Condensation products of m-phenylenebis(methylamine) with condensation products of 4-methyl-m-phenylene diisocyanate with alcohols, C10-14 (even numbered) and condensation products of 4-methyl-m-phenylene diisocyanate with butyltriglycol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: see 'Remark'

Remarks:

The study was conducted according to internationally accepted technical guidelines and in compliance with GLP in a contract research organization. The study is scientifically valid and the report is fully adequate for assessment, despite some minor restrictions (e.g. due to limited reporting).

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

of 1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, Division of Pharmacology, FDA, 1959

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Remarks:

Certified by BAM according to DIN EN 45001.

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Wistar rats, strain: Winkelmann, Paderborn (SPF-Quality) with appropriate range of bodyweight at study start.
- Bodyweight at study start (day of dosing): Males: minimum 214 g, maximum 231 g,
Females: minimum 194 g, maximum 210 g.
- Housing: Group housing with up to 5 animals by sex in cages.
- Fasting period: From 16 hours before test start
- Diet (except for fasting period): Commercially available standard laboratory animal diet:
"Rat/Mouse Maintenance" from Altromin, Lage, Germany
- Water was provided ad libitum

ENVIRONMENTAL CONDITIONS

The animal room was maintained at:
- Temperature (°C): 22.5 ± 2.5°C
- Relative Humidity (%): 40 to 60%
- Photoperiod (artificial lighting): 12 h/day

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

- Dose formulation: 20% and 50% of the test material emulsified in the vehicle by warming it to 50°C and using an ultraturrax.
Administration of the dose formulation to the animals at body temperature.
- Dose volume: 1 mL / 100 g bw at each dose.
Individual dose volume was calculated based on individual bodyweight.
- For different doses and dose volumes, see Table 1 in "Any other information on materials and methods incl. tables"
- Rationale for doses selected: Based on a pre-test, which was not detailed in the study report.

Doses:

see Table 1 in "Any other information on materials and methods incl. tables"

No. of animals per sex per dose:

5

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations:
It has not been clearly specified in the report at what time points clinical signs and mortality were recorded, but the following records have been
reported:
Clinidal signs: At least shortly after dosing and over 8 hours after dosing (Day 0), and at 7 and 14 days post dosing.
Mortality: At least at 24 hours and 14 days post dosing.
Weighing of each animal: All animals on Day 0 for calculation of individual dose volume, and on Days 7 and 14 (end of observation period).
- Necropsy: All animals were necropsied at termination of the study.
- Control animals were untreated. As animals from a stock culture served as controls, apparently these were not necropsied concurrent with dosed animals.

Statistics:

LD50 was estimated for 24 hours and 14 days post dosing. Determination of a slope function was inappropriate as there were no deaths in both dose groups.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 515 mg/kg bw

Based on:

test mat.

Remarks:

WS400517

Remarks on result:

other: No deaths at 1006 or 2515 mg/kg.

Mortality:

There were no deaths during the 14-day observation period post dosing:
Single Dose of WS400517 at: Mortality
1006 mg/kg bw 0/5 (m); 0/5 (f)
2515 mg/kg bw 0/5 (m); 0/5 (f)

Clinical signs:

other: Shortly after dosing and 7 and 14 days afterwards clinical signs attributable to the treatment with the test material were not evident. Apathic behaviour, minimal in degree, was seen in the high dose group within 8 hours post dosing. This was not consider

Gross pathology:

Macroscopic pathology findings attributable to the treatment with the test material were not evident.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In view of the attained oral LD50 > 5000 mg/kg bodyweight for the test material equivalent to > 2515 mg/kg bodyweight for WS400517, the outcome of the present study does not necessitate any classification and labelling regarding acute oral toxicity according to EU regulations [DIRECTIVE 67/548/EEC and REGULATION (EC) 1272/2008]. In addition, sex-related differences in toxicity of the test material after single oral administration were not evident.