Anthraquinone

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

Materialy k obosnovaniju predelno dopustimoj koncentraciji antrachinona v vozduche rabocej zony

Author:

Volodchenko et al.

Year:

1970

Bibliographic source:

Gigiena Truda Prof. Zabol. 15(2), 58-29 (1971)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.29 (Sub-Chronic Inhalation Toxicity:90-Day Study)

Deviations:

yes

Remarks:

see the description below in the field "Principles of method if other than guideline"

Principles of method if other than guideline:

The rats were treated by dynamic inhalation introduction of Anthraquinone dust into the chamber, designed by I. F. Bojarčuk. The animals were exposed to Anthraquinone during 4 months, 5-6 hours daily. Atmospheric conditions were controlled by chemical method with sensitivity of 5 micrograms in 3 ml of assessed volume. Study was performed with doses 12.2±0.7 mg/m3 (the most frequently occuring exposure in production conditions) and 5.2±0.8 mg/m3.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Anthraquinone

EC Number:

201-549-0

EC Name:

Anthraquinone

Cas Number:

84-65-1

Molecular formula:

C14H8O2

IUPAC Name:

9,10-dihydroanthracene-9,10-dione

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

not specified

Sex:

not specified

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

The animals were exposed to Anthraquinone during 4 months, 5-6 hours daily.
Study was performed with doses 12.2±0.7 mg/m3 (the most frequently occuring exposure in production conditions) and 5.2±0.8 mg/m3.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Atmospheric conditions were controlled by chemical method with sensitivity of 5 micrograms in 3 ml of assessed volume.

Duration of treatment / exposure:

5-6 h

Frequency of treatment:

daily, 4 months in total

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

12.2 mg/m³ air (analytical)

Remarks:

Doses / Concentrations:
12.2±0.7 mg/m³
Basis:
analytical conc.

Doses / concentrations 2

Dose / conc.:

5.2 mg/m³ air (analytical)

Remarks:

Doses / Concentrations:
5.2±0.8 mg/m³
Basis:
analytical conc.

No. of animals per sex per dose:

total - 96 animals including control group

Control animals:

yes

Details on study design:

Functional state of the nervous system of animals was evaluated according to the general threshold indicator (S. V. Spěranskij): protein spectrum of blood serum, thymol test (Mac Lagan), the level of glycogen in the liver (Formol and Telete) provides information on the functional state of liver, the level of creatinine and residual nitrogen in blood indicated the functional state of kidneys. In addition, clinical blood tests were carried out with respect to regeneration (reticulogram) and degeneration (Heinz bodies, methemoglobin) in components of red blood cells and phagocytic activity of leukocytes. Irritation effect of substance on skin and mucous membranes of the eyes was also evaluated, and photodynamic effect was evaluated in a special series of experiments. Organs of killed animals were subject to histological analysis.

Examinations

Observations and examinations performed and frequency:

Anthraquinone at concentration of 12.2 mg/m3 had some effects on experimental animals: body weight loss, the level of hemoglobin was decreased to 76.2 and 74.4 % (97% in control group, P <0.05) at the end of 2nd and 4th month of exposure, decrease in the number of eryrthrocytes to 7.5 million (9.08 control trial, P <0.05) and relative reticulopenia. During the first 3 months of treatment the deficiency of vitamin C levels in blood in exposed animals was noted: basic level - 1 mg %, 1st month - 0.6 mg % (P <0.05), 2nd month - 0.45 mg %, 3rd month - 0, 39 mg %, in control experiment - 1 ÷ 0.8 mg %.
Concentration 5.2 ± 0.8 mg / m³: No significant changes.

Sacrifice and pathology:

Concentration 12.2 ± 0.7 mg / m³:
During histological analysis in the lungs of animals killed after treatment emphysema and atelectasis, cellular proliferation, in particular perivascular hyperemia of the capillaries and exsudation in the alveolar lumen. Blood picture was normalized during the experimental period, changes of the lung regenerated within the first month after termination of the experiment.

Concentration 5.2 ± 0.8 mg / m³:
No toxic effects of Anthraquinone were observed; Anthraquinone was regarded as ineffective in chronic experiment.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Haematological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

1

Key result

Dose descriptor:

NOEC

Effect level:

ca. 5.2 mg/m³ air (analytical)

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: no changes at this concentration

2

Dose descriptor:

other: Maximal Acceptance Concentration MAC

Effect level:

ca. 10 mg/m³ air

Based on:

test mat.

Sex:

not specified

Basis for effect level:

other: predicted value

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Executive summary:

The obtained experimental data allow to classify Anthraquinone as chemical dust of low toxicity, with no specific effect, because disturbance of trophic processes, tendency to reduce levels of hemoglobin and erythrocytes, deficiency of vitamin C in blood can be observed only when large quantities of dust are administered into the body (subacute test). Due to low toxicity of Anthraquinone, the observations in production combined with the experimental data allow to recommend a maximum permissible concentration of substance in the air of working area of 10 mg/m³.