1-hydroxy-4-(p-toluidino)anthraquinone

Endpoint summary

Description of key information

Several acute oral toxicity studies are available. In the key study a single dose of 5000 mg/kg bw of the test substance was applied to 5 male and 5 female Wistar rats per gavage. The dose of 5000 mg/kg body weight was tolerated without signs of poisoning by all male and female animals. Necropsy of some animals sacrificed at the end of study showed no adverse gross pathological findings. The LD50 is greater than 5000 mg/kg bw (discriminating dose).

In the other acute oral toxicity studies LD50 values greater than 5000 mg/kg bw, 10000 mg/kg bw or 2000 mg/kg bw (discriminating dose each) were found.

A study was performed to assess the acute inhalation toxicity of the test item. The method used was designed to be compatible with that described in the OECD Guideline for Testing of Chemicals (2009) No. 436 "Acute Inhalation Toxicity- Acute Toxic Class Method" and Method B.52. Acute Inhalation Toxicity-Acute Toxic Class Method, 2014, of Commission Regulation (EC) No. 440/2008. The properties of Macrolex Violett B were shown to be unfavorable to produce a suitable test atmosphere. Mechanical systems designed to produce dust aerosols were unsuccessful in producing a suitable test atmosphere with a particle size that would have been in full compliance with the inhalation test guidelines. It was, therefore, considered to be not possible to generate a suitable test atmosphere from the test item, for use in an inhalation study.  In view of the physical nature of the test item and its apparent low volatility, it is considered unlikely to represent a significant hazard by the inhalation route.

According to Commission Regulation (EU) 2016/863 of May 2016 acute toxicity testing by the dermal route (Annex VII, point 8.5.3., column 2) ‘does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure’.  The registered substance conforms with the requirements given above. Therefore, it can be concluded for acute dermal toxicity that the available information is conclusive for non-classification.  

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

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

A single dose of 5000 mg/kg bw of the test substance was applied to 5 male and 5 female Wistar rats per gavage. The animals were inspected several times on the day of administration, and twice daily during the following 14-day observation
period (once on weekends and bank holidays). During inspections, the type, onset, duration, and intensity of clinical signs were recorded and dead animals removed if necessary. The animals were individually weighed at application, after one week and at the end of the 14-day observation period. Animals sacrificed at the end of study were randomly necropsied.

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

The acute toxicity experiment was carried out with SPF-bred Wistar rats (strain Bor: WISW (SPF Cpb). At the start of study the male rats were about 9 weeks old and females 14 weeks; the mean initial weight of males was 180 and that of females 158 g.
The rats were housed in groups of five animals each under conventional conditions in Makrolon Type-III cages on dust-free wood granules; they were exposed to a room temperature of 22 ± 1.5° C, a 12-hour light/dark cycle (artificial light from 7 a.m. to 7 p.m. CET), and relative humidity of about 60 ± 5 %.
During the study period the animals received tap water ad libitum. Feed was withdrawn from approx. 16 hours prior to until approx. 4 hours after application. The other time it was available ad libitum.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

The substance was formulated in polyethylene glycol and once administered with a rigid metal gavage to 5 male and 5 female animals at an application volume of 20 ml/kg body weight.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female rats/dose

Control animals:

no

Details on study design:

The animals were inspected several times on the day of administration, and twice daily during the following 14-day observation period (once on weekends and bank holidays). During inspections, the type, onset, duration, and intensity of clinical signs were recorded and dead animals removed if necessary. The animals were individually weighed at application, after one week and at the end of the 14-day observation period. Animals sacrificed at the end of study were randomly necropsied.

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred.

Clinical signs:

other: Single administration of 5000 mg/kg was tolerated by all animals without clinical signs of toxicity.

Gross pathology:

Necropsy of some animals sacrificed at the end of study showed no unusual gross pathological findings.

Interpretation of results:

GHS criteria not met

Conclusions:

The LD50 was greater than 5000 mg/kg bw (discriminating dose).

Executive summary:

A single dose of 5000 mg/kg bw of the test substance was applied to 5 male and 5 female Wistar rats per gavage. The animals were inspected several times on the day of administration, and twice daily during the following 14-day observation period (once on weekends and bank holidays). During inspections, the type, onset, duration, and intensity of clinical signs were recorded and dead animals removed if necessary. The animals were individually weighed at application, after one week and at the end of the 14-day observation period. Animals sacrificed at the end of study were randomly necropsied. The dose of 5000 mg/kg body weight was tolerated without signs of poisoning by all male and female animals. Necropsy of some animals sacrificed at the end of study showed no adverse gross pathological findings. The LD50 is greater than 5000 mg/kg bw (discriminating dose).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Quality of whole database:

Equivalent or similar to OECD Guideline 401 (Acute Oral Toxicity).

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

In all available acute oral toxicity studies a LD50 > 2000 mg/kg bw was found (discriminating dose). The conduction of an acute inhalation toxicity study was not possible, because the properties of Macrolex Violett B were unfavorable to produce a suitable test atmosphere. According to Commission Regulation (EU) 2016/863 of May 2016 acute toxicity testing by the dermal route (Annex VII, point 8.5.3., column 2) ‘does not need to be conducted if the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route and no systemic effects have been observed in in vivo studies with dermal exposure’.  The registered substance conforms with the requirements given above. Therefore, it can be concluded for acute dermal toxicity that the available information is conclusive for non-classification.  

According to CLP classification criteria (Regulation (EC) No 1272/2008) a classification is therefore not justified.