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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 05 October 2012 to 31 October 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the OECD internationally recognised guideline and according to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
removal of the furtake place 27h before the test instead 24h +/- 2h
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
removal of the furtake place 27h before the test instead 24h +/- 2h
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Acacia mearnsi, ext., reaction products with ammonium chloride and formaldehyde
EC Number:
285-077-0
EC Name:
Acacia mearnsi, ext., reaction products with ammonium chloride and formaldehyde
Cas Number:
85029-52-3
Molecular formula:
Not necessary (UVCB substance)
IUPAC Name:
Acacia mearnsi, ext., reaction products with ammonium chloride and formaldehyde
Test material form:
other: Liquid
Details on test material:
- Name of test material (as cited in study report): Acacia mearnsi, ext., reaction products with amonium chloride and formaldehyde
- Substance type: UVCB
- Physical state: liquid
- Density: 1.1-1.2
- Analytical purity: 100%
- Storage condition of test material: room temperature, protected from light
- Stabilty in container and water: stable

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Strain: Wistar rats Crl: WI(Han) (full barrier)
- Age at study initiation:males, 8-10weeks and female, 11-12 weeks
- Weight at study initiation: males, 245-254 g and females, 216-240 g
- Housing: the animal were kept individually in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 190612)
- Diet (e.g. ad libitum): free access to Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): free access to tap water, sulphur acidfied to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3°C
- Humidity (%): 55 +/- 10%
- Air changes (per hr): 10x/hour
- Photoperiod (hrs dark / hrs light): 12h/12h

Administration / exposure

Type of coverage:
other: The dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal
- % coverage: approximately 10%
- Type of wrap if used: the dressing consisted of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): test item was removed using aqua ad injectionem (Allem Pharma, lot no. 120203).
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): the test item was applied at a single dose of 2000 mg/kg body weight to each animal.
Duration of exposure:
- 24 hours
Doses:
- The test item was applied at a single dose of 2000 mg/kg body weight to each animal.
No. of animals per sex per dose:
- 5 males and 5 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of weighing: The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Frequency of observations: A careful clinical examination was made several times on the day of dosing (once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: cageside observations included changes in the skin and fur, eyes and mucous menbranes. Also respiratory, circulatory, autonomic amd central nervous systems and somatomotor activity and behaviour pattern were examinated. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, sleep and coma.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- No mortality
Clinical signs:
- No signs of toxicity but signs of dermal irritation: no erythema or oedema was observed. Eschar was observed in 1 of 5 male animals. Scratches were observed in 4 or 5 male and all female animals (see table 1 and table 2). All signs of irritation were reversible within the observation period.
Body weight:
- A slight weight loss was recorede for 4 out of 5 female animals during the first week, but all of the female animals showed weight gain during the second week. The effects on weight development might be secondary to the dressing, and toxicological relevance of this finding cannot clearly be concluded. The male animals showed weight gain during the first and second week of the observation.
Gross pathology:
- No specific findings for all animals.

Any other information on results incl. tables

Table 1: Skin Irritation, individual data for males

Day after startof application Animal No. 21 Animal No. 22  Animal No. 23 Animal No. 24 Animal No. 25
E/O Comments E/0 Comments E/O Comments  E/O  Comments  E/O  Comments 
day 2 0/0 nsf 0/0  nsf 0/0  nsf 0/0  nsf 0/0  nsf
day 3  0/0 s* 0/0  * 0/0  s* 0/0  s* 0/0  s*
day 4  0/0 s* 0/0  * 0/0  s* 0/0  s* 0/0  s*
day 5  0/0 s* 0/0  * 0/0  s* 0/0  s* 0/0  s*
day 6  0/0 s* 0/0  * 0/0  s* 0/0  s* 0/0  s*
day 7  0/0 s* 0/0  * 0/0  s* 0/0  s* 0/0  s*
day 8  0/0 s* 0/0  * 0/0  * 0/0  s* 0/0  *
day 9  0/0 s* 0/0  * 0/0  * 0/0  s* 0/0  *
day 10  0/0 s* 0/0  * 0/0  * 0/0  s* 0/0  *
day 11  0/0 s* 0/0  * 0/0  * 0/0  es* 0/0  *
day 12  0/0 s* 0/0 * 0/0  * 0/0  es* 0/0  *
day 13  0/0 * 0/0  * 0/0  * 0/0  * 0/0  *
day 14 0/0 * 0/0  * 0/0  * 0/0  * 0/0  *
day 15 0/0 * 0/0  * 0/0  * 0/0  * 0/0  *

E = erythema; O = oedema; 0,1,2,3,4 = scoring system laid down in OECD guideline 404; es = eschar; s = scratches; * = residual test item (yellow); nsf = no specific findings

Table 2: Skin Irritation, individual data for females

Day after startof application Animal No. 26 Animal No. 27 Animal No. 28 Animal No. 29 Animal No. 30
E/O Comments E/0 Comments E/O Comments  E/O  Comments  E/O  Comments 
day 2 0/0 nsf 0/0  nsf 0/0  nsf  0/0  nsf  0/0  nsf 
day 3  0/0 s* 0/0  s* 0/0  s* 0/0  s* 0/0  s*
day 4  0/0 s* 0/0  s* 0/0  s* 0/0  s* 0/0  s*
day 5  0/0 s* 0/0  s* 0/0  s* 0/0  s* 0/0  s*
day 6  0/0 s* 0/0  s* 0/0  s* 0/0  s* 0/0  s*
day 7  0/0 s* 0/0  s* 0/0  s* 0/0  s* 0/0  s*
day 8  0/0 s* 0/0  * 0/0  s* 0/0  s* 0/0  *
day 9  0/0 s* 0/0  * 0/0  s* 0/0  s* 0/0  *
day 10  0/0 s* 0/0  * 0/0  * 0/0  s* 0/0  *
day 11  0/0 s* 0/0  * 0/0  * 0/0  s* 0/0  *
day 12  0/0 s* 0/0 * 0/0  * 0/0  s* 0/0  *
day 13  0/0 s* 0/0  * 0/0  * 0/0  * 0/0  *
day 14 0/0 s* 0/0  * 0/0  * 0/0  * 0/0  *
day 15 0/0 * 0/0  * 0/0  * 0/0  * 0/0  *

E = erythema; O = oedema; 0,1,2,3,4 = scoring system laid down in OECD guideline 404; es = eschar; s = scratches; * = residual test item (yellow); nsf = no specific findings

Table 3: Absolute body weights in g and body weight gain in %

Dose: 2000 mg/kg body weight
Animal No. / Sex Day 1 (g) Day 8 (g) Day 15 (g) Day 1 -15 (%)
21 / male 245 266 292 19
22 / male 254 272 300 18
23 / male 254 288 321 26
24 / male 248 277 314 27
25 / male 251 285 316 26
26 / female 216 216 221 2
27 / female 227 218 226 0
28 / female 235 220 232 -1
29 / female 227 223 232 2
30 / female 240 233 239 0

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
According to Annex I of Regulation (EC) 1272/2008 the test item Acacia mearnsi extract is unclassified for acute dermal toxicity in the test conditions.
Executive summary:

Under the conditions of the present study, single dermal application of the test item Acacia mearnsi extract to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity but signs of dermal irritation. However, all signs of irritation were reversible within the observation period.

The dermal LD50 was determinated to be > 2000 mg Acacia mearnsi extract/kg body weight.

According to Annex I of Regulation (EC) 1272/2008 the test item Acacia mearnsi extract is unclassified for acute dermal toxicity and skin irritation in the test conditions.