Reaction products of cyclohexylamine and 4-alkylaniline and 1,1'-methanediylbis(4-isocyanatobenzene)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From 1991-07-26 to 1991-08-09

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

GLP study in accordance with recognised test guideline but: Lot/batch No.and Expiration date were not stated NOTE: study deemed acceptable because spectral data are available, covering approximately before and after the test period - see section 1.4 Analytical Information.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Specific details on test material used for the study:

- Substance type: Organic
- Physical state: fine off-white powder
- Analytical purity: Approximately 100%
- Storage condition of test material: at ambient temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (U.K.) Limited, Margate, Kent, England.
- Age at study initiation: approximately 5 weeks old
- Weight at study initiation: 148-161g (male); 131-144g (female)
- Fasting period before study: 18 hours
- Housing: stainless steel grid cages measuring 54 x 33 x 20 cm (Steven Clarke Fabrications Limited, Alva, Clackmannanshire, Scotland). Five animals of the same sex were accommodated in each cage. The cages were suspended in mobile stainless steel racks.
- Diet (e.g. ad libitum): commercially-available complete pelleted rodent diet (Laboratory Animal Diet No.1, from Biosure, Manea, Cambridgeshire, England) was fed without restriction
- Water: free access to tap water supplied in a single bottle per cage and re-filled as required. The water was taken from the public supply; in England the supply and quality of this water is governed by Department of the Environment regulations.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C (range 18°-25°C)
- Humidity (%): 55% R.H. (range 40%-70% R.H.)
- Air changes (per hr): 15 complete air changes per hour without recirculation
- Photoperiod (hrs dark / hrs light): lighting cycle of 12 hours of artificial light per day


IN-LIFE DATES: From: 26 July 1991 To: 9 August 1991

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5% w/v methylcellulose in purified water (obtained through the reverse osmosis of tap water).

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bodyweight, at a volume-dosage of 20 mL/kg

DOSAGE PREPARATION: The test material was prepared at the appropriate concentration in 0.5% w/v methylcellulose in purified water (obtained through the reverse osmosis of tap water). The dosage was calculated and expressed gravimetrically in terms of the material as received. A fresh formulation of the test material was prepared on the morning of administration and any surplus remaining after dosing was destroyed on the same day.

Doses:

2000 mg/kg bodyweight

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Three separate inspections were made during the first hour after dosing and two further inspections during the remainder of Day 1. From Day 2 onwards, the animals were inspected twice daily (morning and afternoon).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: The type, time of onset and duration of reactions to treatment were recorded. The bodyweight of each animal was recorded on the day before dosing and on Days 1, 8 and 15.

Results and discussion

Preliminary study:

A preliminary study was carried out using one group of one male and one female rat given a single oral administration of test item at a dosage of 800 mg/kg bodyweight, at a volume-dosage of 20 ml/kg in 0.5% w/v aqueous methylcellulose. There was no death and no sign of reaction to treatment.

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No death

Clinical signs:

other: No signs of reaction to treatment

Gross pathology:

Necropsy revealed no significant macroscopic lesion

Applicant's summary and conclusion

Interpretation of results:

other: low oral toxicity

Conclusions:

Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mk/kg. Accordingly, the test item was assigned to the class 'low oral toxicity'.

Executive summary:

The acute oral toxicity of test item, was investigated in a group of five male and five female CD rats at a dosage of 2000 mg/kg based on OECD 401. The animals were starved overnight prior to dosing. The test material was administered at a volume-dosage of 20 ml/kg in 0.5% w/v aqueous methylcellulose. Mortality and signs of reaction to treatment were recorded during a subsequent 14-day observation period. The animals were killed on the following day and subjected to necropsy.

There was no death and no sign of reaction to treatment. All animals achieved expected bodyweight gains and necropsy revealed no significant macroscopic lesion. Under the conditions of this study, the acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg. Accordingly, the test item was assigned to the class 'low oral toxicity'.