Phenol, 4-[[4-(dimethylamino)phenyl]azo]-, reaction products with sodium sulfide (Na2(Sx)), leuco derivatives

Endpoint summary

Description of key information

In an acute oral toxicity study in rats the acute oral LD50 was determined to be > 2000 mg dye/kg bw (corresponding to > 2280 mg product/kg bw).

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

Study period:

07 December 2016 - 16 March 2017

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)

Version / remarks:

2001

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Species and strain: Crl:WI rats
Source: TOXI COOP ZRT. Cserkesz u. 90., 1103 Budapest, Hungary
Hygienic level at arrival: SPF
Hygienic level during the study: Good conventional
Justification of strain: The Wistar rats as a rodent is one of the standard species of acute toxicity studies
Number of animals: 3 animals/group
Sex: Female, nulliparous and non pregnant animals
Age of animals: Young adult rat, 8 weeks old in first and second step
Body weight range
at starting (first step): 217 - 219 g
Body weight range
at starting (second step): 217 - 218 g
Acclimatization time: 6 days in the first step and 7 days in the second step

Housing: Group caging (3 animals/cage)
Cage type: Type II polypropylene/polycarbonate.
Bedding: Laboratory bedding.
Light: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: above 10 air exchanges/hour by central air-condition system.

Animals received ssniff® SM R/M-Z+H complete diet for rats and mice produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany
and tap water from municipal supply, as for human consumption from bottle ad libitum.

Route of administration:

oral: gavage

Vehicle:

water

Remarks:

Aqua purificata Ph.Hg. VIII.

Details on oral exposure:

All doses were formulated in the vehicle. Concentration of formulations was adjusted to maintain a treatment volume of 10 mL/kg bw. The test item was applied in a concentration of 200 mg/mL. The correction factor (1.14) was taken into consideration in the course of the making of solution. Formulations were prepared just before the administration and were stirred continuously during the treatment.

Vehicle:
Name: Aqua purificata Ph.Hg. VIII.
Batch number: 1608-5511
Date of expiration: 11.02.2017
Produced by: Parma Produkt Kft.

The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. The dose refers to the dye content (88 %, correction factor of 1.14) and corresponds to 2280 mg product/kg bw. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females/dose (3 females/step)

Control animals:

no

Details on study design:

Duration of observation period after the treatment: 14 days.

Frequency of observations:
Animals were observed individually after dosing at least once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h after the treatment and twice each
day for 14 days thereafter.

Body weight measurement:
The body weights were recorded on day 0 (just before the treatment), on day 7 and on day 15 with a precision of 1 g.

Necropsy:
At the end of the observation period all surviving rats were necropsied.

Statistics:

No statistics was used in the study.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

No lethality was noted at a single oral dose of 2000 mg/kg bw.

Clinical signs:

No treatment related symptoms were observed throughout the 14-day post-treatment period.

Body weight:

The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study.

Gross pathology:

No pathological changes were found related to the treatment with the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose.

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral LD50 was determined to be > 2000 mg dye/kg bw (corresponding to > 2280 mg test item/kg bw).

Executive summary:

An acute oral toxicity study was performed according to OECD guideline 423. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. The dose refers to the dye content (88 %, correction factor of 1.14) and corresponds to 2280 mg product/kg bw.No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met.

No lethality was noted at a single oral dose of 2000 mg/kg bw. No treatment related symptoms were observed throughout the 14-day post-treatment period. The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study. No pathological changes were found related to the treatment with the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose. The method used is not intended to allow the calculation of a precise LD50 value. The oral LD50 was determined to be > 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

OECD TG 423

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity:

An acute oral toxicity study was performed according to OECD guideline 423. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. The dose refers to the dye content (88 %, correction factor of 1.14) and corresponds to 2280 mg product/kg bw. No animal died in the first step at 2000 mg/kg bw dose level, so treatment with 2000 mg/kg bw was repeated on further three female rats. No animal died in the second step, too, so the test was finished, the stopping criteria of Annex 2d of OECD Guideline No. 423 was met. No lethality was noted at a single oral dose of 2000 mg/kg bw. No treatment related symptoms were observed throughout the 14-day post-treatment period. The mean body weight of animals treated with 2000 mg/kg bw dose corresponded to their species and age throughout the study. No pathological changes were found related to the treatment with the test item during the macroscopic examination of animals treated with 2000 mg/kg bw dose. The method used is not intended to allow the calculation of a precise LD50 value. The oral LD50 was determined to be > 2000 mg/kg bw.

Acute inhalation toxicity:

The study does not need to be conducted as exposure of humans via inhalation is not the appropriate route of exposure. Furthermore, physicochemical and toxicological properties do not suggest a potential for a significant rate of respiratory absorption.

Acute dermal toxicity:

According to REACH Annex VIII point 8.5.3 the study does not need to be conducted because 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 (e.g. skin irritation, skin sensitisation).

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),

as amended for the twelfth time in Regulation (EU) No 2019/521.