Hexamethylene diisocyanate, oligomers, reaction products with Bis-(Trimethoxysilylpropyl)amine

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:

2018

Report date:

2018

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:

1-{6-[3,5-bis(6-isocyanatohexyl)-2,4,6-trioxo-1,3,5-triazinan-1-yl]hexyl}-3,3-bis[3-(trimethoxysilyl)propyl]urea

EC Number:

918-105-3

IUPAC Name:

1-{6-[3,5-bis(6-isocyanatohexyl)-2,4,6-trioxo-1,3,5-triazinan-1-yl]hexyl}-3,3-bis[3-(trimethoxysilyl)propyl]urea

Test material form:

liquid: viscous

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

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Wiga GmbH, Germany
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approx. 10weeks
- Weight at study initiation: animals of comparable weight
- Fasting period before study: at least 16 h before administration
- Housing: Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany, 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): 12 /12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1.75 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 (first administration group, 15 days (second administration group)
- Frequency of observations and weighing: Individual body weights 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. A check for 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 checked 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 test groups.

Clinical signs:

other: In the first test group impaired general state and piloerection were observed in all animals from hour 2 or 3 until hour 5 or study day 1. In the second test group impaired general state and piloerection were observed in all animals from hour 4 until hour

Gross pathology:

There were no macroscopic pathological findings in any animal sacrificed at the end of the observation period.

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, a dose of 2000 mg/kg bw of the undiluted test item were administered by gavage to two test groups of three fasted Wistar rats each (2000 mg/kg bw in 6 females). No mortality occurred. Impaired general state and piloerection was noted in all animals. The body weights of the animals increased within the normal range throughout the study period with two exceptions. The body weights of two animals of the second administration group increased normally during the first observation week but nearly stagnated during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth. There were no macroscopic pathological findings in any animal sacrificed at the end of observation period (6 females).

 The acute oral LD₅₀was calculated to be higher than 2000 mg/kg bw.