3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, 2-Hydroxy-1(2)- methylethyl carbamate blocked

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

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:

2-(carbamoyloxy)propyl N-[(3-{[3,5-bis({5-[({[2-(carbamoyloxy)propoxy]carbonyl}amino)methyl]-1,3,3-trimethylcyclohexyl}methyl)-2,4,6-trioxo-1,3,5-triazinan-1-yl]methyl}-3,5,5-trimethylcyclohexyl)methyl]carbamate

EC Number:

921-910-2

IUPAC Name:

2-(carbamoyloxy)propyl N-[(3-{[3,5-bis({5-[({[2-(carbamoyloxy)propoxy]carbonyl}amino)methyl]-1,3,3-trimethylcyclohexyl}methyl)-2,4,6-trioxo-1,3,5-triazinan-1-yl]methyl}-3,5,5-trimethylcyclohexyl)methyl]carbamate

Test material form:

solid

Details on test material:

- Analytical purity: 83.9 g/100g
- Composition of test material, percentage of components: 0.2g/100g water, 13.4g/100g n-butyl acetate, 2.5g/100g 1,2-propanediol, monocarbamate
- Lot/batch No.: 389-48
- Expiration date of the lot/batch: 2019-05-23

Specific details on test material used for the study:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RccHan:WIST and Crl:WI(Han) SPF

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Envigo RMS GmbH, Germany and Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10 weeks
- Weight at study initiation: animals were of comparable weight
- Fasting period before study: at least 16 hours before administration, water was available ad libitum
- Housing: single housing, Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1 (P); SDS Special Diets Services; ad libitum
- Water (e.g. ad libitum):Tap water ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 30-70
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12h / 12h

IN-LIFE DATES: April 2017

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 2000 mg/kg bw: 20 g/100ml
- Justification for choice of vehicle: Good homogeneity in propylene glycol

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Individual body weight were determined shortly before administration, weekly thereafter and on the last day of observation.
Clinical signs for each animal were recorded several times on the day of administration and at least once during each workday thereafter.
Mortality: A check for any dead or moribund animals was made at least once each workday.
- Necropsy of survivors performed: yes

Statistics:

Calculations were performed using Microsoft Excel 2010 and cheked with a calculator.

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 in both 2000 mg/kg bw test groups.

Clinical signs:

other: In all animals of the first 2000 mg/kg bw test group impaired general state and piloerection was observed from hour 1 until hour 5 after administration. In all animals dyspnoea was seen at hour 2 and persisted in two of these animals until hour 4 or 5. St

Gross pathology:

There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period with one exception in the second test group. In one animal a conglomerate of test item and stomach contents was found in the stomach during necropsy.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of the test item after oral administration was found to be greater than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, 2000 mg/kg bw of the test item were administered by gavage to two test groups of three fasted Wistar rats each (6 females).

No mortality occurred. Impaired general state, dyspnoea and piloerection were noted in all animals and cowering position as well as staggering in 3 of 6 animals within the first 5 hours after administration.

The body weights of all animals increased within the normal range throughout the study period. There were no macroscopic pathological findings in the animals sacrificed at the end of the observation period with one exception in the second 2000 mg/kg bw test group. In this animal a conglomerate of test item and stomach contents was found in the stomach during necropsy.

The acute oral LD50 was calculated to be higher than 2000 mg/kg bw.