1-amino-4-hydroxy-2-phenoxyanthraquinone

Endpoint summary

Description of key information

LD50 (oral) = ca. 7000 mg/kg bw, equivalent to 2772 mg/kg bw of active ingredient.

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:

April 13th, 1978

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: RAIf (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 160 - 180 g
- Fasting period before study: overnight
- Housing: 5 animals per Macrolon cage (type 3)
- Diet: Rat food - NAFAG, Gossau SG, ad libitum
- Water: water ad libitum
- Acclimatization period: 4 days minimum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1
- Humidity (%): 55 ± 5
- Photoperiod (hrs dark / hrs light): 10 hours light cycle day

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

2 %

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50 %
- Other: The test substance was suspended in the vehicle. Before treatment, the suspension was homogenously dispersed with an Ultra-Turrax and during treatment, it was kept stable with a magnetic stirrer.

OTHER
No higher doses than those administered were possible

Doses:

3170, 4640, 6000 and 7750 mg/kg bw

No. of animals per sex per dose:

5 males and 5 females per dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: 1 hour, 24 hours, 48 hours, day 7 and day 14. The physical condition and rate of deaths of animals was monitored throughout the whole observation period
- Necropsy of survivors performed: yes. They were subjected to a necropsy whenever they died. Survivors were subjected to necropsy at the end of the observation period

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 7 000 mg/kg bw

Based on:

test mat.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 772 mg/kg bw

Based on:

act. ingr.

Mortality:

These were the mortalities which occurred during the study:
- in the 6000 mg/kg bw group, 1 female mortality occurred after 7 d, and
- in the 7750 mg/kg bw group, 3 male mortalities and 1 female mortality occurred after 24 h.

Clinical signs:

other: Within 2 hours of treatment, the rats in the dosage groups showed sedation, dyspnoea, exophthalmos, curved position, diarrhoea and ruffled fur. Surviving animals recovered within 8 to 11 d.

Gross pathology:

No substance-related gross organ changes were seen.

Interpretation of results:

other: not classified according to the CLP Regulation (EC 1272/2008)

Conclusions:

LD50 = ca. 7000 mg/kg bw, equivalent to 2772 mg active ingredient/kg bw.

Executive summary:

The potential of the substance for acute toxicity following oral administration was tested in male and female rats of the RAIf (SPF) strain. 5 animals per sex per dose were tested at doses of 3170, 4640, 6000 and 7750 mg/kg bw and observed for 14 days.

Within 2 hours of treatment, the rats in the dosage groups showed sedation, dyspnoea, exophthalmos, curved position, diarrhoea and ruffled fur. Surviving animals recovered within 8 to 11 days. They were subjected to a necropsy whenever they died. Survivors were subjected to necropsy at the end of the observation period. In the 6000 mg/kg bw group, 1 female mortality occurred after 7 d, and in the 7750 mg/kg bw group, 3 male mortalities and 1 female mortality occurred after 24 h. The LD50 of the test substance was determined to be approximately 7000 mg/kg bw.

Based on the active ingredient content, namely 2772 mg/kg bw, the test substance is not classified as acutely toxic by oral exposure route.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 772 mg/kg bw

Quality of whole database:

The study is comparable to a guideline study. The tested substance is of the highest purity compared to other available tests.

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 potential of the substance for acute toxicity following oral administration was tested in male and female rats of the RAIf (SPF) strain. 5 animals per sex per dose were used in tests conducted in 1980, 1978, 1977 and 1976. The observation period was 14 days in all tests.

Signs and symptoms seen in rats included sedation, diarrhoea, dyspnoea, ruffled fur and curved position. Clinical symptoms resolved between 8 - 11 days in the tests of 1980, 1978 and 1976. Animals were subjected to necropsy whenever they died or at the end of the test. Substance-related organ changes were not seen in autopsies.

The LD50 of the test substance was determined to be approximately ca. 7000 mg/kg bw in the chosen test, equivalent to 2772 mg active ingredient/kg bw. The chosen test (1978) is comparable to a guideline study. The tested substance in this study has the highest purity (39.6 %) compared to the other available tests.

However, LD50 values from other tests were available, far above the threshold limit of 2000 mg/kg bw of active ingredient set in the CLP Regulation (EC n. 1907/2006). In one study (1980) no LD50 was determined, as the highest tested concentration of 5000 mg/kg bw or 1665 mg/kg bw of active ingredient, was identified as LD20.

Justification for classification or non-classification

The CLP Regulation (EC 1272/2008), Annex I, Part 3, Table 3.1.1 gives the following criteria for acute oral toxicity: "Category 4: 300 < ATE ≤ 2 000," where ATE is acute toxicity estimates in mg/kg bodyweight.

Based on the active ingredient content, LD50 of the test substance was determined to be ca. 2772 mg/kg bw in the chosen reference test, which is outside the above criteria.

Therefore, the test substance is not acutely toxic by the oral exposure route.