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Diss Factsheets

Administrative data

Description of key information

There are no structural concerns for sensitisation, and cross-reading to data from structurally similar substance does not show sensitising properties.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Justification for type of information:
For details and justification of read-across please refer to the report attached in section 0.2 of IUCLID.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.15%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Erythema, edema and dryness and sloughing of the epidermis
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.15%
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Erythema, edema and dryness and sloughing of the epidermis
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
not specified
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Erythema, edema and dryness and sloughing of the epidermis
Remarks on result:
no indication of skin sensitisation
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
not specified
No. with + reactions:
1
Total no. in group:
10
Clinical observations:
Erythema, edema and dryness and sloughing of the epidermis
Remarks on result:
no indication of skin sensitisation
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
15%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
based on historical positive control data (study period: 25.01.1995 - 25.02.1995)
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
15%
No. with + reactions:
9
Total no. in group:
10
Remarks on result:
positive indication of skin sensitisation
Remarks:
based on historical positive control data (study period: 25.01.1995 - 25.02.1995)
Interpretation of results:
not sensitising
Conclusions:
The test substance is not sensitising to the skin of guinea-pigs under the conditions of the study. 0.15% of the test material for 6 hours seems to be the threshold for irritation in guinea pigs.
Executive summary:

A contact hypersensitivity study in the guinea pig was performed in compliance with Method B6, 92/69/EEC, in accordance with a modification of the method described in BUEHLER, E.V (1965) Arch. Dermatol., 91, 171. Twenty test and ten control animals were used.

In a preliminary study, the topical irritancy of a range of dilutions of the test substance in distilled water was investigated.

The study identified the concentration suitable for producing irritation suitable for the induction phase and a maximum non-irritant concentration for the challenge:

-For the induction phase; 1% v/v in distilled water. (0.3% a.s.)

-For the challenge phase; 0.5% v/v in distilled water. (0.15% a.s.)

Induction: Prior to each application, the skin on the left shoulder region was clipped free of hair. A 20 x 20 mm patch of surgical gauze (3 layers thick) was saturated with approximately 0.5 mL of the 1% v/v test substance.

The patch was placed on the skin and covered by impermeable plastic adhesive tape (50 mm width “Blenderm”). This was secured with elastic adhesive bandage (50 mm width “Elastoplast”) wound round the torso of the animal and fixed with “Sleek” impervious plastic adhesive tape. Contact was maintained for approximately 6 hours for each induction exposure. Reactions were noted 24 hours after dressing removal.

Induction took place on Days 1, 8, and 15 (a total of 3 inductions).

Control animals were treated similarly to test animals with the exception of test substance omission from the induction applications.

Challenge: Control and test animals were topically challenged two weeks after the final induction. An area of 50 x 50 mm on the right flank of the animal was clipped free of hair. A 20 x 20 mm gauzepatch (3 layers thick) was saturated with approximately 0.5 ml of the 0.5% v/v test substance. The patch was sealed to the skin under a 5cm strip of “Blenderm” covered by “Elastoplast” wound around the trunk and sealed with “Sleek”. After approximately 6 hours the dressings were removed.

Challenge sites were evaluated 24 and 48 hours after removal of the patches. Dermal reactions were scored on a numerical system for oedema and erythema. Evaluations were performed blind (i.e. the scorer had no knowledge of previous scores).

The animals were observed daily for clinical signs of toxicity.

Body weights were recorded on Day 1 (first day of topical application) and on the last day of observations for the challenge. Localised dermal reactions were observed in 3/10 control animals at the 24-hour observation and 1/10 control animals at the 48-hour observation, consisting of varying dermal responses of erythema, oedema and dryness and sloughing of the epidermis. 5/20 test animals at the 24-hour observation and 4/20 test animals at the 48-hour observation exhibited very slight erythema with or without very slight oedema and dryness and sloughing of the epidermis. Two other test animals exhibited dryness and sloughing of the epidermis only, at the 48-hour observation. It was concluded that none of the test animals showed a positive response.

This information is used in a read-across approach in the assessment of the target substance. For details and justification of read-across please refer to the read-across report attached to IUCLID section 0.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

There is no sensitization study available for Branched triamine C16-18. The molecular structure of the substance does not contain toxicophores indicating a concern for sensitization.

Additionally, a Buehler study was performed on a structurally similar branched triamine C12:

The study was performed in accordance with EU Method B.6 and under GLP, using 0.33% (recalculated for pure substance) aqueous solution for induction and 0.15% (recalculated for pure substance) aqueous solution for challenge, gave a negative outcome for sensitization (Huntingdon Life Sciences, 1996). Twenty guinea pigs were used in the test group and 10 in the control. The dose levels were chosen based on the results of a preliminary range-finding study. The higher concentration was the concentration that produced some irritation but did not give rise to adverse effects, while the lower was the maximum concentration not giving rise to irritating effects. Animals were induced epicutaneously under occlusive conditions, using a 6 hours exposure regime at Days 1, 8 and 15. Two weeks later, they were challenged epicutaneously once, using 6 hours exposure duration under occlusion, and skin reactions were scored 24 and 48 hours after the removal of the patches. None of the test animals displayed evidence of induced hypersensitivity.

This data based on read across from a structurally similar branched triamine C12 is also valid for branched triamine C16 -18. Branched triamine C16-18 only differs in the length of the alkyl chain, which is suspected to influence aspects related to bioavailability, but not aspects of chemical reactivity and route of metabolisation, aspects that determine specific mechanisms of toxicity relevant for sensitisation. For these reasons, many of the studies can best be performed on the substance with the shortest chain length within a group of structurally similar substances, as this is considered to represent the most sensitive species to show specific effects.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

There is no information on respiratory sensitisation. However, no concerns are expected.

As chemical respiratory sensitisers also elicit positive results in predictive tests for contact sensitisation, a negative outcome for dermal sensitisation is also predictive for non respiratory sensitisation of the substance. As indicated, the molecular structure of the polyamines does not contain toxicophores indicating a concern for sensitization, and also read across to data available on structurally same branched dipropylane triamines and primary amines in general do not indicate a concern. Consequently, respiratory sensitisation is not expected from polyamines.

Additionally, the likelihood for exposure via inhalation and thus becoming sensitised to polyamines, is very low, based on the high boiling point (> 300 °C) and very low vapour pressure (1.4 x 10-4 Pa at 25 °C for the branched triamine C12, with the shortest average alkyl chain length representing the highest vapour pressure for the group of branched polyamines)

Justification for classification or non-classification

Based on the available data, the substance does not need to be classified for skin sensitization in accordance with Directive 67/548/EEC and EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.