1-hydroxy-4-[[4-[(methylsulphonyl)oxy]phenyl]amino]anthraquinone

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

05 October, 1993 to 17 November, 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

None

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-hydroxy-4-[[4-[(methylsulphonyl)oxy]phenyl]amino]anthraquinone

EC Number:

216-475-4

EC Name:

1-hydroxy-4-[[4-[(methylsulphonyl)oxy]phenyl]amino]anthraquinone

Cas Number:

1594-08-7

Molecular formula:

C21H15NO6S

IUPAC Name:

4-[(4-hydroxy-9,10-dioxo-9,10-dihydroanthracen-1-yl)amino]phenyl methanesulfonate

Test material form:

not specified

Details on test material:

None

Specific details on test material used for the study:

Test substance
Code number: FAT - 36038/F
En-Nr.: 409753.32
Purity 69.4 %
Appearance: solid
Solubility: insoluble
Storage: room temperature
Expiration date: 09/98

Test animals

Species:

rat

Strain:

other: Tif: RAI f (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited Animal Production 4332 Stein / Switzerland
- Weight at study initiation: 185 to 245 g
- Fasting period before study: overnight
- Housing: Macrolon cages type 4, with standardized soft wood bedding
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least for 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 10 %
- Air changes: approximately 15 air changes per hour
- Photoperiod: 12 hour/day light cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Distilled water

Details on oral exposure:

Administration of the test substance:one single oral dose, by gastric intubation (gavage)
Volume applied: 10 ml/kg bw

Doses:

2000 mg/kg bw (males and females)

No. of animals per sex per dose:

10 animals in total: 5 males and 5 females

Control animals:

no

Details on study design:

- Mortality: daily; a.m. and p.m. on working, days, a.m. on weekend days.
- Signs and symptoms: daily for 14 days
- Body weight: immediately before administration and on days 7 and 14
- Necropsies: The animals were submitted to a gross necropsy at the end of the observation period.
- Other examinations performed: clinical signs, body weight.

Statistics:

No data

Results and discussion

Preliminary study:

None

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occurred in this study.

Clinical signs:

other: Piloerection, hunched posture and dyspnoea were seen, being common symptoms in acute tests. Additionaly, reduced locomotor activity was observed in the females. The animals recovered within 6 days.

Gross pathology:

At necropsy, no deviations from normal morphology were found in all animals.

Other findings:

None

Any other information on results incl. tables

In-life observations:

	Administartion day			Day after administration
Animal N° observations	1 hrs	3 hrs	5 hrs	1	2	3	4	5	6	7	8
2000 mg/kg, males
1 -5 piloerection	+	+	++	++	+	+	+	+
1 -5 hunched posture	++	++	++	+	+
1 -5 dyspnea	+	+	+	+
2000 mg/kg, females
1 -5 piloerection	+	++	++	+	+	+	+	+
1 -5 hunched post	+	+	+	+	+	+
1 -5 dyspnea	+	+	+	+
1 -5 red. locom. act.		+	+

+ = slight, ++ = moderate, +++ = severe

hunched post = hunched posture

red.locom.act= reduced locomotor activity

Body weight and necropsy findings:

Animal number	Body weight (g) d0	Body weight (g) d7	Body weight (g) d14	*	Gross necropsy findings
2000 mg/kg, males
1	239	302	335	TS	NOA
2	245	317	367	TS	NOA
3	240	301	336	TS	NOA
4	241	303	345	TS	NOA
5	243	299	333	TS	NOA
Mean	242	304	343
SD	2.4	7.2	14.1
2000 mg/kg, females
1	205	227	241	TS	NOA
2	203	240	243	TS	NOA
3	185	210	222	TS	NOA
4	200	222	229	TS	NOA
5	189	213	225	TS	NOA
Mean	196	222	232
SD	8.9	12.0	9.5

* TS: terminal sacrifice

NOA: no observable abnormalities

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 for FAT 36038/F was found to be greater than 2000 mg/kg bw.

Executive summary:

The acute oral toxicity of FAT 36038/F was assessed in albino rats according to the test guidelines OECD 401 and 92/69/EEC, B.1.

A group of ten rats (5 males and 5 females) was treated by oral gavage at dose level of 2000 mg/kg bw. Prior to dosing by gastric intubation, the animals were fasted overnight. After administration, the animals were observed daily for clinical signs and mortality. Body weight was recorded immediately before administration, on day 7 and day 14. At the end of the observation period, the animals were observed for a gross necropsy at the end of the study period.

Results:

Mortality: No deaths occurred during the test.

Signs of toxicity: Piloerection, hunched posture and dyspnea were seen, being common symptoms in acute tests.Additionally, reduced locomotor activity was observed in the females. The animals recovered within 6 days.

Body weight: No effect on body weight gain was seen.

Effects in organs: At necropsy, no deviations from normal morphology were found in all animals.

Thus, upon an acute oral administration and a 14 day post-treatment observation period, the LD50 for FAT 36038/F was found to be greater than 2000 mg/kg bw.