3-methyl-6-(p-toluidino)-3H-dibenz[f,ij]isoquinoline-2,7-dione

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

traditional method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-methyl-6-[(4-methylphenyl)amino]-3H-naphthol[1,2,3-de]quinolone-2,7-dione

Cas Number:

81-39-0

Molecular formula:

C24H18N2O2

IUPAC Name:

3-methyl-6-[(4-methylphenyl)amino]-3H-naphthol[1,2,3-de]quinolone-2,7-dione

Test material form:

solid: particulate/powder

Specific details on test material used for the study:

Test item: Macrolex Rot 58
Purity: 99.4 %
Aggregation state: solid powder, red
Batch number: CHC002

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

A study on the acute inhalation toxicity of Macrolex Rot 58 (henceforward referred to as test item) on rats has been conducted in accordance with OECD Test Guideline no. 403 (2009). Test procedures were adapted so as to comply also with the Method B.2 of the Annex to Regulation (EC) No 440/2008, and especially OECD Guidance Document no. 39 (2009). One group of rats, consisting of 3 male and 3 female animals, was nose-only exposed to the solid aerosol of the test item at the maximum attainable concentration of 1175 mg/m3. Efforts have been made to meet the limit test criteria of the OECD Test Guideline no. 403 (2009). Animals were exposed to 1175 mg/m3 of an aerosol with a mean MMAD of 11.18 µm and mean GSD of 2.24. The generation of a test atmosphere with higher concentrations as well as lower MMAD was from a technical point of view not feasible, also using two other dust
generators. Furthermore micronization was not feasible as well. Thus 1175 mg/m3 was considered to be the highest technically feasible concentration with lowest achievable MMAD. Rats exposed to dry conditioned air only under otherwise identical circumstances served as controls.

Administration / exposure

Route of administration:

inhalation: mist

Type of inhalation exposure:

nose only

Vehicle:

clean air

Mass median aerodynamic diameter (MMAD):

11.18 µm

Geometric standard deviation (GSD):

2.24

Remark on MMAD/GSD:

The generation of a test atmosphere with higher concentrations as well as lower MMAD was from a technical point of view not feasible, also using two other dust generators. Furthermore micronization was not feasible as well. Thus 1175 mg/m3 was considered to be the highest technically feasible concentration with lowest achievable MMAD.

Details on inhalation exposure:

Three male and three female rats were simultaneously exposed under nose-only conditions for 4 h. This procedure is in compliance with the limit test described in OECD Test Guideline No. 403 and OECD GD#39 (2009).

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

1175 mg/m3

No. of animals per sex per dose:

3 males and 3 females

Control animals:

yes

Details on study design:

This procedure is in compliance with the limit test described in OECD Test Guideline No. 403 and OECD GD#39 (2009).

Statistics:

not applicable

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

discriminating conc.

Effect level:

1 175 mg/m³ air (analytical)

Based on:

act. ingr.

Exp. duration:

4 h

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

no

Clinical signs:

other: Test-item dependent red discoloration of the fur was observed at the head, forelegs, neck and thorax. No findings were seen at the functional observation battery.

Body weight:

No toxicological relevant test item-related changes in incremental body weight gain were observed.

Gross pathology:

No gross pathological findings were found in animals exposed to the test item.

Other findings:

Statistically comparisons between the control and the exposure groups revealed no significantly changed body temperatures at 1175 mg/m3 test item when compared to control groups.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Executive summary:

The mean mass median aerodynamic diameter (MMAD) was 11.18 µm and the mean geometric standard deviation (GSD) was 2.24. Animals exposed to the test item did not reveal any clinical symptoms. Nonetheless test-item dependent red discoloration of the fur was observed at the head, forelegs, neck and thorax. No findings were seen at the functional observation battery. No toxicological relevant test item-related changes in incremental body weight gain were observed. Statistically comparisons between the control and the exposure groups revealed no significantly changed body temperatures at 1175 mg/m3 test item when compared to control groups. Mortality did not occur at 1175 mg/m3. No gross pathological findings were found in animals exposed to the test item. In summary, the maximum attainable aerosol concentration was tested in this study.

The discriminating dose is >1175 mg/m3