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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12th February 2018 to 28th February 2018
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction product of 1,5-naphthylene diisocyanate (221-641-4) and cyclohexylamine (203-629-0)
Molecular formula:
C24H32N4O2
IUPAC Name:
Reaction product of 1,5-naphthylene diisocyanate (221-641-4) and cyclohexylamine (203-629-0)
Test material form:
solid

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Envigo RMS (UK) Limited, Oxon, UK
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 178 - 217 g
- Fasting period before study: Overnight fast immediately before dosing
- Housing: The animals were housed in groups of up to four in suspended solid-floor polypropylene cages furnished with woodflakes
- Water (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to mains drinking water
- Diet (e.g. ad libitum): With the exception of an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing, free access to food 2014C Teklad Global Rodent diet supplied by Envigo RMS (UK) Limited, Oxon
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): At least 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: Hexane
Details on oral exposure:
VEHICLE
- Concentration in vehicle: Calculated per individual so that each test animal was dosed at 2000 mg/kg
- Amount of vehicle (if gavage): Dose volume: 10 mL/kg
- Justification for choice of vehicle: Hexane was used because the test item did not dissolve/suspend in distilled water, arachis oil or dimethylsulfoxide
- Lot/batch no. (if required): Not reported
- Purity: Not reported

MAXIMUM DOSE VOLUME APPLIED: 200 mg/mL

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Using available information on the toxicity of the test item, 2000 mg/kg was chosen as the starting dose.
Doses:
2000 mg/kg
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:
A single female rat was dosed at 2000 mg/kg initially. In the absence of toxicity at the dose level of 2000 mg/kg, an additional group of 4 animals were dosed at 2000 mg/kg
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities during the study.
Clinical signs:
Tiptoe gait and/or hunched posture were noted in one animal up to one day after dosing. The remaining four animals appeared normal throughout the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight, the sole concentration tested. The test item is not classified based on the UN GHS criteria.

Executive summary:

The acute oral toxicity of the test item was determined in an OECD 420 and EU Method B1 bis Acute Toxicity (Oral) guideline study as a limit test. The test item was tested at 2000 mg/kg as a suspension in hexane, prepared a maximum of 2 hours prior to study initiation, orally by gavage using a metal canula. Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily during normal working days, and once daily at weekends and public holidays. Additional the animal body weights were determined on Days 0, 7 and 14.

In a preliminary study, one adult female Wistar rat was dosed with 2000 mg/kg test item, and no mortalities, effects on body weight or adverse findings during necropsy were observed, therefore four further female Wistar rats were dosed with 2000 mg/kg test item. No deaths or signs of systematic toxicity or adverse findings during necropsy were observed during the study and the test animals achieved the expected weight gains during the study. Tiptoe gait and/or hunched posture was noted in one animal up to one day after dosing, but appeared normal for the remainder of the test. The remaining four animals appeared normal throughout the observation period. The acute oral median lethal dose (LD50) of the test item in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight, the sole concentration tested. The test item is not classified based on the UN GHS criteria.

The study is a GLP compliant guideline experimental study and is acceptable without restrictions for assessment of this endpoint.