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Administrative data

Description of key information

Oral: In the two available studies (and reliable study), the LD50 was determined to be > 2000 mg/kg bw.
Dermal: In the only available (and reliable study), the LD50 was determined to be > 2000 mg/kg bw.
Therefore, the test substance has no acute toxicity regarding oral and dermal routes in the test conditions and should not be classified according to 1272/2008/EC regulation.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 14 july 2006 to 08 August 2006
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.
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
not specified
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: between 8 and 12 weeks
- Weight at study initiation: between 171 and 229g
- Fasting period before study: 12 hours
- Housing: polypropylene boxes covered by metal grid and lined with wooden shavings, with a maximum number of 5 animals per box
- Diet (e.g. ad libitum): commercial feed ad libitum
- Water (e.g. ad libitum): filtered water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):
- Humidity (%):
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12h/12h
Route of administration:
oral: unspecified
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
- 1000 mg/mL, dose of 2000 mg/kg
Doses:
- Pre-test : 2000 mg/kg of live weight
- Final test : 2000 mg/kg of live weight
No. of animals per sex per dose:
- Pre-test : one animal (female) per doses
- Final test : 5 animals (female) per doses
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Frequency of weighing: at the beginning and at the end of the study
- Necropsy of survivors performed: yes (heart, lung, liver, stomach, intestines, kidneys, adrenal glands and spleen)
- Other examinations performed: clinical signs (skin, hair, eyes, mucosae, circulatory, respiratory, nervous systems, somatomotor) and behavioral activity
Preliminary study:
- Pre-test, one female rat oraly exposed at the dose of 2000 mg/kg of live weight: no death, the animal did not show clinical signs of toxicity
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Number of deaths: 0
Clinical signs:
- The animals did not show clinical signs of toxicity
Other findings:
- Other observations: respiratory system, cadiovasculatory system, digestive system, genitourinary system: not noteworthy up to the dose of 2000 mg/kg of live weight
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
- By oral route in the condition of the test, the substance is not toxic. According to the criteria given in Annex I of Regulation EC/1272/2008, the substance Acacia mearnsi extract should not be classified as hazadous for acute oral toxicity.
Executive summary:

The Acute Oral Toxicity Test-Fixed Dose for rats was conducted to study the potential toxic effects of ACQUAPOL C1. The product was used in pure form (liquid) and administrated orally to rats that were 8 - 12 weeks old, at the dose of 2000 mg/kg of live weight in the pre-test, and at the dose of 2000 mg/kg of live weight for the final test. The animals were observed for time to death, behavioral changes, clinical signs and macroscopic anatomopathological findings. The final test was conducted with a dose of 2000 mg/kg of live weight, in which the animals do not present clinical signs of toxicity, which allows the product ACQUAPOL C1 to be classified in toxicological class V (Non-toxic) according to the classification table for acute toxicological risk according to GHS-OECD by oral route. Moreover, according to the criteria given in Annex I of Regulation EC/1272/2008, the substance Acacia mearnsi extract should not be classified as hazadous for acute oral toxicity in the testing conditions (LD50 > 2000 mg/kg of live weight).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The supporting study is described in a brief summary and was not performeed according an official guideline. However, the most important informations are given, so that the study can be judged as scientifically acceptable.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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.
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
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
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.
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.

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
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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Test was performed according to the GLP and international guideline

Additional information

Oral

In the key study and scored as reliability 1 according to Klimisch an acute oral toxicity study conducted according to the OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method), groups of fasted, 8 -12 week old Wistar rats (5 females/dose for final test) were given a single oral dose of Acacia mearnsi extract in pure form (liquid form) at dose of 2000 mg/kg bw (limit test) and observed for 14 days.

In the supporting study, scored as reliability 2 according to Klimisch, an acute oral toxicity study (1998), groups of male Balb-C mouse (5/dose) were given a single oral dose of Acacia mearnsi extract (liquid form) at doses of 660, 1320, 2630, 5270 and 10530 mg/kg bw (final test concentrations) and observed for 7 days.
Both studies concluded:

Oral LD50 Combined (rat and mouse) > 2000 mg/kg bw

Inhalation

In accordance with the column 2 adaptation of column 1, REACH Annex VIII, the acute dermal toxicity study (required in section 8.5.2) is not considered scientifically justified as the oral and dermal exposure routes are the most appropriate to assess the acute toxicity hazard presented by the substance based on its physico-chemical characteristics and use pattern.

Dermal

In the only available study, conducted in accordance with the standardised guideline OECD 402 and thus scored as reliability 1 according to Klimisch, male and female rats (5 per sex) were exposed (approximately 10% of the total body surface, single dose) for 24 hours to a Acacia mearnsi extract (liquid form) concentration of 2000 mg/kg bw. All animals were observed for 14 days after dosing. At the end of the observation period all animals were sacrified and subject to gross necroscopy.

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.


Justification for selection of acute toxicity – oral endpoint
Test was performed according to the GLP accreditation and international guideline.

Justification for selection of acute toxicity – inhalation endpoint
A data waiver has been submitted to address this endpoint.

Justification for selection of acute toxicity – dermal endpoint
Only one study is available, the test was performed according to the GLP and international guideline.

Justification for classification or non-classification

Oral

In accordance with the criteria for classification as defined in the annex I of the Regulation 1272/2008/EC, the test material does not meet the criteria for classification for acute oral toxicity.

Dermal

In accordance with the criteria for classification as defined in the annex I of the Regulation 1272/2008/EC, the test material does not meet the criteria for classification for acute dermal toxicity.

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