1,4-bis(mesitylamino)anthraquinone

Repeated dose toxicity: inhalation

Administrative data

Endpoint:

sub-chronic toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

4 (not assignable)

Data source

Reference

Reference Type:

publication

Title:

WATER QUALITY CRITERIA FOR COLORED SMOKES: ) SOLVENT GREEN 3

Author:

Kowetha A. Davidson Patricia S. Hovatter

Year:

1987

Bibliographic source:

Chemical Effects Information Task Group Information Research and Analysis Section Health and Safety Research Division

Materials and methods

Principles of method if other than guideline:

90 days subchronic repeated dose toxicity study of 1,4-bis(p-tolylamino)anthraquinone (CI Solvent Green 3) in rat was conducted to evaluate adverse effects by inhalation route.

GLP compliance:

not specified

Test material

Test material information

1

Reference substance name:

1,4-bis(p-tolylamino)anthraquinone

EC Number:

204-909-5

EC Name:

1,4-bis(p-tolylamino)anthraquinone

Cas Number:

128-80-3

Molecular formula:

C28H22N2O2

IUPAC Name:

1,4-bis[(4-methylphenyl)amino]-9,10-anthraquinone

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male/female

Details on test animals or test system and environmental conditions:

Details on test animal
TEST ANIMALS
- Source: Inhalation Toxicology Research institute
- Age at study initiation: 15-20 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: Hazleton 2000 exposure chambers in the Chronic Exposure Laboratory.
- Diet (e.g. ad libitum): Wayne Lab Blox ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 2 to 3 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 75 +/- 30F
- Humidity (%): 35-70 %
- Air changes (per hr):no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

whole body

Vehicle:

not specified

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Jet-O-Mizer air jet mill
- Method of holding animals in test chamber: Four Hazleton 2000 chambers containing 6 tiers of animal cages (10-16 rats per tier) were used for these wholebodyinhalation exposure studies.
- Source and rate of air: no data
- Method of conditioning air: no data
- System of generating particulates/aerosols: Jet-O-Mizer air jet mill
- Temperature, humidity, pressure in air chamber: monitored throughout this study
- Air flow rate: no data
- Air change rate: no data
- Method of particle size determination: LovelaceMulti-Jet cascade impactor
- Treatment of exhaust air: no data

TEST ATMOSPHERE
- Brief description of analytical method used:no data
- Samples taken from breathing zone: no data

VEHICLE (if applicable)
- Justification for use and choice of vehicle: no data
- Composition of vehicle: no data
- Type and concentration of dispersant aid (if powder): no data
- Concentration of test material in vehicle: no data
- Lot/batch no. of vehicle (if required): no data
- Purity of vehicle: no data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

90 days

Frequency of treatment:

6 hours/day, 5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1, 10,and 100 mg/m3
Basis:

No. of animals per sex per dose:

392 rats (196 males and 196 females)

Control animals:

yes

Details on study design:

These concentrations were selected on the basis of the results from the 4-weeks exposures to solvent green 3 dye

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: No data

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Detailed clinical observations were also done at 6 weeks after the initiation of exposures, at the end of the 90 day exposures and after the 30 day recovery period. The animals were also observed twice daily for morbidity and mortality.

BODY WEIGHT: Yes
During this 3-month exposure, subsets of both male and female rats from each exposure chamber were
weighed on a weekly basis.

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: / No data

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): No data

OPHTHALMOSCOPIC EXAMINATION: Yes / No / No data
- Time schedule for examinations:
- Dose groups that were examined:

HAEMATOLOGY: Yes
Hematology measurements were made on 12 control rats and 12 rats at each concentration at the end of the 90-day exposure and after a 30 day recovery period

CLINICAL CHEMISTRY:
Clinical chemistry measurements were made on 12 control rats and 12 rats at each concentration at the end of the 90-day exposure and after a 30 day recovery period

URINALYSIS: No data

NEUROBEHAVIOURAL EXAMINATION: No data

OTHER:
Lung Content of 01 and TA After Exposure to SY/SG Dye
At the end of the 3-month exposure, six rats (3 males and 3 females) from eact chamber were sacrificed. Following each sacrifice, lungs were removed, homogenized in acetonitrile, the homogenate centrifuged, and the supernatant removed. The tissue pellet was then re-extracted with acetonitrile until no more dye was removed. The pooled acetonitrile extracts were analyzed for the major chemicals in the SY/SG dye mixture

Respiratory Function Measurements
Respiratory function data from measurements of rats before exposures, immediately after exposures and 30 days after exposure; to SY/SG dye were analyzed

Lung Biochemistry
Bronchoalveolar lavage fluid (BAL) was analyzed for indicators of injury after 6 and 13 weeks of exposure and after 30 days of recovery from the exposure

Lung Connective tissue Biochemistry
The collagen contents of bronchoalveolar fluid and of lung tissue were determined at the end of the 90 day exposure and after a 30-day recovery period

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes
Ten males and ten females from each exposure and time were sacrificed by intraperitoneal injections with T61 and examined for gross lesions. Routine parafin embedded, 5 micron, hematoxylin and eosin stained slides from the following tissues were prepared for all animals: skin, tracheobronchial lymph node, popliteal lymph node, spleen, femur, larynx, nasal cavity (four levels), trachea, lung (four lobes), heart, stomach, duodenum, cecum, colon, liver, pancreas, kidneys, urinary bladder, epididymis, testis, prostate, uterus, ovary, adrenal, thyroid, brain, pituitary, eyes, and any gross lesions.

Statistics:

Computer software packages such as BMDP or RSl were used for data handling and analysis. Standard tests applied to the experimental data were one-way analyses of variance, followed by tests for the equality of 4 means, such as simple t-tests, multiple comparison t-tests, or non-parametric Mann-Whitney U tests. Usually a confidence level of 0.05 was used, although in some cases significance was expressed in much smaller or much larger values.

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Description (incidence and severity):

no mortalities observed

Mortality:

no mortality observed

Description (incidence):

no mortalities observed

Body weight and weight changes:

no effects observed

Description (incidence and severity):

no statistically significant differences in the weights of female rats

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

not specified

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

not specified

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not specified

Effect levels

Dose descriptor:

NOAEL

Effect level:

1 mg/m³ air

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Effects: no mortalities observed,no statistically significant differences in the weights of female rats.

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The No observed adverse effect level (NOAEL)of Solvent green 3 (yellow /green dye) in F344/Crl rats in 90 days study was observed at dose concentration of 1 mg/m3 air.

Executive summary:

The purpose of this study was to evaluate the toxicity ofSolvent green 3 (yellow /green dye) inF344 ratsby repeated inhalation exposure for 90 days.Male and female F344 rats were exposed to inhalation0, 1,10 and 100 mg/m3 of SY/SG dye aerosol for6hr/day, 5 days/wk for 90 days. After exposures, it was found that no mortalities were observed at any of the dose level, there were no statistically significant differences in the weights of female rats among the four groups, while those of male rats exposed to the highest level of SY/SG dye remained significantly lower than male control animal weights. There were no significant differences between pre-exposure data from control or treated rats. There were no physiologically meaningful differences between respiratory function of treated and control rats at theend of exposure.An inflammatory response in the lungs was observed at highest concentration. Histopathological changes were observed at highest dose group. Hence the NOAEL was considered to be 1 mg/m3