1-amino-4-hydroxy-2-(2-phenoxyethoxy)anthraquinone

Endpoint summary

Description of key information

Kuthy 2021

Under the conditions of this study, the LD50 of the test material was found to be >5000 mg/kg bw in rats.

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:

12 May 2021 to 28 May 2021

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: 10-11 weeks (first and second step)
- Weight at study initiation: 198 - 208 g (first step); 206 - 207 g (second step)
- Fasting period before study: Yes (The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.)
- Housing: Group caging (3 animals/cage). Type III polypropylene/polycarbonate cage.
- Diet: ad libitum
- Water: tap water from municipal supply, ad libitum
- Acclimation period: 27 days (first step); 28 days (second step)

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: above 10 air exchanges/hour
- Photoperiod: 12 hours light daily, from 6.00 a.m. to 6.00 p.m.

Route of administration:

oral: gavage

Vehicle:

other: Helianthi annui oleum raffinatum

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): treatment volume of 10 mL/kg bw
- Justification for choice of vehicle: not specified

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

DOSAGE PREPARATION
Formulations were prepared just before the administration and were stirred continuously during the treatment.

CLASS METHOD
The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animals died in first step, so further three female rats were treated with the same dose. No animals died in second step, too, so the test was finished, because the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

Doses:

2000 mg/kg bw (female)

No. of animals per sex per dose:

3 animals per group

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually (for mortality) after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each day for 14 days thereafter. Their general state, external appearance, behaviour and clinical symptoms were also assessed individually. Indeed, individual observations were performed on the skin and fur, eyes and mucous membranes and also respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Necropsy of survivors performed: Yes (necropsy on the treatment day and Day 15)
After examination of the external appearance, the cranial, thoracic and abdominal cavities were opened and the appearance of the tissues and organs was observed, and any abnormality was recorded with details of its location, colour, shape and size.
- Other examinations performed: The body weights were also recorded on day 0 (just before the treatment), on day 1, on day 7 and on day 15 with a precision of 1 g.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No death occurred after the single 2000 mg/kg bw oral dose of the test material

Mortality:

No death occurred at 2000 mg/kg bw single oral dose of the test material. All female rats in step 1 and step 2 survived until the end of the 14-day observation period.

Clinical signs:

other: no treatment related symptoms were observed throughout the 14-day post-treatment period

Body weight:

other body weight observations

Remarks:

The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.

Gross pathology:

All animals treated with 2000 mg/kg bw dose survived until the scheduled necropsy on Day 15. No pathological changes were found related to the effect of the test material during the macroscopic examination of animals treated with 2000 mg/kg bw dose.

Other findings:

No death occurred after the single 2000 mg/kg bw oral dose of test material. There were no toxic clinical signs and no test material related effect found in body weights and body weight gains during the study. Autopsy revealed no treatment related pathological changes.

Overall results

Dose (mg/kg bw)	Mortality (dead/treated)	LD50 (mg/kg bw)	GHS category
2000	0/6	above 5000	5 or unclassified

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, the LD50 of the test material was found to be >5000 mg/kg bw in rats.

Executive summary:

The acute oral toxicity of the test material was investigated according to OECD Guideline 423 in accordance with GLP using the acute toxic class method. This method involved a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animals died in the first step, so a further three female rats were treated with the same dose. No animals died in second step, too, so the test was finished, because the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

Therefore, under the conditions of this study, the LD50 of the test material was found to be >5000 mg/kg bw in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 5 000 mg/kg bw

Quality of whole database:

The endpoint is addressed with a guideline study that was conducted under GLP conditions. The quality of the submitted data for this endpoint is therefore considered to be high.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute oral toxicity of the test material was investigated according to OECD Guideline 423 in accordance with GLP using the acute toxic class method. The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The acute toxic class method involved a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animals died in the first step, so a further three female rats were treated with the same dose. No animals died in second step, too, so the test was finished, because the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

Therefore, under the conditions of this study, the LD50 of the test material was found to be >5000 mg/kg bw in rats.

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 oral toxicity.