Cyclohexane, 5-isocyanato-1-(isocyanatomethyl)-1,3,3-trimethyl-, homopolymer, 3,5-dimethyl-1H-pyrazole-blocked

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

February/March 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2001)

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:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 3,5-dimethyl-1H-pyrazole

EC Number:

606-423-2

Cas Number:

200295-52-9

Molecular formula:

>= C51H78N12O6 (IPDI-Isocyanurate n=3, blocked with 3,5-dimethylpyrazole)

IUPAC Name:

3-Isocyanatomethyl-3,5,5-trimethylcyclohexyl isocyanate, oligomers, reaction products with 3,5-dimethyl-1H-pyrazole

Test material form:

solid: crystalline

Specific details on test material used for the study:

- Stability under test conditions: The stability of the substance in the formulation was analytically verified for at least 2 hours. Homogeneity of the test substance in the formulation was also confirmed.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: HsdCpb:Wu
- Source: Harlan Winkelmann GmbH, 33178 Borchen, Germany
- Age at study initiation: approximately 9-12 weeks
- Weight at study initiation: 176-202 g
- Fasting period before study: Yes, food was withheld from the animals for approximately 16-24 h before administration of the test item, and they were fed again approximately 2-4 h after administration.
- Housing: The animals were group caged conventionally in polycarbonate cages on low dust wood granulate bedding.
- Diet and water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 5
- Air changes (per hr): approx. 10
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

(PEG 400)

Details on oral exposure:

Gavage, fasted animals
Administration volume: 10 mL/kg bw

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 (3 animals per step)

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Death and overt signs of toxicity were recorded repeated times on day of dosing and daily for 14 days. Bodyweights were recorded on the day of dosing and on days 7 and 14. At the end of the study all animals were subject to gross necropsy, macroscopic abnormalities were recorded, no tissues were retained.
- Necropsy of survivors performed: yes

Statistics:

The LD50 value was estimated according to OECD TG 423 (2001).

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50 cut-off

Effect level:

5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: cut-off level according to OECD TG 423, Annex 2d

Effect levels 2

Sex:

female

Dose descriptor:

discriminating dose

Effect level:

2 000 mg/kg bw

Based on:

test mat.

Mortality:

Mortality was not observed in the course of the study.

Clinical signs:

other: No clinical signs were observed.

Gross pathology:

The necropsies performed at the end of the study revealed no particular findings.

Applicant's summary and conclusion

Executive summary:

An acute oral toxicity study according to OECD TG 423 (Acute Toxic Class Method) was conducted on 6 female rats (3 per step), receiving each a single dose of 2000 mg/kg of the substance formulated in polyethylene glycol. No mortalities, no clinical signs, no effects on body weight or body weight gain and no particular findings at necropsy were observed. Therefore, according to the flow chart of the OECD TG 423, Annex 2d, the LD50 cut off for the substance is 5000 mg/kg bw, and the discriminating dose is 2000 mg/kg.