Reaction products of diphenylamine with nonene, branched

Endpoint summary

Description of key information

The substance was tested for its irritating potential to the skin and eye via a GLP compliant OECD 404 and a study similar/equivalent to OECD 405, respectively.

It can be concluded that the test substance is not irritating after skin or eye contact under the test conditions chosen.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Dec 2019 - Feb 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

July 28, 2015

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Landesanstalt für Umwelt Baden-Württemberg

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
-Test item No.: 12/0227-2
- Batch No.of test material: 0016046440
- Expiration date of the lot/batch: January 07, 2020
- Purity: 100 g / 100 g (UVCB substance)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature; avoid temperature < 10°C
- The stability of the test item under storage conditions over the test period was guaranteed by the sponsor
- Solubility and stability of the test substance in the solvent/vehicle: The test item was homogeneous by visual inspection

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Undiluted applicaton

OTHER SPECIFICS:
- Density [g/mL]: 0.960 (dertermined by testing facility)
- Physical state/ color: Liquid, viscous / yellowish to pink, clear
- pH-value: Approx. 5.5 (undiluted test item, determined by testing facility)

Species:

rabbit

Strain:

New Zealand White

Remarks:

Crl:KBL(NZW) – (SPF)

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Age at study initiation: Approx. 6 months
- Weight at study initiation: 4.03 kg – 4.44 kg
- Sex: Males
- Housing: Single housing in stainless steel wire mesh cages with grating with shallow cage body; floor area: 4225 cm². The animals were housed in fully air-conditioned rooms
- Diet (e.g. ad libitum): STANRAB (P) SQC; SDS Special Diets Services, 67122 Altrip, Germany, ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: At least 5 days before application

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20°C ± 3°C
- Humidity (%): 30 – 70%
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin sites of the same animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): Undiluted test substance

Duration of treatment / exposure:

Exposure for 4 hours

Observation period:

up to day 21

Number of animals:

3 animals

Details on study design:

TEST SITE
- Area of exposure: 2.5 cm x 2.5 cm
- Type of wrap if used: The test substance was covered with a test patch (Idealbinde, Pfälzische Verbandstoff-Fabrik, Kaiserslautern) and Fixomull® stretch (adhesive fleece), Beiersdorf AG

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The test substance was removed at the end of the exposure period with Lutrol® and Lutrol®/water (1 : 1).
- Time after start of exposure: 4h

OBSERVATION TIME POINTS
- Readings at 24, 48 and 72 h

SCORING SYSTEM:
According to OECD guideline 404

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24-72 h

Score:

1.1

Max. score:

4

Reversibility:

not fully reversible within: 21 days

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 24-72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema, respectively.
The cutaneous reactions were reversible in one animal within 24 hours, in a second animal within 14 days after removal of the patch.
In one animal, the cutaneous reactions were not reversible within 21 days. In this animal, very slight erythema (grade 1) and yellowish discoloration were seen on study day 21.

Other effects:

yellowish discoloration of the application area in some animals

Tab.1: Tabulation of irritant response, data for each individual animal at each observation time as well as calculation of the means

Readings	Animal No.	Erythema	Edema	Additional Findings
0h	1	1	0
	2	1	0
	3	1	0
1h	1	1	0
	2	2	0
	3	2	0
24h	1	0	0
	2	2	0
	3	2	0
48h	1	0	0	yellowish discoloration of the application area
	2	2	0	-
	3	1	0	-
72h	1	0	0	yellowish discoloration of the application area; SD
	2	2	0	yellowish discoloration of the application area
	3	1	0	yellowish discoloration of the application area
7d	1	-	-
	2	2	0	yellowish discoloration of the application area
	3	1	0	yellowish discoloration of the application area
14d	1	-	-	-
	2	0	0	yellowish discoloration of the application area; SD
	3	1	0	yellowish discoloration of the application area
21d	1	-	-	-
	2	-	-	-
	3	1	0	yellowish discoloration of the application area
Mean 24h – 72h	1	0.0	0.0
	2	2.0	0.0
	3	1.3	0.0
Mean	-	1.1	0.0

Interpretation of results:

GHS criteria not met

Conclusions:

Considering the described cutaneous reactions as well as the average score for irritation, the test substance does not show a skin irritating potential under the test conditions chosen.

Executive summary:

The potential of the test substance to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal, supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and at weekly intervals until day 21 at the latest.

The following test item-related clinical observations were recorded during the course of the study:

- Very slight to well-defined erythema (grade 1 to 2)

- Yellowish discoloration of the applications area

The cutaneous reactions were reversible in one animal within 24 hours and in a second animal within 14 days after removal of the patch. In one animal, cutaneous reactions were not reversible within 21 days. In this animal, very slight erythema (grade 1) and yellowish discoloration were seen on study day 21.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema, respectively.

Considering the described cutaneous reactions as well as the average score for irritation of the test item, it does not show a skin irritating potential under the test conditions chosen.

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:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Body weights not reported

GLP compliance:

yes

Specific details on test material used for the study:

Test material name: Naugalube 438L CN 5294300
Supplier: Uniroyal Inc.
Description: Brown viscous liquid
storage at ambient temperature and humidity

Species:

rabbit

Strain:

other: Albino, not further specified

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Nicholas Helf
- Age at study initiation: no data
- Weight at study initiation: no data
- Housing: 2 per cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled
- Humidity (%): controlled
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: 1 August 1983 To: 4 August 1983

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

0.1 ml

Duration of treatment / exposure:

single treatment

Observation period (in vivo):

3 ays

Number of animals or in vitro replicates:

6

Details on study design:

The test article was placed by syringe or syringe-type applicator into the conjunctival sac which was formed by gently pulling the lower eye1 i d away frorn the
eye. After instilllation, the lids were held together briefly to insure adequate distribution of the test article, One eye of each rabbit was dosed. The contralateral
eye served as a control. No washing step was included.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

3

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

None of the six treated animals showed any sign of ocular irritation.

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation/corrosion

The potential of the test substance to cause acute dermal irritation or corrosivity was assessed by a single topical application of an amount of 0.5 mL of the test item for 4 hours to the intact skin of three New Zealand White rabbits (stepwise procedure starting with one animal, supplementing two additional animals), using a patch of 2.5 cm x 2.5 cm, covered with semi-occlusive dressing. After removal of the patch the application area was washed off. The cutaneous reactions were assessed immediately after removal of the patch, approximately 1, 24, 48 and 72 hours after removal of the patch and at weekly intervals until day 21 at the latest.

The following test item-related clinical observations were recorded during the course of the study:

- Very slight to well-defined erythema (grade 1 to 2)

- Yellowish discoloration of the applications area

The cutaneous reactions were reversible in one animal within 24 hours and in a second animal within 14 days after removal of the patch. In one animal, cutaneous reactions were not reversible within 21 days. In this animal, very slight erythema (grade 1) and yellowish discoloration were seen on study day 21.

Mean scores over 24, 48 and 72 hours for each animal were 0.0, 2.0 and 1.3 for erythema and 0.0, 0.0 and 0.0 for edema, respectively.

Considering the described cutaneous reactions as well as the average score for irritation of the test item, it does not show a skin irritating potential under the test conditions chosen.

Eye irritation

The potential of the test substance to cause acute eye irritation was assessed in an in vivo eye irritation study (similar/equivalent to OECD 405) in rabbits. The test substance (0.1 mL) was placed by syringe or syringe-type applicator into the conjunctival sac and effects were observed for an obervation period of 3 days. None of the six treated animals showed any sign of ocular irritation.Thus, the test substance does not show an eye irritating potential under the test conditions chosen.

Justification for classification or non-classification

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. A GLP-compliant OECD 404 study is available for skin irritation. A GLP-compliant eye irritation study equivalent or similar to the OECD 405 guideline is available for eye irritation. In both studies, the scores for the test item treated tissues were below the thresholds for classification as an irritant. As a result, the substance is not considered to be classified for skin or eye irritation under Regulation (EC) No. 1272/2008, as amended for the fourteenth time in Regulation (EC) No. 2020/217.