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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

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:

SOURCE OF TEST MATERIAL
- Expiration date of the lot/batch: 2019-05-23

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

Test animals

Species:

rat

Strain:

Wistar

Remarks:

Crl:WI(Han) SPF

Sex:

male/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: males approx. 8 weeks, females approx. 12 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: April 2017

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

propylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: about 40cm² (corresponds to at least 10% of the body surface
- % coverage: semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Rinsing the application site with warm water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10ml/kg bw
- Concentration (if solution): 20g/100ml
- Constant volume or concentration used: yes

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

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: Scoring of akin findings: individual readings 30-60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter and on the last day of observation.
- Assessment of skin reactions: The evaluation of skin reactions was performed according to Draize, J. H. "Dermal toxicity." Appraisal of the safety of chemicals in foods, drugs and cosmetics (1959): 46-59.

Statistics:

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

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortatlity occurred.

Clinical signs:

other: No systemic clinical signs were observed during clinical examinateion. No local effects were observed in males. Moderate to severe erythema (grade 3) and very slight edema (grade 1) was noticed in three out of five female animals on study day 14.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals (5 males and 5 females) examined on the last day of observation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study the median lethal dose (LD50) of the test item after dermal application was found to be greater than 2000 mg/kg bw in male and female rats.

Executive summary:

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.