Tetramethyl 2,2'-[1,4-phenylenebis[imino(1-acetyl-2-oxoethane-1,2-diyl)azo]]bisterephthalate

Endpoint summary

Description of key information

Oral: LD50 > 2000 mg/kg bw/day, OECD 423

Inhalative (dust): LC50 (4h, rat) > 1.7 mg/L air (highest concentration possible), OECD 403; read-across with CAS 5580-57-4

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:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

- Lot/batch No.: T05003
- Expiration date of the lot/batch: 17 June 2000
- Stability under test conditions: stable in vehicle for at least 96 h
- Storage condition of test material: at room temperature in the dark

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Sulzfeld, Germany.
- Age at study initiation: approx. 8 weeks old
- Weight at study initiation: average 274 g (males) and 193 g (females)
- Fasting period before study: overnight
- Housing: 3 animals per sex per cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 1997-07-30 To:1997-08-15

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: adjusted for body weight
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: pre-test and stability

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weight days 1 (pre-administration), 8 and 15. Viability was checked twice daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs (at periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15)

Statistics:

Not needed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality observed

Mortality:

None

Clinical signs:

other: Hunched posture and uncoordinated movements were noted in the majority of animals. The animals had recovered from the symptoms between days 2 and 3, except for one female, which showed hunched posture up to day 4 and on day 12.

Gross pathology:

No findings

Other findings:

Yellow staining of the skin by the test substance was noted in all animals between days 3 and 8.

Interpretation of results:

GHS criteria not met

Executive summary:

The pigment was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed. Hunched posture and uncoordinated movements were noted in the majority of animals. The animals had recovered from the symptoms between days 2 and 3, except for one female, which showed hunched posture up to day 4 and on day 12. Yellow staining of the skin by the test substance was noted in all animals between day 3 and 8. Body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found in the animals at macroscopic post mortem examination.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

READ ACROSS ANALOGUE APPROACH
Please find the complete Read-across justification text attached below.

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 1.7 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: No mortality and clinical signs

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating conc.

Value:

1 700 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

5 000 mg/kg bw

Additional information

Oral:

 There are reliable data available to assess the acute oral and dermal toxicity of the test substance. The studies were performed in 1997 when characterization of powders in regard to particles with a size of < 100 nm was not routinely performed. Doses applied exceeded the maximum doses later prescribed in OECD testing guidelines. Retrospective analysis did not allow any conclusion on whether the test material was a a nanomaterial or not. However, organic pigments are all powders that often have a nanosize fraction. They consistently show absence of a hazard if tested up to the limit dose in studies with oral and dermal dosing (Stratmann, et al. Indicators for lack of systemic availability of organic pigments, https://doi.org/10.1016/j.yrtph.2020.104719, Regulatory Toxicology and Pharmacology Volume 115, August 2020, 104719). The publication lists 113 and 35 pigments tested for acute oral and dermal toxicity, respectively and in none of the studies, treatment-related morbidities were observed. Therefore, the available experimental data is considered adequate to assess the hazard of the pigment both in the bulk and in the nano form.

The acute oral toxicity of the test substance in rats was determined in a study according to OECD guideline 423 (Clariant, 1997). The pigment was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg body weight. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed. No mortality occurred. Hunched posture and uncoordinated movements were noted in the majority of animals. The animals had recovered from the symptoms between days 2 and 3, except for one female, which showed hunched posture up to day 4 and on day 12. Yellow staining of the skin by the test substance was noted in all animals between day 3 and 8. Body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found in the animals at macroscopic post mortem examination. The determined LD50 value is above 2000 mg/kg bw, which is the upper limit of classification.

Inhalation:
In an acute inhalation toxicity study (similar to OECD 403, Ciba-Geigy Ltd., 1976), groups of Tif:RAIf rats (9/sex) were exposed to dust of the test substance (CAS 5580-57-4) for 4 hours and observed for 14 days. No mortality occurred during 14 day observation. At concentrations of 1700 mg/m³ air at the 4 hour exposure the animals showed no toxic symptoms. At autopsy, no deviations from normal morphology were found in all animals. 1700 mg/m³ air was the highest possible concentration. That leads to an LC50 greater than 1700 mg/m³ air at 4 hour exposure. As no lethal effects occurred at the maximum technically feasible concentration it is concluded that the members of the 'yellow disazo condensation pigments' have not to be classified for acute toxicity after inhalation exposure.

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No 1272/2008
The available experimental test data are reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. Based on available data on acute toxicity, the test item is not classified according to Regulation (EC) No 1272/2008 (CLP).