Reaction mass of 1,4-bis(methylamino)anthraquinone and 1,4-bis[(2-ethylhexyl)amino]anthraquinone and 1-[(2-ethylhexyl)amino]-4-(methylamino)anthraquinone and 9,10-Anthracenedione, 1,4-bis(pentylamino)-, branched and linear and 9,10-Anthracenedione, 1-(methylamino)-4-(pentylamino)-, branched and linear and 9,10-Anthracenedione, 1-[(2-ethylhexyl)amino]-4-(pentylamino)-, branched and linear

Endpoint summary

Description of key information

Reliable acute oral toxicity assay in rats.

Disregarded oral and dermal acute studies (rats and rabbits respectively)

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:

5-6-1982 to 5-20-1982

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: OECD guideline study performed in accordance with GLP; exact details of test material (certificate of analysis, Characterisation) are not included in the report.

Qualifier:

according to guideline

Guideline:

other: OECD Guidelines For Testing-of Chemicals, 1981

Deviations:

not specified

GLP compliance:

yes

Test type:

other:

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Five male and five female young adult Sprague-Dawley rats were purchased from Charles River Breeding Laboratories, Wilmington, MA. After an acclimation period of at least 5 days, animals were assigned to the test. Animals were individually housed in wire mesh bottom cages in environment controlled rooms as per "Guide for the Care and Use of Laboratory Animals" DREW Publication No. (NIH) 78-23.

Housing: Animals will be individually housed in wire mesh bottom cages When placed on study.
Food: NIH open formula 07, certified feed (Zeigler, Bro., Gardners, PA») ad libitum. No known cntaminants are expected to be present in the basal diet that would interfere with the conduct of this study.
Water: Tap water, ad libitum. Water is monitored for contaminants at periodic intervals according to FDRL Standard Operating Procedures.
Environment: All animals will be housed in environment controlled rooms as per "Guide for the Care and Use of Laboratory Animals". Filtered air will be supplied to provide 12-15 air changes per hour. A 12 hour light-dark cycle will be maintained.
Quarantine: Minimum of 5 days. During this conditioning period, the animals will be observed for any clinical signs of disease. All animals with any evidence of disease or physical abnormalities will be discarded.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

Dosing:
Animals were fasted overnight (approximately 18 hours) prior to receiving a single oral dose of 5.0g/kg of the test article. The test article was administered at a constant concentration and prepared just before use.

Concentration prepared: 50% w/v
Diluent: Corn Oil
Total amount dispensed: 40 ml
Prepared physical state: Solution

Doses:

5.0 g/kg body weight

No. of animals per sex per dose:

5 male and 5 female per dose

Control animals:

no

Details on study design:

All animals were observed for at least 14 days or until all signs of reversible toxicity subsided, whichever occurred later. They were observed three times a day on the day of dosing and twice daily for the remainder of the study. Cageside observations included changes in the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea, lethargy sleeps and coma. All gross or visible toxic or pharmacological effects were recorded. Body weights were recorded initially and on days 8 and 15 or at death. All animals that died, and all survivors that were sacrificed at termination of the study were subjected to a gross necropsy. All abnormalities were recorded.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

95% CL:

0 - 27

Mortality:

There was 0% mortality in the study.

Clinical signs:

other: Clinical observations: Males - Decreased activity in all 5 males. No deaths. Females - Decreased activity in all 5 females. Ataxia observed in all 5 females. No deaths.

Gross pathology:

Necropsy Observations:
Males - Fatty tissue and hypodermis appeared to have absorbed test article in all 5 males.
Females - Fatty tissue and hypodermis appeared to have absorbed test article in all 5 Females.

Bodyweight and Dosing Data

	Body weight (g) at Day
Animal number and sex	1	8	15	Level Dosage g/kg	Dose (ml)
21 (M)	319	348	370	5.0	3.19
22 (M)	297	328	360	5.0	2.97
23 (M)	322	356	378	5.0	3.22
24 (M)	313	348	374	5.0	3.13
25 (M)	310	330	344	5.0	3.10
26 (F)	268	296	304	5.0	2.68
27 (F)	230	250	258	5.0	2.30
28 (F)	252	267	284	5.0	2.52
29 (F)	220	233	238	5.0	2.20
30 (F)	238	252	256	5.0	2.38

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

No mortality was observed in the treated rats. The acute oral LD50 of the test material was determined to be greater than 5.0g/kg body weight in male and female Sprague-Dawley rats.

Executive summary:

An acute oral toxicity study was conducted using male and female Sprague-Dawley rats given a single oral dose of 5.0 g/kg body weight. No mortality was observed in the treated rats. Body weights increased in all animals during the study. Clinical observations included decreased activity in all animals as well as ataxia observed in all of the females. At necropsy, it was observed in all of the animals that the fatty tissue and hypodermis appeared to have absorbed the test article. The acute oral LD50 of the test material was determined to be greater than 5.0 g/kg body weight.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

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

Acute oral toxicity:

An acute oral toxicity study was conducted using male and female Sprague-Dawley rats given a single oral dose of 5.0 g/kg body weight. No mortality was observed in the treated rats. Body weights increased in all animals during the study. Clinical observations included decreased activity in all animals as well as ataxia observed in all of the females. At necropsy, it was observed in all of the animals that the fatty tissue and hypodermis appeared to have absorbed the test article. The acute oral LD50 of the test material was determined to be greater than 5.0 g/kg body weight.

A second Oral acute toxicity study is available for this substance. However it was performed by Industrial Biotest at a time when there were known to be major concerns about fraudulent testing practices. In addition, the specific details of the substance tested (e.g. whether it contained only the registered substance or if it also contained solvent) are not clear from the limited report.. Consequently this study was disregarded and the more recent reliable study used as the key study. It should be noted that the results of this study do agree with the results from the key study, with the LD50 > 5g/kg bw.

Acute Dermal toxicity:

The only study available for this endpoint was performed by Industrial Biotest at a time when there were known to be major concerns about fraudulent testing practices. In addition, the specific details of the substance tested (e.g. whether it contained only the registered substance or if it also contained solvent) are not clear from the limited report. Consequently this study was disregarded. However, it should be noted that the LD50 was far in excess of 2 g/kg bw and given the low oral toxicity potential and limited dermal bioavailability (refer to TK section), a repeat of this study was not required.

Justification for classification or non-classification

Criteria for classification are not met.