Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 August 2016 - 13 September 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report Date:
2016

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
yes
Remarks:
The first dosing group received a dose of 1975 mg/kg bw instead of 2000 mg/kg bw. Since the deviation was only very slight, and as the second group was correctly dosed with 2000 mg/kg bw, it did not have any impact on the conclusion of the study.
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
May 2008, including the most recent amendments
Deviations:
yes
Remarks:
The first dosing group received a dose of 1975 mg/kg bw instead of 2000 mg/kg bw. Since the deviation was only very slight, and as the second group was correctly dosed with 2000 mg/kg bw, it did not have any impact on the conclusion of the study.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
2002
Deviations:
yes
Remarks:
The first dosing group received a dose of 1975 mg/kg bw instead of 2000 mg/kg bw. Since the deviation was only very slight, and as the second group was correctly dosed with 2000 mg/kg bw, it did not have any impact on the conclusion of the study.
Qualifier:
according to
Guideline:
other: JMAFF Guidelines
Version / remarks:
2000, including the most recent partial revisions
Deviations:
yes
Remarks:
The first dosing group received a dose of 1975 mg/kg bw instead of 2000 mg/kg bw. Since the deviation was only very slight, and as the second group was correctly dosed with 2000 mg/kg bw, it did not have any impact on the conclusion of the study.
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid
Details on test material:
- Appearance: Brown coloured, brittle solid
- Storage condition of test material: At room temperature
- Chemical name: Zinc modified rosinate, hydrogenated zinc rosinate
- CAS No.: 68425-02-5
Specific details on test material used for the study:
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Stability for at least 6 hours at room temperature and 8 days in the refrigerator is confirmed over the concentration range 1 to 200 mg/mL, Project 512287

Test animals

Species:
rat
Strain:
Wistar
Remarks:
Crl:WI
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: ca. 8-9 weeks
- Weight at study initiation: 146-181 g
- Fasting period before study: yes, overnight prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages (MIV type; height 18 cm) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) and paper as cage-enrichment (Enviro-dri, Wm. Lillico & Son (Wonham Mill Ltd), Surrey, United Kingdom)
- Diet (e.g. ad libitum): free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water (e.g. ad libitum): free access to tap water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.8-22.5
- Humidity (%): 50-72
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 23-08-2016 To: 13-09-2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
propylene glycol
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg bw
- Justification for choice of vehicle: The vehicle was selected based on trial preparations performed at Charles River Den Bosch and on test item data supplied by the Sponsor. There was no information available regarding the solubility in vehicle.

MAXIMUM DOSE VOLUME APPLIED:
10 mL/kg bw

DOSAGE PREPARATION (if unusual):
The preparations (w/w) were kept at room temperature and were dosed within 4 hours after adding the vehicle to the test item. Homogeneity was assessed by visual inspection of the solutions and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies. Adjustment was made for specific gravity of the vehicle (1.036). No correction was made for purity of the test item.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: the maximal limit dose as required by the guideline
Doses:
1975 and 2000 mg/kg bw
No. of animals per sex per dose:
3 females/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: twice daily for mortality; clinical signs were checked at periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15. The signs were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1).
Body weights were determined on Days 1 (pre-administration), 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weights
Statistics:
Not performed (the method is not intended to derive an LD50)

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:
Uncoordinated movements, piloerection and/or hunched posture were noted for all animals on Day 1.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
The body weight of one female was found to be unrealistically low on review of the data, as a result of human error. As the body weight of the other five animals was as expected, this result was not considered to affect the findings of the study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:
other: Not classified under Regulation 1272/2008/EC
Conclusions:
In a GLP-compliant guideline acute oral toxicity study with rats, the LD50 was found to exceed 2000 mg/kg bw. Based on this no classification of the test substance under Regulation 1272/2008/EC is warranted.
Executive summary:

In a GLP-compliant OECD guildeline 423 study, the test substance dissolved in propylene glycol was administered by oral gavage to two groups of 3 female rats at dose levels of 1975 mg/kg bw (deviation from the study protocol) and 2000 mg/kg bw. No mortality occurred. Uncoordinated movements, piloerection and/or hunched posture were noted for all animals on Day 1. The mean 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. No abnormalities were found at macroscopic post mortem examination of the animals. Based on this, the acute oral LD50 was considered to be above 2000 mg/kg bw. Based on these results, the substance is not considered to be acutely toxic under conditions of the study, and no classification is warranted under Regulation 1272/2008/EC.