Hexamethylene diisocyanate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

before July 1970

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1970

Report date:

1970

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

no data on body weights or necropsy findings

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexamethylene diisocyanate

EC Number:

212-485-8

EC Name:

Hexamethylene diisocyanate

Cas Number:

822-06-0

Molecular formula:

C8H12N2O2

IUPAC Name:

1,6-diisocyanatohexane

Constituent 2

Reference substance name:

Desmodur H

IUPAC Name:

Desmodur H

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: breeder Winkelmann (Kirchborchen, Germany)
- Age at study initiation: no data
- Weight at study initiation: 160-200 g
- Housing: no data
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21+/- 2
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 /12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: oil, not specified

Details on oral exposure:

application volume: 5 ml/kg bw

Doses:

0.1, 0.25, 0.5, 0.75, 1.0, 1.5, and 2.0 mL/kg bw corresponding to 105, 263, 525, 788, 1050, 1575, and 2100 mg/kg bw (density 1.05 g/cm³ at 25 °C)

No. of animals per sex per dose:

15

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: daily
- Necropsy of survivors performed: no
- Other examinations performed: clinical signs

Statistics:

LD50 values were calculated according to the method of Litchfield and Wilcoxon (J. Pharmacol. exper. Therap. 96: 99, 1949).

Results and discussion

Effect levels

Sex:

male

Dose descriptor:

LD50

Effect level:

959 mg/kg bw

95% CL:

>= 837 - <= 1 103

Remarks on result:

other: corresponding to 0.913 mL/kg

Mortality:

Minumum lethal dose: 788 mg/kg bw
Mortalities at dose levels: 0/15 at 105 mg/kg, 0/15 at 263 mg/g, 0/15 at 525 mg/kg, 5/15 at 788 mg/kg, 11/15 at 1050 mg/kg, 14/15 at 1575 mg/kg, 15/15 at 2100 mg/kg. All deaths occurred within the first day after treatment.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

no data

Gross pathology:

no data

Any other information on results incl. tables

Table 1: Toxicological results after single oral application of HDI to male rats

Sex	Dose (mg/kg bw)	Toxicological results	Onset and duration of signs	Onset of mortality
male	105	0 / 0 / 15	---	---
	263	0 / 15 / 15	2h - 3d	---
	525	0 / 15 / 15	1h - 7d	---
	788	5 / 15 / 15	50m - 7d	1d
	1050	11 / 15 / 15	40m - 7d	1d
	1575	14 / 15 / 15	35m	1d
	2100	15 / 15 / 15	30m	1d

Toxicological results:

number of dead animals / number of animals with signs after treatment / number of animals treated

Applicant's summary and conclusion

Executive summary:

An acute oral toxicity study in male Wistar rats is available for the substance. In that study, which was conducted prior to GLP and OECD guidelines, 15 rats per dose group were administered by gavage (administration volume 5 mL/kg) with substance formulations in oil at 105, 263, 525, 788, 1050, 1575, and 2100 mg/kg bw. During a 14 -day post-dosing period animals were at least daily observed for clinical signs and mortalities. No body weights were reported and no necropsy was conducted. LD50 values were calculated according to the method of Litchfield and Wilcoxon.

The oral LD50 in this study was 959 mg/kg for male Wistar rats. At 263 mg/kg and above all animals showed a reduced general condition and a mild sedation. The NOEL with regard to mortality and clinical signs was 105 mg/kg.