Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
21 January 2015 to 11 February 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Test item: Disperse Yellow DYLA 1306

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Italia S.p.A., Calco (Lecco), Italy
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: 204 - 206 g at allocation
- Fasting period before study: Food was removed from the cages overnight prior to dosing and was made available approximately 4 hours after dosing.
- Housing: 3 animals/cage during the study; up to 5 animals/cage during acclimatisation in polisulphone solid bottomed cages measuring with nesting
material provided into suitable bedding bags
- Diet (e.g. ad libitum): ad libitum throughout the study except for the fasting period prior to dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 °C+/-2 °C
- Humidity (%): 55%+/-15%
- Air changes (per hr): approximately 15 to 20 air changes per hour
- Photoperiod (hrs dark / hrs light): artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours

IN-LIFE DATES: From: 21 January 2015 (allocation of the animals to the first group) To: 11 February 2015 (last necropsy procedure)

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: PEG 400 - water 1:1 v/v
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL. The concentration was calculated and expressed in terms of test item as supplied.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
Mortality and morbidity
Throughout the study all animals were checked twice daily.
Clinical signs
Animals were observed for clinical signs as indicated below:
– Day of dosing
Session 1: on dosing
Session 2: approximately 0.5 hour after dosing
Session 3: approximately 2 hours after dosing
Session 4: approximately 4 hours after dosing
Daily thereafter for a total of 14 days.

Body weight
All animals were weighed at allocation to the study (Day -1), on the day of dosing (Day 1) and on Days 2, 8 and 15.
Body weight change calculated for Days 2, 8 and 15 of the dosing phase was related to Day 1 of the phase.

All animals were sacrificed on Day 15 by carbon dioxide narcosis.

Necropsy was carried out on all animals (gross necropsy examination for both external and internal abnormalities, with particular attention to the
gastro-intestinal tract).

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the first group of animals initially dosed at 2000 mg/kg body weight and in the second one of 3 females dosed at the same dose level.
Clinical signs:
The only finding observed in the animals of Step I was red staining on the tail in all animals from Day 2 up to Day 15. Marked red staining of the litter was noted on Day 2 of the observation period (data not tabulated, but retained together with the study data).
All animals of the second group (Step II) showed red staining on the tail from Day 3 up to Day 15 and, a single animal, red staining in perianal region from Day 2up to Day 5. Moderate red staining of the litter was observed from Day 2 up to Day 3 of the observation period. In addition, red faeces were noted on Day 3 of
the study (data not tabulated, but retained together with the study data). These signs were no longer apparent from Day 4 up to the end of the observation
period.
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
Red stainings on tail and/or on urogenital region were observed during the external examination performed on all animals dosed at 2000 mg/kg body weight (Groups 3 and 6) at the end of the study. No internal alterations were recorded on all animals during the necropsy procedure.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
These results indicate that the test item Disperse Yellow DYLA 1306 did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg body weight. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight.
European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and
subsequent revisions) would indicate the following:
Classification: No category
Signal word: No signal word required
Hazard statement: No hazard statement required
Executive summary:

The acute toxicity of Disperse Yellow DYLA 1306 was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period.

A first group of 3 female animals was initially dosed at 2000 mg/kg bod weight (Step 1). No mortality occurred. The only finding observed was red staining on the tail in all animals from Day 2 up to Day 15. In addition, red staining of the litter was noted.

A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred. All animals showed red staining on the tail from Day 3 up to Day 15 and, a single animal, red staining in perianal region from Day 2 up to Day 5. Red faeces and red staining of the litter were also observed.

Body weight changes recorded during the study were within the expected range for this strain and age of animals.

Red staining on the tail and/or urogenital region was externally observed at necropsy examination performed at the end of the observation period. No internal abnormalities were recorded during the necropsy procedure.

These results indicate that the test item Disperse Yellow DYLA 1306 did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg body weight. The lack of mortality demonstrates the acute toxicity expected (ATE) to be greater than 2000 mg/kg body weight.

European Directives concerning the classification, packaging and labelling of dangerous substances (Council Regulation (EC) No. 1272/2008 and subsequent revisions) would indicate the following:

Classification: No category

Signal word: No signal word required

Hazard statement: No hazard statement required