Reaction products of 12-hydroxyoctadecanoic acid with ethane-1,2-diamine and hexane-1,6-diamine and 1,3-phenylenedimethanamine

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2012-11-02 to 2012-12-07

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

Reaction products of 12-hydroxyoctadecanoic acid with ethane-1,2-diamine and hexane-1,6-diamine and 1,3-phenylenedimethanamine

EC Number:

700-825-2

Molecular formula:

Not applicable (UVCB substance).

IUPAC Name:

Reaction products of 12-hydroxyoctadecanoic acid with ethane-1,2-diamine and hexane-1,6-diamine and 1,3-phenylenedimethanamine

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: CEGAV, Argenvilliers, France
- Age/weight at study initiation: at the beginning of the study, the animals were 2 to 4 months old and had a mean body weight of 3850 g (range: 3695 g to 3975 g)
- Fasting period before study: no
- Housing: the animals were individually housed in noryl cages
- Diet: 110 pelleted diet (free access)
- Water: tap water filtered with a 0.22 µm filter (free access)
- Acclimation period: at least 5 days before the beginning of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 50 ± 20%
- Air changes (per hr): approximately 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h.

IN-LIFE DATES: 27 November 2012 to 07 December 2012.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

other: clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: each animal served as its own control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 g/flank.

Duration of treatment / exposure:

3 min, 1 h, 4 h.

Observation period:

1, 24, 48 and 72 h after removal of the dressing and if relevant, daily until reversibility of reactions.

Number of animals:

3 males.

Details on study design:

TEST SITE
- Area of exposure: Right and left anterior and/or posterior flanks of the animals
- % coverage: 6 cm2
- Type of wrap if used: gauze pad held in place by a non-irritation semi-occlusive dressing and a restraining bandage.

REMOVAL OF TEST SUBSTANCE
- Washing:using a moistened cotton pad
- Time after start of exposure: at removal of each dressing (see Duration of exposure)

SCORING SYSTEM: according to OECD guideline 404

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Remarks:

: 4-hour exposure

Basis:

animal #1

Time point:

other: 24, 48, 72 h (mean)

Score:

0.7

Max. score:

4

Reversibility:

fully reversible

Results 2

Irritation parameter:

erythema score

Remarks:

: 4-hour exposure

Basis:

animal #2

Time point:

other: 24, 48, 72 h

Score:

0

Max. score:

4

Results 3

Irritation parameter:

erythema score

Remarks:

: 4-hour exposure

Basis:

animal #3

Time point:

other: 24, 48, 72 h (mean)

Score:

0

Max. score:

4

Results 4

Irritation parameter:

edema score

Remarks:

: 4-hour exposure

Basis:

animal #1

Time point:

other: 24, 48, 72 h (mean)

Score:

0

Max. score:

4

Results 5

Irritation parameter:

edema score

Remarks:

: 4-hour exposure

Basis:

animal #2

Time point:

other: 24, 48, 72 h (mean)

Score:

0

Max. score:

4

Results 6

Irritation parameter:

edema score

Remarks:

: 4-hour exposure

Basis:

animal #3

Time point:

other: 24, 48, 72 h (mean)

Score:

0

Max. score:

4

Irritant / corrosive response data:

After a 3-minute and a 1-hour exposures, a very slight erythema (grade 1) was observed from day 1 to day 4 in the treated animal .
After a 4-hour exposure, a well defined erythema (grade 2) was noted in one animal and a slight erythema (grade 1) was noted in the two others one hour after patch removal. At the 24-hour reading, a slight erythema was still present in one animal but cleared at the 72-hour reading.

Any other information on results incl. tables

Table 7.3.1/1 Cutaneous reactions after a 4 -hour exposure

Rabbit number	Dermal irritation	SCORES				Mean irritation score (1)
		1h	24h	48h	72h
		D1	D2	D3	D4
A30281	Erythema	2	1	1	0	0.7
	Edema	0	0	0	0	0.0
	Other	*	*	*	*
A30282	Erythema	1	0	0	0	0.0
	Edema	0	0	0	0	0.0
	Other	*	*	*	*
A30283	Erythema	1	0	0	0	0.0
	Edema	0	0	0	0	0.0
	Other	*	*	*	*

(1)    mean of scores on days 2,3 and 4

h = hour

D= day

* = none

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The substance is not classified according to Regulation (EC) No. 1272/2008 and its subsequent amendments on classification, labeling and packaging (CLP) of substances and mixtures.

Executive summary:

The potential of the test item to induce skin irritation was assessed in 3 rabbits according to OECD Guideline 404 in compliance with Good Laboratory Practices.

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single New Zealand White rabbit. After the 4-hour application, since the mean value from grading at 24, 48 and 72 hours after patch removal was < 2.3 for erythema or for edema, the test item was applied on the skin of two other animals for 4 hours.

A quantity of 0.5 g/flank was applied to a skin area of approximately 6 cm²under a semi-occlusive dressing for 4 hours. Skin reactions were observed 1, 24, 48, 72 hours after removal of the dressing. The mean values of the scores for erythema and oedema were calculated for each animal. Each animal was observed once a day for mortality and clinical signs. Body weight was recorded at the beginning and the end of the observation period. On completion of the observation period, the animals were used subsequently for the evaluation of the ocular irritation potential of the same test item.

No unscheduled deaths occurred during the study and no clinical signs indicative of systemic toxicity were noted in any animals.The body weight of the animals was unaffected by the test item treatment.

After a 4-hour exposure, a well defined erythema (grade 2) was noted in one animal and a slight erythema (grade 1) was noted in the two others one hour after patch removal. At the 24-hour reading, a slight erythema was still present in one animal but cleared at the 72-hour reading.

 The mean scores calculated for each animal over 24, 48 and 72 hours were 0.7, 0.0, 0.0 for erythema and 0.0, 0.0; 0.0 for oedema.

 It was concluded that the test item was slightly irritant when applied topically to rabbits.