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

Endpoint summary

Description of key information

- Acute oral toxicity, rat: LD50 > 2000 mg/kg bw

- Acute dermal toxicity, rat: 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:

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

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

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.

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.

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The whole database is of high quality.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

The whole database is of high quality.

Additional information

Acute oral toxicity:

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.

Acute dermal toxicity:

In an acute dermal toxicity study (Limit Test), young adult Wistar rats (5 males and 5 females) were dermally exposed to a single dose of 2000 mg/kg bw of the test item. The clipped application site (dorsal and dorso-lateral parts of the trunk, comprising at least 10% of the total body surface) was covered by semi-occlusive dressing during the 24-hour exposure period. The animals were observed for 14 days.

No mortality occurred. Neither signs of systemic toxicity nor local skin effects were observed in any male animal. No signs of systemic toxicity were observed in the female animals.

Moderate to severe erythema (grade 3) and very slight edema was noted in three females on study day 14. The body weight of all male and three female animals increased within the normal range throughout the study period. The body weight in two female animals slightly decreased or stagnated during the first week, probably due to the bandage procedure, but increased within the normal range during the second week.

No macroscopic pathologic abnormalities were noted in the animals examined at the end of the study (5 males and 5 females).

Accordingly, the acute dermal median lethal dose (LD50) was determined to be higher than 2000 mg/kg bw.

Justification for classification or non-classification

Based on the results of the acute oral and dermal toxicity studies 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 toxicity.