N,N”-hexane-1,6-diylbis(N’-alkylaryl)urea

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

31 July - 22 Aug 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP-Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Details on test material:

- Name of test material (as cited in study report): trade name given
- Substance type: white powder
- Analytical purity: 99.5%
- Lot/batch No.: 1592ZG-076
- Expiration date of the lot/batch: Aug 2015
- Storage condition of test material: at room temperature
- Other: pH: 6.4-6.3 (1% in water)

Test animals

Species:

rat

Strain:

other: Crl:WI (Han) (outbred, SPF-Quality)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approx. 8-10 weeks
- Weight at study initiation: 159-196 g
- Fasting period before study: Animals were fasted overnight prior to administration and until approx. 1 hour and 10 minutes (first group at 2000 mg/kg bw) or approx. 30 minutes (second group at 2000 mg/kg bw) after the second administration of the test substance. Water was available ad libitum.
- Housing: groups of 3 animals in Makrolon cages (MIV type; height 18 cm), sterilized sawdust was used as bedding material, paper as cage-enrichment
- Diet: SM R/M-Z (SSNIFF Spezialdiäten GmbH, Soest, Germany), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24
- Humidity (%): 40-70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 31 July 2014 To: 22 Aug 2014

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

FREQUENCY: Due to a maximum concentration of 10% test substance formulations two dosages within 24 hours on Day 1 were applied. The first on t=0 hours and the second on t=3 hours.

Doses:

2000 mg/kg bw (by administration of two times 1000 mg/kg bw)

No. of animals per sex per dose:

6 (3 per step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at periodic intervals on the day of dosing (Day 1) and once daily thereafter until Day 15. Individual body weights were determined on Day 1 before administration of the test substance and thereafter in weekly intervals. Observations on mortality were made twice daily.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off 5000 mg/kg bw according to OECD 423

Mortality:

No mortality occurred during the study period.

Clinical signs:

Hunched posture and piloerection were noted for all animals between Days 1 and 3. Uncoordinated movements were noted for one animal on Day 1.

Body weight:

All animals gained the expected body weight over the study period.

Gross pathology:

No abnormalities were noted at necropsy of animals.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

CLP: not classified
DSD: not classified