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

Endpoint summary

Description of key information

Skin: Rabbit. Not irritating. Acute dermal study at limit dose with read-across substance. Reliability = 2

Eye: Rabbit. Not irritating. Scientifically Valid Study with read-across substance. Reliability = 2

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

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:

no guideline followed

Principles of method if other than guideline:

The test substance was tested for irritation in rabbit eye using the technique, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics of the US Association of Food and Drug Officials (AFDO).

GLP compliance:

no

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Obtained from suppliers in Switzerland
- Weight at study initiation: 2.2 to 2.7 kg
- Housing: Housed separately in wire cages (overall dimension 55 x 48 x 44 cm)
- Diet: NAFAG No. 84, ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 2
- Humidity (%): 55-60
- Photoperiod (hrs dark / hrs light): 12

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye was left untreated and served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 g

Duration of treatment / exposure:

Single instillation

Observation period (in vivo):

24 h, 2, 3, and 4 days

Number of animals or in vitro replicates:

6

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: Not washed

SCORING SYSTEM: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics of the AFDO

TOOL USED TO ASSESS SCORE: Slip lamp

- After application, the eyelids were held open for a few seconds

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

Not irritating

Executive summary:

The test substance was tested for irritation in rabbit eye using the technique, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics of the US Association of Food and Drug Officials (AFDO). The test substance was tested on 6 rabbits of the New Zealand strain. 0.1 g of the test substance was introduced into the conjunctival sac of the left eye with a spatula. After application, the eyelids were held open for a few seconds. The right eye was left untreated and served as a control. The reactions were appraised with a slip lamp after 24 hours and after 2, 3, and 4 days. Under the present experimental conditions, no irritant effects were seen when the test substance was introduced into the rabbit eye.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No skin or eye irritation studies with the test substance are available. Results from an acute dermal toxicity study and an eye irritation 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.

An acute dermal toxicity study with the read-across test substance was performed. Three male rabbits were exposed dermally at 2000 mg/kg for 24 hours under occlusive conditions. No cutaneous reactions were observed over the 8-day observation period.

An eye irritation study was performed on the read-across test substance. 0.1 g was introduced into the conjunctival sac of the left eye of 6 rabbits. No irritation was observed in any rabbit.

Justification for classification or non-classification

Based on effects observed in the acute dermal and eye irritation studies with the read-across substance, no classification is required for skin or eye irritation according to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.