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

Endpoint summary

Description of key information

Oral:

The acute oral toxicity of test item was investigated according to OECD 401.

There was no death and no sign of reaction to treatment. All animals achieved expected bodyweight gains and necropsy revealed no significant macroscopic lesion. The acute oral median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.

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:

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.: not stated Expiration date of the lot/batch: not stated NOTE: study deemed acceptable because spectral data for test item are available, covering approximately before and after the test period - see section 1.4 Analytical Information.

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1997

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Specific details on test material used for the study:

Purity: Ca. 100%

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Limited, Margate, Kent, England
- Age at study initiation: Approximately 5 weeks
- Weight at study initiation: 138 - 155 g for males and 127 - 134 g for females
- Fasting period before study: 18 hours
- Housing:The animals were housed in stainless steel grid cages measuring 54 x 33 x 20 cm (Steven Clarke Fabrications Limited, Alva, Clackmannanshire, Scotland).
- Diet (e.g. ad libitum): Laboratory Animal Diet No. 1 from Biosure, Manea, Cambridgeshire, England, fed ad libitum.
- Water (e.g. ad libitum): Tap water ad libitum.
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): Target 21ºC, actual range 18º - 25ºC
- Humidity (%): Target 55% RH, actual range 40% - 70% RH
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12


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

Route of administration:

oral: gavage

Vehicle:

other: 0.5% (w/v) Aqueous Methylcellulose.

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 0.5% w/v aqueous methylcellulose
- Amount of vehicle (if gavage): 20 mL / kg

MAXIMUM DOSE VOLUME APPLIED: 2000 mg / kg

DOSAGE PREPARATION (if unusual): 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.


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: 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.
On the basis of this result, the main study was carried out using a single group of five male and five female rats given a single oral administration of test item at the maximum practicable dosage of 2000 mg/kg (Regulatory limit test), at a volume-dosage of 20 mL/kg. Since no rat died as a result of treatment the low toxicity of test item was demonstrated and no further groups of animals were employed.

Doses:

2000 mg / kg

No. of animals per sex per dose:

Five male and five female

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing:Twice daily for 15 days, with weighing on day 1, 8, and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, gastr-intestinal tract.

Statistics:

Not applicable

Preliminary study:

A preliminary study was undertaken by administering one female rat and one male rat with a single oral dose of 800 mg / kg. There was no death and no sign of reaction to treatment.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: None

Gross pathology:

No significant pathological findings

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 mg / kg.

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 according to 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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

2 (reliable with restrictions)

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Oral LD50: >2000 mg/kg body weight

Therefore in accordance with Regulation (EC) No. 1272/2008 (amended by 286/2011) Table 3.1.1 , this substance should not be classified for acute toxicity.

Specific target organ toxicity-single exposure:

Oral:

Death: No death at 2000 mg/kg (0/10).

Clinical observations: No signs of reaction to treatment

Body weight: All animals achieved expected bodyweight gains

Macroscopic Findings: Necropsy revealed no significant macroscopic lesion 

Therefore in accordance with Regulation (EC) No. 1272/2008 Table 3.8.1 and 3.8.2, this substance should not be classified for this endpoint.