4,4'-isopropylidenediphenyl dicyanate

Endpoint summary

Description of key information

Acute oral toxicity

The study was performed according to the acute toxic class method (OECD 423 and EC B.1.Tris) in Wistar rats. Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As only one animal was found dead, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required according to the testing guidelines.One animal was found dead after treatment at a dose level of 2000 mg/kg bw. Clinical observations included decreased activity (6/6), piloerection (6/6), hunched back (5/6) and prone position (3/6) and were observed on the day of treatment. The five surviving animals became symptom-free from the day after treatment. No effects were observed on body weights or body weight gains in any surviving animal during the study. Necropsy showed multifocal dark/red discoloration of the stomach glandular mucosa in the rat that died after treatment. This was considered to be test item-related. In addition, enlargement of the dark/red discoloured lungs, white foamy material in the trachea and light/red liquid material at the perinasal were also observed in this animal at necropsy. Following a 14 day observation period, no test item-related gross changes were recorded in the surviving rats

Under the conditions of this study, the acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female Wistar rats. According the GHS criteria, LZ 514 can be classified as "Category 5" for acute oral exposure.

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:

January - April 2016

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Test Substance Name: LZ 514
- Source: Lonza Ltd, Visp/Switzerland
- Lot/batch No. of test material: 5011
- Expiration date of the lot/batch: 2nd December 2017
- Manufacture date: 3rd December 2015

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage conditions: Controlled room temperature (15-25 ºC, below 70 RH%), protected from light and humidity.
- Stability under test conditions: stable
- Safety precautions: Routine safety precautions (lab coat, gloves, safety glasses, face mask) for unknown materials were applied to assure personnel health and safety.

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Females (nulliparous and non-pregnant): yes
- Age at study initiation: young healthy adult rats, 11 weeks old
- Weight at study initiation: 242 – 253 g
- Fasting period before study: the night before treatment, animals were fasted
- Housing: 3 animals / cage
- Water (e.g. ad libitum): tap water from the municipal supply
- Acclimation period: 26-27 days
- Diet (e.g. ad libitum): ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" from ssniff Spezialdiäten GmbH, D-59494 Soest, Germany

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0 - 24.8 °C
- Humidity (%): 31 - 66%
- Air changes (per hr): 15-20 air exchanges/hour
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Details on oral exposure:

The test item was freshly formulated at a concentration of 200 mg/mL in the vehicle at the test lab on the day of administration. The formulation container was stirred continuously up to finishing the treatment.

Doses:

Single dose of 2000 mg/kg bw

No. of animals per sex per dose:

Initially, three female animals were treated with 2000 mg/kg bw of the test item. One animal died, therefore further 3 animals were treated at the dose level of 2000 mg/kg bw. As no mortality was observed in this second dose group, further testing was not required according to the test guidelines.

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: clinical observations were performed on all animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Body weights were recorded on the day before treatment (day -1), on the day of the treatment (day 0) and weekly thereafter, where possible. Terminal body weight of the animal found dead was recorded.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

One animal was found dead after treatment at a dose level of 2000 mg/kg bw.

Clinical signs:

other: Decreased activity (6/6), piloerection (6/6), hunched back (5/6) and prone position (3/6) were observed in the animals on the day of treatment. The five surviving animals became symptom-free from the day after treatment.

Gross pathology:

Multifocal dark/red discoloration of the stomach glandular mucosa was found in the rat that died after treatment. This was considered to be test item-related. In addition, enlargement of the dark/red discoloured lungs, white foamy material in the trachea and light/red liquid material at the perinasal were also observed in this animal at necropsy. Following a 14 day observation period, no test item-related gross changes were recorded in the surviving rats.

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

Under the conditions of this study, the acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female CRL:(WI) rats. According the GHS criteria, LZ 514 can be classified as "Category 5" for acute oral exposure.

Executive summary:

The study was performed according to the acute toxic class method (OECD 423 and EC B.1.Tris) in Wistar rats. Initially, three females (Group 1) were treated at a dose level of 2000 mg/kg bw. As only one animal was found dead, a confirmatory group (Group 2) was treated at the same dose level. No mortality was observed in the confirmatory group; therefore no further testing was required according to the testing guidelines.One animal was found dead after treatment at a dose level of 2000 mg/kg bw. Clinical observations included decreased activity (6/6), piloerection (6/6), hunched back (5/6) and prone position (3/6) and were observed on the day of treatment. The five surviving animals became symptom-free from the day after treatment. No effects were observed on body weights or body weight gains in any surviving animal during the study. Necropsy showed multifocal dark/red discoloration of the stomach glandular mucosa in the rat that died after treatment. This was considered to be test item-related. In addition, enlargement of the dark/red discoloured lungs, white foamy material in the trachea and light/red liquid material at the perinasal were also observed in this animal at necropsy. Following a 14 day observation period, no test item-related gross changes were recorded in the surviving rats

Under the conditions of this study, the acute oral LD50 value of the test item was found to be above 2000 mg/kg bw in female Wistar rats. According the GHS criteria, LZ 514 can be classified as "Category 5" for acute oral exposure.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Guideline study; Klimisch 1

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

According to the GHS criteria, the test item can be classified as "Category 5" for acute oral exposure.