Hexamethylene diisocyanate, oligomers, reaction products with 4-Hydroxybutyl acrylate

Endpoint summary

Description of key information

Acute oral toxicity: LD50 > 2000 mg/kg bw

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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

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

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Expiration date of the lot/batch: 2019-04-20

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

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. 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 II
- 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: Februar 2017

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle:
500 mg/kg bw: 10 g/100ml
2000 mg/kg bw: 40 g/100ml
- Justification for choice of vehicle: Good homogeneity in propylene glycol

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg bw

Doses:

500, 2000 mg/kg bw

No. of animals per sex per dose:

500 mg/kg bw: 3
2000 mg/kg bw: 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
- Other examinations performed: clinical signs, body weight,organ weights

Statistics:

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

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 and the single 500 mg/kg bw test groups.

Clinical signs:

other: In all animals of both 2000 mg/kg bw test groups impaired general state and piloerection were observed from hour 3 until hour 4 or 5 after administration. In two animals of the 500 mg/kg bw test group impaired general state and piloerection were noted fr

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose of ZQ542231 after oral administration was found to be greather than 2000 mg/kg bw in rats.

Executive summary:

In an acute oral toxicity study performed according to the Acute Toxic Class Method, doses of 200 and 500 mg/kg bw of the test item ZQ542231 (preparations in propylene glycol) were administered by gavage to three test groups of three fasted Wistar rats each (2000 mg/kg bw in 6 females, 500 mg/kg bw in 3 females). No mortality occurred. Impaired general state and piloerection were present in all animals of the high dose group (2000 mg/kg bw) and in two animals of the 500 mg/kg bw dose group. The body weights of the animals increased within the normal range throughout the study period with one exception. The body weight of one animal of the first 2000 mg/kg bw test group increased during the first observation week but 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 all animals at the end of the observation period. The acute oral LD50 was calculated to be greather than 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The database is of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the results of the acute oral toxicity study and according to the EC Directive (No. 93/21/EEC) and CLP (No. 1272/2008 of 16th December 2008), the test substance does not have to be classified regarding acute oral toxicity.