Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
09 April 2018 - 01 May 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2018

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
December 2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
December 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF Guidelines
Version / remarks:
2000, including the most recent revisions.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
d.d. 22 January 2018
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Test material form:
solid: particulate/powder
Details on test material:
- Appearance: Pink powder
- Storage conditions: At room temperature
Specific details on test material used for the study:
Composition correction factor: 1.074

Test animals

Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8-9 weeks old)
- Nulliparous and non-pregnant: Yes
- Weight at study initiation: 143 to 175 g.
- Fasting period before study: yes
- Housing: Group housing of 3 animals per cage in labeled polycarbonate Makrolon cages (type: MIV) containing sterilized sawdust as bedding material.
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany), except overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

The feed was analyzed by the supplier for nutritional components and environmental contaminants, there were no known contaminants in the feed that would interfere with the objectives of the study.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (daily mean; set conditions: 18-24)
- Humidity (%): 43 - 51%
- Air changes (per hr): Ten or more
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10 April 2018 to 01 May 2018

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1% (aqueous solution)
Details on oral exposure:
GAVAGE METHOD: syringe with a plastic gavage cannula

Frequency: single dosage, on day 1.

MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg body weight (10 mL/kg body weight)

- Rationale for the selection of the starting dose: maximum recommended dose according to OECD 423.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 (2 groups of three females in a stepwise manner).
Control animals:
no
Details on study design:
The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg bodyweight. Based on the results, one additional group was dosed at 2000 mg/kg bodyweight.

Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter.

Mortality/Viability: Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day.

Body weights: Animals were weighed individually on day 1 (predose), 8 and 15.

Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15.

- Necropsy of survivors performed: yes
- Other examinations performed: none.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture and/or piloerection were noted for the animals on days 1 and/or 2.
Pink discoloration (faeces, tail, back and/or general) was noted for the animals between days 3 and 12. This was considered to be caused by the staining properties of the test item and therefore not toxicologically relevant.
Body weight:
No abnormalities were noted. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Any other information on results incl. tables

According to the OECD 423 test guideline, the LD50 cut-off value was considered to be 5000 mg/kg body weight.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity test, performed according to OECD/EC guidelines and GLP principles, the oral LD50 of C.I. Pigment Red 81:2 was found to be > 2000 mg/kg bodyweight. Based on the results, C.I. Pigment Red 81:2 does not need to be classified according to GHS and CLP criteria.