 8 days
- Frequency of observations and weighing: animal weights at the beginning and end of the study were reported; frequency of observations was not reported
- Necropsy of survivors performed: no
- The Draize method was followed.

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

not reported

Other findings:

No cutaneous findings were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

LD50 (rabbit): >2000 mg/kg

Executive summary:

An acute dermal toxicity study was performed. Three male rabbits were exposed to the test substance dermally at 2000 mg/kg for 24 hours under occlusive conditions. No mortality, clinical signs, or cutaneous reactions were observed. The LD50 in rabbits was >2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Scientifically valid study.

Additional information

The acute oral LD50 of the test substance was observed in male and female rats over a period of 14 days. Rats were tested at doses at 1000, 2150, 3170, 4640, 7750, and 10000 mg/kg. No deaths occurred during the study. Within 2 hours after treatment the rats in all dosage groups showed sedation, dyspnoea, exophthalmos, curved position and ruffled fur. The animals recovered within 8 to 9 days. The LD50 was determined to be >10000 mg/kg.

 

No acute dermal study with the test substance is available. Results from an acute dermal toxicity study with N,N'-hexane-1,6-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenylpropionamide] were used as read across to fulfil the data gap for the test substance. The underlying hypothesis supporting read-across from the source (N,N'-hexane-1,6-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenylpropionamide]; CAS 23128-74-7) to the target (N,N'-propane-1,3-diylbis[3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionamide]; CAS 69851-61-2) includes the following: (1) Structural similarity, (2) Source and target are expected to hydrolyse in a similar fashion, (3) Source and target have similar predicted metabolism, (4) Source and target have similar physicochemical properties, (5) Source and target have similar calculated chemical descriptors, and (6) Source and target have similar predictions for the endpoints of concern. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.

 

Three male rabbits were exposed to the test substance dermally at 2000 mg/kg for 24 hours under occlusive conditions. No mortality, clinical signs, or cutaneous reactions were observed. The LD50 in rabbits was >2000 mg/kg.

Justification for classification or non-classification

Based on the oral and dermal LD50 in rats and rabbits of >10000 and >2000 mg/kg, respectively, no classification is required for acute oral or dermal endpoints according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.