Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine

Endpoint summary

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Reference

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 30 August to 11 September 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in accordance with validated testing guidelines and under GLP conditions.

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Species:

mouse

Strain:

CBA

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: Supplied by Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: Eight to twelve weeks old.
- Weight at study initiation: Range of 15 to 23 g.
- Housing: The animals were individually housed in suspended solid-floor polypropylene cages furnished with softwood woodflasks.
- Diet (e.g. ad libitum): Free access to mains food.
- Water (e.g. ad libitum): Free access to mains tap water.
- Acclimation period: At least five days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): Approximately 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06.00 to 18.00) and 12 hours darkness.

IN-LIFE DATES: From 30 August to 11 September 2012

Vehicle:

other: Butanone

Concentration:

50%, 25% or 10%

No. of animals per dose:

Four mice

Details on study design:

RANGE FINDING TESTS:
- Irritation: No signs of systemic toxicity, visual local skin irritation or irritation indicated by an equal to or greater than 25% increase in mean ear thickness were noted.

MAIN STUDY
ANIMAL ASSIGNMENT AND TREATMENT
- Criteria used to consider a positive response: Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine will be regarded as a sensitiser if at least one concentration of bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine results in a threefold or greater increase in 3HTdR incorporation compared to control values.

TREATMENT PREPARATION AND ADMINISTRATION:
Test item administration:
Groups of four mice were treated with bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine at concentrations of 50%, 25% or 10% w/w in butanone. The mice were treated by daily application of 25 μL of the appropriate concentration of bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine to the dorsal surface of each ear for three consecutive days (Days 1,2,3). Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine formulation was administered using an automatic micropipette and spread over the dorsal surface of the ear using the tip of the pipette.
A further group of four mice received the vehicle alone in the same manner.

3H-methyl thymidine administration:
Fives days following the first topical application of bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine or vehicle (Day 6) all mice were injected via the tail vein with 250 μL of phosphate buffered saline containing 3H-methyl thymidine giving a total of 20 μCi to each mouse.

Termination: Five hours following the administration of 3HTdR all mice were killed by carbon dioxide asphyxiation. The draining auricular lymph nodes from the four mice were excised and pooled for each experimental group. For each group 1 mL of PBS was added to the pooled lymph nodes.

Positive control substance(s):

not specified

Statistics:

None stated

Positive control results:

No information provided

Parameter:

SI

Remarks on result:

other: The Stimulation Index expressed as the mean radioactive incorporation for each treatment group divided by the mean radioactive incorporation of the vehicle control group are as follows: 1.68, 1.90 and 2.14 for 10%, 25% and 50% groups respectively.

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: The Disintegrations per minute are 8521.79, 14348.29, 16178.07 and 18200.30 for vehicle, 10%, 25% and 50% groups respectively.

Clinical Observations and Mortality Data:

There were no deaths. No signs of systemic toxicity were noted in the test or control animals during the test. Off white residual bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine was occasionally noted in test animals treated at a concentration of 50% w/w in butanone.

Bodyweight:

Bodyweight changes of the test animals between Day 1 and Day 6 were comparable to those observed in the corresponding control group animals over the same period.

Interpretation of results:

not sensitising

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine was considered to be a non-sensitiser under the conditions of the test.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In a study conducted according to OECD Guideline 429, conducted under GLP, female mice were exposed to bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine (Harlan Laboratories Ltd., 2012). In this study, bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine is not regarded as a skin sensitizer.

Migrated from Short description of key information:
bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amine is not regarded as a skin sensitizer (Harlan Laboratories, 2012).

Justification for selection of skin sensitisation endpoint:
The study was conducted according to OECD Guideline 429, under GLP conditions at a reputable European Union laboratory.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Skin Sensitisation:

In an animal study using bis(4-(1,1,3,3-tetramethylbutyl)phenyl)amide 0/4 animals displayed sensitisation.

Therefore, in accordance with Regulation No. 1272/2008 (amended in Regulation No. 286/2011) Table 3.4.2, bis(4 -(1,1,3,3 -tetramethylbutyl)phenyl)amide (CAS number 15721 -78 -5) is not classified as a skin sensitiser.

The test substance does not have to be classified and has no obligatory labelling requirement for sensitization by skin contact according to Regulation (EC) No 1272/2008 on classification, labelling and packaging of substances and mixtures.