[No public or meaningful name is available]

Endpoint summary

Description of key information

Acute Oral Toxicity

Under the conditions of the study, the acute oral LD50 of the test material in the female Wistar strain rat is greater than 2000 mg/kg body weight.

Acute Dermal Toxicity

Under the conditions of the study, the LD50 of the test material is greater than 2000 mg/kg body weight.

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 November 2017 to 28 November 2017

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)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 160-195 g
- Fasting period before study: Food but not water was withheld over-night prior to dosing and for 3 to 4 hours after dosing.
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 3 animals per cage in a room equipped with central air conditioning.
- Diet: The laboratory food was offered at recommended doses each day approximately at the same time.
- Water: Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 23.26 ± 0.16 °C
- Humidity: 53.35 ± 1.86 %
- Photoperiod: 12-hour light /12-hour dark cycle

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Olive oil is a standard vehicle according to OECD TG 423
- Lot/batch no.: L63417

MAXIMUM DOSE VOLUME APPLIED:
- The starting dose could be selected from the fixed dose levels of 5, 50, 300, and 2000 mg/kg body weight. A limit dose of 2000 mg/kg body weight was used as a starting dose. One group of 3 females was dosed. Test material-related mortality was not observed during 24 hours and therefore, in a second step, another 3 females were treated at the same dose.
- The required amount of the test material (according to the body weight and dose) was mixed with vehicle (olive oil) shortly before administration.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Animals were observed individually immediately after administration of the test material 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.
- Individual weights of animals were measured immediately prior to administration of the test material and weekly thereafter. Weight differences after first and second weeks after administration were calculated and recorded.
- Necropsy of survivors performed: Yes, all test animals were subjected to gross necropsy and the results were recorded for each animal.

Statistics:

No statistical analysis was done in conjunction with this study.

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:

other: - Piloerection was observed in animals No 3, 4 and No 5. The symptom started to appear 4 hours post-treatment and it persisted next two days. It reappeared from 10th day and it lasted until the end of the study. - Dyspnoea was observed from the first pos

Gross pathology:

All animals were necropsied. Increased amount of gas in gastrointestinal tract, microsplenia and atrophy of thymus were registered in animals No. 3, 4 and 5.

Table 1: Body Weight

ID	Body Weight (g)			Body Weight Difference (g)
	Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 – Week 1
1	190	195	200	5	10	5
2	185	200	210	15	25	10
3	195	210	160	15	-35	-50
4	160	165	115	5	-45	-50
5	175	180	140	5	-35	-40
6	175	200	200	25	25	0

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of the study, the acute oral LD50 of the test material in the female Wistar strain rat is greater than 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity of the test material was investigated in accordance with the standardised guideline OECD 423, under GLP conditions.

The test material was administered as a single oral dose to female Wistar rats, the Acute Toxic Class (ATC) method was used. A limit dose of 2000 mg/kg body weight was used as a starting dose.

The test material administered to 6 females at a limit dose did not cause death. Piloerection and dyspnoea were observed during the observation period. A decrease of body weights in 3/6 animals and stagnation of body weight in one animal were observed between the first and second week after administration of the test item. During necropsy, increased amount of gas in gastrointestinal tract, microsplenia and atrophy of thymus were registered.

Under the conditions of the study, the acute oral LD50 of the test material in the female Wistar strain rat is greater than 2000 mg/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

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:

22 November 2017 to11 December 2017

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-230 g
- Housing: The animals were housed in plastic cages suspended on stainless steel racks, up to 2-3 animals per cage in a room equipped with central air conditioning.
- Diet: The laboratory food was offered at recommended doses each day approximately at the same time.
- Water: Ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 23.28 ± 0.18 °C
- Humidity: 53.36 ± 1.9 %
- Photoperiod: 12-hour light /12-hour dark cycle

Type of coverage:

semiocclusive

Vehicle:

olive oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 24 hours before the test, fur was removed from the dorsal area of the trunk of the test animals by clipping and shaving.
- % coverage: approximately 10 % of the total body surface area
- Type of wrap if used: Test material was held in contact with the skin by using semi-occlusive dressing with non-irritating tape throughout the 24-hours exposure period.

REMOVAL OF TEST SUBSTANCE
- At the end of the exposure period (24 hours), any residuals of the test material were removed by using lukewarm water without altering the existing response or integrity of the epidermis.

TEST MATERIAL
- A limit dose of 2000 mg/kg body weight was used as a starting dose. One female was dosed. Test material-related mortality was not observed during 48-hours exposure period. The sighting study was finished; the main test was started with dose of 2000 mg/kg body weight. The additional 2 females were dosed in the Main Study with the dose of 2000 mg/kg body weight.
- Preparation: The required amount of the test material (according to the body weight and dose) was mixed with the vehicle (olive oil) shortly before application according to the actual body weight.

VEHICLE
- Lot/batch no.: L63417
- Olive oil is a standard vehicle according to OECD TG 402

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Animals were observed individually immediately after the application of the test material 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 material using the Draize criteria.
- Individual weights of animals were determined shortly before the test material was applied and weekly thereafter. Weight differences after first and second week after application were calculated and recorded.
- Necropsy of survivors performed: Yes, all test animals were subjected to gross necropsy. Full, detailed gross necropsy included careful examination of external surface of the body, all orifices, and cranial, thoracic and abdominal cavities and their contents. All gross pathological changes were recorded for each animal.

Preliminary study:

One female was dosed. Test material-related mortality was not observed during 48 hours.

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:

other: Animals lived through observation period without signs of intoxication. Neither change of health nor negative skin reactions were registered.

Gross pathology:

All animals were necropsied. During necropsy, no macroscopic changes were noticed.

Table 1: Body Weight

ID	Body Weight (g)			Body Weight Difference (g)
	Initial	Week 1	Week 2	Week 1 - Initial	Week 2 - Initial	Week 2 – Week 1
1	200	210	215	10	15	5
2	230	230	230	0	0	0
3	225	230	230	5	5	0

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of this study, the LD50 of the test material is greater than 2000 mg/kg bodyweight.

Executive summary:

The acute dermal toxicity of the test material was determined in accordance with the standardised guideline OECD 402, under GLP conditions.

The test material was applied as a single dermal dose to Wistar rats. A limit dose of 2000 mg/kg body weight was used as the starting dose. One female was dosed. Test material-related mortality was not observed during 48 hours. A total of three female rats were dosed with a limit dose of 2000 mg/kg body weight.

The test material applied to 3 females at a limit dose of 2000 mg/kg body weight did not cause death. The body weight of 2/3 females increased during the study, stagnation of body weight in one female was noticed. No signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours or 14-day observation period. No dermal changes were observed. During necropsy no macroscopic findings were noticed.

Under the conditions of this study, the LD50 of the test material is greater than 2000 mg/kg bodyweight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Additional information

Acute Oral Toxicity

The acute oral toxicity of the test material was investigated in accordance with the standardised guideline OECD 423, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The test material was administered as a single oral dose to female Wistar rats, the Acute Toxic Class (ATC) method was used. A limit dose of 2000 mg/kg body weight was used as a starting dose.

The test material administered to 6 females at a limit dose did not cause death. Piloerection and dyspnoea were observed during the observation period. A decrease of body weights in 3/6 animals and stagnation of body weight in one animal were observed between the first and second week after administration of the test item. During necropsy, increased amount of gas in gastrointestinal tract, microsplenia and atrophy of thymus were registered.

Under the conditions of the study, the acute oral LD50 of the test material in the female Wistar strain rat is greater than 2000 mg/kg body weight.

Acute Dermal Toxicity

The acute dermal toxicity of the test material was determined in accordance with the standardised guideline OECD 402, under GLP conditions. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The test material was applied as a single dermal dose to Wistar rats. A limit dose of 2000 mg/kg body weight was used as the starting dose. One female was dosed. Test material-related mortality was not observed during 48 hours. A total of three female rats were dosed with a limit dose of 2000 mg/kg body weight.

The test material applied to 3 females at a limit dose of 2000 mg/kg body weight did not cause death. The body weight of 2/3 females increased during the study, stagnation of body weight in one female was noticed. No signs of toxicity were observed at the dosage of 2000 mg/kg body weight during the first 4 hours or 14-day observation period. No dermal changes were observed. During necropsy no macroscopic findings were noticed.

Under the conditions of this study, the LD50 of the test material is greater than 2000 mg/kg body weight.

Acute Inhalation Toxicity

In accordance with column 2 of section 8.5.2 of REACH, the acute toxicity by inhalation study has been omitted as scientifically unjustified on the grounds that inhalation exposure to the substance is unlikely under normal conditions of use. The acute toxicity of the substance has been determined adequately by the oral and dermal routes.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to acute toxicity via the oral or dermal routes.