Reaction mass of bis[4-(vinyloxy)butyl] hexane-1,6-diylbiscarbamate and 9,18-dioxo-3,8,19-trioxa-10,17-diazapentacos-1-en-25-yl [6-({[4-(vinyloxy)butoxy]carbonyl}amino)hexyl]carbamate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

02 July, 2013 - 18 July, 2013

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2013

Report date:

2013

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2001)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

(2008)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

(2002)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nohsan, Notification No 8147, April 2011, including the most recent partial revisions.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

420-990-1

EC Name:

-

Cas Number:

146421-65-0

Molecular formula:

C20H36N2O6

IUPAC Name:

4-(ethenyloxy)butyl N-[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamate

Constituent 2

Reference substance name:

4-(ethenyloxy)butyl N-{6-[({[6-({[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamoyl}oxy)hexyl]oxy}carbonyl)amino]hexyl}carbamate

Cas Number:

1516571-16-6

Molecular formula:

C34H62N4O10

IUPAC Name:

4-(ethenyloxy)butyl N-{6-[({[6-({[6-({[4-(ethenyloxy)butoxy]carbonyl}amino)hexyl]carbamoyl}oxy)hexyl]oxy}carbonyl)amino]hexyl}carbamate

Details on test material:

- Name of test material (as cited on the label): URACROSS ZW7672P, Product ID 021116/000
- Storage condition of test material: At room temperature in the dark
- Stability under storage conditions: Stable

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: 142 - 169 g
- Fasting period before study: overnight prior to dosing and until 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

GAVAGE METHOD: plastic feeding tubes.

Frequency: single dosage, on Day 1.

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of the vehicle. No correction was made for purity of the test substance.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily.
Body weights: Days 1 (pre-administration), 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: At the end of the observation period, all animals were sacrificed by oxygen/carbon dioxide procedure and subjected to necropsy.
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

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.

Clinical signs:

other: Hunched posture was seen only on the day of treatment for three of the six animals.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD 423 test guideline and GLP principles, an LD50 >2000 mg/kg bw was determined.

Executive summary:

The test substance was assessed for toxicity in an acute oral toxicity study with female Wistar rats, performed according to OECD 423 test guideline and GLP principles. No mortality occurred. Hunched posture was seen only on the day of treatment for three of the six animals. No abnormalities were found at macroscopic post mortem examination of the animals. Based on the results, the oral LD50 value of URACROSS ZW7672P, Product ID 021116/000 in Wistar rats was established to exceed 2000 mg/kg body weight.

According to Regulation (EC) No 1272/2008, URACROSS ZW7672P, Product ID 021116/000 does not have to be classified for acute oral toxicity.