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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 2013-05-22 to 2013-07-10

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

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:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 8 weeks old on the day of treatment
- Mean body weight at study initiation: the males had a mean body weight of 401 g (range: 391 g to 409 g) and the females had a mean body weight of 192 g (range: 182 g to 201 g)
- Fasting period before study: no
- Housing: the animals were housed by five from the same sex and group in polycarbonate cages with stainless steel lids
- Diet: SSNIFF R/M-H 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): 22 ± 2°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: 11 June 2013 to 28 June 2013.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of body surface, dorsal site
- Type of wrap if used: hydrophilic gauze pad + adhesive hypoallergenic aerated semi-occlusive dressing

REMOVAL OF TEST SUBSTANCE
- Removal of dressing: 24h post-exposure
- Washing: at 24h post-exposure, with a moistened cotton pad

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The quantity of test item applied to each animal was adjusted according to the body weight recorded on the day of dose application.
- Constant volume: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw.

No. of animals per sex per dose:

Ten Sprague-Dawley rats (five males and five nulliparous and non pregnant females).

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Clinical observations: frequently during the hours following treatment; then, at least once a day.
- Body weight: just before treatment on day 1; then on days 8 and 15.
- Necropsy of survivors performed: yes

Statistics:

None

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No unscheduled deaths occurred during the study.

Clinical signs:

No clinical signs were observed in any animals.

Body weight:

The mean body weight gain was unaffected by the test item treatment.

Gross pathology:

There were no macroscopic findings at necropsy.

Other findings:

On the application site, 4/5 females showed a very slight to well defined erythema on day 3 or from day 3 up to day 4 or 6, associated with dryness of the skin from day 3 or 5 up to day 6 or 7. In one of these four females, scabs were also observed from day 3 to day 5. Moreover, 3/5 males presented a very slight erythema on the application site on day 3 or days 3 to 4. These local reactions were considered to be related to the test substance.
No cutaneous reactions were noted in other animals.

Any other information on results incl. tables

Table 7.2.3/1: Mean body weight changes (g) in treated animals during the observation period compared to laboratory historical control data

 

Sex	Female		Male
Group	Laboratory Historical control data	1	Laboratory Historical control data	2
Dose-level (mg/kg bw)	0	2000	0	2000
Body weight (mean (± SD))
. Day 1	236 (± 8.9)	192 (± 7.2)	362 (± 12.0)	401 (± 6.8)
. Day 8	253 (± 12.0)	223 (± 9.9)	394 (± 15.3)	435 (± 11.7)
. Day 15	273 (± 16.3)	247 (± 9.5)	441 (± 21.5)	474 (± 16.7)
Body weight change (mean (± SD))
. Days 1-8	+17 (± 11.0)	+31 (± 7.9)	+32 (± 9.1)	+34 (± 7.9)
. Days 8-15	+20 (± 7.1)	+24 (± 6.5)	+47 (± 7.5)	+39 (± 5.1)
. Days 1-15	+37 (± 16.3)	+55 (± 6.7)	+79 (± 15.6)	+73 (± 12.0)

SD: standard deviations.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 of the test substance was higher than 2000 mg/kg bw in rats.
Therefore, 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 substance was tested for acute dermal toxicity according to OECD 402 guideline and in compliance with Good Laboratory Practices.

The test item was applied in its original form to the skin of five female then five male Sprague‑Dawley rats at the dose-level of 2000 mg/kg bw. The application site was covered by a semi‑occlusive dressing for 24 hours.

Each animal was observed at least once a day for mortality and clinical signs for 15 days. From day 2, any local reactions at the treatment site were also noted. Body weight was recorded the day before treatment, then on days 1, 8 and 15.

On completion of the observation period, the animals were sacrificed and then submitted to a macroscopic post-mortem examination.

No unscheduled deaths occurred during the study and no clinical signs were observed in any animals.

Local reactions such as erythema, dryness of the skin and scabs were transiently noted in 7 out 10 animals given 2000 mg/kg bw. These were considered to be treatment- related.

When compared to historical control data, the mean body weight gain was considered to be unaffected by the test item treatment in males and females. At necropsy, there were no macroscopic findings related to the test item administration.

The acute dermal LD50 was found greater than 2000 mg/kg bw.