[No public or meaningful name is available]

Endpoint summary

Description of key information

acute oral toxicity rat (OECD TG 423): LD50 > 2000 mg/kg bw

acute dermal toxicity rat (OECD TG 402): LD50 > 2000 mg/kg bw

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:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: CD / Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approx. 8 weeks
- Weight at study initiation: 178-195 g
- Housing: 3 animals per cage
- Diet (e.g. ad libitum): yes
- Water (e.g. ad libitum): yes
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3 °C
- Humidity (%): 55 ± 10 °C
- Photoperiod (hrs dark / hrs light): 12h rhythm

IN-LIFE DATES: From: To: 25 May 2018 to 20 JUNE 2018

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The liquid test item was used as supplied. The administration volume was 1.89 mL/kg b.w. as the density was determined to be 1.06 g/mL.

No test item-formulation analysis had to be carried out as the dose level of 2000 mg/kg b.w. was used as supplied. As no animal died prematurely at this dose level, no test item-formulation had to be prepared.

Doses:

2000 mg/kg

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on prematurely deceased animals were made at least once daily to minimize loss of animals during the study. The time of death would have been recorded as precisely as possible. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
At the end of the experiments, all animals were sacrificed, dissected and inspected macroscopically. All gross pathological changes were recorded.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

no deaths

Clinical signs:

other: Treatment resulted in slightly to moderately reduced motility, slight to moderate ataxia, slightly reduced muscle tone and slight dyspnoea in 6 of 6 animals as well as pilo-erection in 5 of 6 animals and abdominal position in 2 animals between 60 minutes

Gross pathology:

no findings

Other findings:

none

Interpretation of results:

GHS criteria not met

Executive summary:

The acute oral LD50 in rats is determined with >2000 mg/kg bw based on the results of a limit dose study performed according to OECD TG 423. The test dose of 2000 mg/kg resulted in clinical signs as slightly to moderately reduced motility and ataxia, slight dyspnoea, pilo-erection and abdominal position between 60 minutes and 6 hours after administration. No clinical signs were observed from test day 2 until the end of the study. All animals gained the expected body weight and no gross pathological findings were recorded.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

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:

2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

2017

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: CD / Crl: CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: approximately 9 weeks for males
- Weight at study initiation: 209-220 g
- Housing: Before and after exposure period the animals were kept in groups of 3 animals per cage. Duriing the 24-hour exposure the animals were caged individually.
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
The intact dorsal skin of the animals was shaved free of hair with a shaver on the day before administration of the test item. The site was situated on the animal´s back between the fore and hind extremities and had an area of at least 5 cm x 6 cm (approx. 1/10 of body surface).

The test patch was occlusive. The test item was held in contact with the skin with 8 layers of gauze. The gauze was covered with a plastic sheet and secured with adhesive plaster strips5 on the application site for 24 hours.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw per 30.0 cm² (administration volume 1.89 mL/kg bw)

No. of animals per sex per dose:

one dose level with 2 females (plus 1 female for dose range finding)

Control animals:

no

Details on study design:

Dose range finding (1 female):
The dose level of 2000 mg/kg b.w. was chosen as starting dose as an oral toxicity study with a comparable product resulted in an LD50 above 2000 mg/kg b.w. as stated in the Safety Data Sheet.

Main study (2 females):
Based on the outcome in the range-finding study, the main study was conducted with 2 further animals at the dose level of 2000 mg/kg b.w. to confirm the classification outcome.
Following administration, observations were made and recorded systematically with individual records being maintained for each animal. Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days.
During the follow-up period of two weeks, changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory, autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Attention was also paid to possible tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
Observations on prematurely deceased animals were made at least once daily to minimize loss of animals during the study. The time of death would have been recorded as precisely as possible. Individual body weights were recorded before administration of the test item and thereafter in weekly intervals up to the end of the study. Changes in weight were calculated and recorded.
The application sites were observed daily and scored using the Draize criteria.
- Necropsy of survivors performed: yes

The classification category for the test item was determined in accordance with the flow chart for the testing procedure given in the OECD Guideline for the Testing of Chemicals No. 402, Annex 2.

Statistics:

No statistical analysis could be performed (the method used is not intended to allow a calculation of a precise LD50 value).

Preliminary study:

The dose range finding at 2000 mg test item/kg b.w. carried out in 1 female animal did not result in signs of toxicity or premature death.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occurred.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

No skin irritating effects and no pathological changes were observed at necropsy.

Interpretation of results:

GHS criteria not met

Executive summary:

An acute dermal toxicity study was performed according to OECD TG 402. For the purpose of a limit test 2000 mg/kg of the test item was applied occlusively for 24 hours to the skin of 1 female rat in the dose range finding study and additional 2 female rats in the main study. No mortalities, no clinical signs, no effects on weight development, no skin irritation and no gross pathological findings were observed during the 14-days observation period. The resulting dermal LD50 was thus determined with > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Additional information

The acute oral LD50 in rats is determined with > 2000 mg/kg bw based on the results of a limit dose study performed according to OECD TG 423. The test dose of 2000 mg/kg resulted in clinical signs as slightly to moderately reduced motility and ataxia, slight dyspnoea, pilo-erection and abdominal position between 60 minutes and 6 hours after administration. No clinical signs were observed from test day 2 until the end of the study. All animals gained the expected body weight and no gross pathological findings were recorded.

An acute dermal toxicity study was performed according to OECD TG 402 (2017). For the purpose of a limit test 2000 mg/kg of the test item was applied occlusively for 24 hours to the skin of 1 female rat in the dose range finding study and additional 2 female rats in the main study. No mortalities, no clinical signs, no effects on weight development, no skin irritation and no gross pathological findings were observed during the 14-days observation period. The resulting dermal LD50 was thus determined with > 2000 mg/kg bw.

Justification for classification or non-classification

Acute oral and acute dermal limit dose toxicity studies in rats, following OECD TG 423 and OECD TG 402 (2017), respectively, are available for the registered substance. Oral as well as dermal toxicity was determined with LD50 values of > 2000 mg/kg bw. Thus, no classification is warranted for acute toxicity.