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Administrative data

Description of key information

Oral (OECD 423): LD50 > 2000 mg/kg bw (limit test)

Dermal (OECD 402): LD50 > 2000 mg/kg bw (limit test)

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:
13 - 28 Mar 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
adopted in 2001
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Slovenska Narodna Akreditacna Sluzba, Bratislava, Slovenska Republika
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9 - 10 weeks
- Weight at study initiation: 172 - 195 g (step 1), 193 - 204 g (step 2)
- Fasting period before study: animals were fasted over-night prior to administration and after administration for further 3 - 4 h
- Housing: 3 animals per cage in plastic cages suspended on stainless steel racks on Lignocel S3/4 bedding (Lufa-ITL GmbH, Germany)
- Diet: laboratory food ssniff (Spezialdiäten GmbH, Germany) was offered at recommended doses each day approximately at the same time (analyses were performed)
- Water: tap water, ad libitum (analyses were performed)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.09 ± 0.21
- Humidity (%): 54.33 ± 2.34
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
olive oil
Details on oral exposure:
VEHICLE
- Justification for choice of vehicle: standard vehicle according to OECD TG 423

DOSAGE PREPARATION: The required amount of the test item (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration

Doses:
2000 mg/kg bw (step 1 and 2)
No. of animals per sex per dose:
3 females per step (2 steps)
Control animals:
no
Remarks:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually immediately after administration of the test item and 0.5, 1, 2 and 4 hours later. Each animal was inspected daily for the next 14 days. Observations included: changes in skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity, and behavioural pattern. Particular attention was given to potential neurologic endpoints such as tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Body weights were determined immediately prior to administration of the test item and weekly thereafter.
- Necropsy of survivors performed: yes
Sex:
female
Dose descriptor:
LD50 cut-off
Effect level:
>= 5 000 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred during the study period.
Clinical signs:
Animals displayed no signs of intoxication, change of health, nor any other adverse reaction.
Body weight:
Normal body weight gains were observed in all animals.
Gross pathology:
No macroscopic findings were observed in any animal.

Table 1: Absolute body weights and body weight gain

Step  Animal No. Starting dose (mg/kg bw) Body weight (g) Body weight gain (week 2 - Initial (g)
Initial Week 1 Week 2
1 1 2000 179 203 220 41
2 195 198 202 7
3 172 188 203 31
2 4 193 194 201 8
5 206 219 234 28
6 204 222 230 26
Interpretation of results:
other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute oral toxicity study a LD50 value > 2000 mg/kg bw in female rats was found.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

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:
14 - 30 May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
adopted in 2017
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
Slovenska Narodna Akreditacna Sluzba, Bratislava, Slovenska Republika
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Dobrá Voda, Slovak Republic
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 8-9 weeks
- Housing: 1-3 animals per cage in plastic cages suspended on stainless steel racks on Lignocel S3/4 bedding (Lufa-ITL GmbH, Germany)
- Diet: laboratory food ssniff (Spezialdiäten GmbH, Germany), ad libitum (analyses were performed)
- Water: tap water, ad libitum (analyses were performed)
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.6 ± 0.56
- Humidity (%): 54.34 ± 2.71
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10
- Type of wrap if used: semi-occlusive dressing with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing: with lukewarm water
- Time after start of exposure: 24 h



Duration of exposure:
24 h
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed individually immediately after the application of the test item and then 0.5, 1, 2, 4 and 6 hours later. Each animal was inspected daily for the next 14 days. Observations included changes in skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous systems, and somatomotor activity and behaviour pattern. Attention was directed to observations of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma. In addition, the treatment site was observed at 24, 48 and 72 hours after removal of test item using the Draize criteria.
- Body weights: Individual weights of animals were determined shortly before the test item was applied and weekly thereafter.
- Necropsy of survivors performed: yes
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the study
Clinical signs:
No clinical signs of intoxication, neither change of health nor skin reactions were noted.
Body weight:
The body weights of all animals were increasing during the study. No body weight losses were observed between the first and second week after administration.
Gross pathology:
At necropsy, no macroscopic changes were noted.

Table 1. Body weights

Sex

Dose

ID

Body Weight (g)

Body Weight Difference (g)

Initial

Week 1

Week 2

Week 1 - Initial

Week 2 - Initial

Week 2 - Week 1

 

 

2000 mg/kg bw

1

188

203

211

15

23

8

2

193

198

200

5

7

2

3

201

205

212

4

11

7

Interpretation of results:
other: CLP/ EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In this acute dermal toxicity limit study a LD50 value > 2000 mg/kg bw infemale rats was derived.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study, and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Oral

Acute oral toxicity was evaluated in a study performed according to OECD guideline 423 and in compliance with GLP (Hameln, 2018). Six female rats (3 per step) received an oral dose of 2000 mg/kg bw substance per gavage. No mortality and no signs of intoxication, change of health, nor any other adverse reaction was found in any animal during the 14 days of observation. The body weight of all animals increased during the study and no macroscopic findings were observed during necropsy. The oral LD50 was considered to be > 2000 mg/kg bw. Therefore, the test substance is not considered to have an acute toxicity potential via the oral route.

Dermal

Acute dermal toxicity was evaluated in a limit test performed according to OECD guideline 402 and in compliance with GLP (Hameln, 2018). Three female rats received a dermal dose of 2000 mg/kg bw test item held in place via a semi-occlusive dressing for 24 h. After 24 h the application site was washed with lukewarm water. No mortality, neither signs of intoxication, nor local signs of skin irritation were noted in any animal during the 14 days of observation. All animals gained body weight during the study and during necropsy no macroscopic changes were observed. The dermal LD50 was considered to be > 2000 mg/kg bw. Therefore, the test item is not considered to have an acute toxicity potential via the dermal route.

Justification for classification or non-classification

The available data on acute oral and dermal toxicity do not meet the classification criteria according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.