HDI oligomers, allophanate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Klimisch reliability of study is 1 (GLP guideline study); according to ECHA Practical Guide 6 rel. 2 is selected from the IUCLID pick-list as this should be the maximum score for read-across.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(2001)

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

197393-84-3

Cas Number:

197393-84-3

IUPAC Name:

197393-84-3

Constituent 2

Reference substance name:

900-066-9

EC Number:

900-066-9

IUPAC Name:

900-066-9

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Strain: Rat / Wistar / CrlGlxBrlHan:WI
- Source: Charles River Deutschland GmbH, Sandhofer Weg 7, 97633 Sulzfeld
- Age at study initiation: Young adult animals (female animals approx. 14 - 18 weeks)
- Weight at study initiation: 194 - 213 g
- Fasting period before study: Feed was withdrawn from the animals at least 16 hours before administration, but water was available ad libitum.
- Housing: Single housing in stainless steel wire mesh cages, type DK-lll (Becker & Co., Castrop-Rauxel, FRG)
- Diet: Kliba-Labordiät, Provimi Kliba SA, Kaiseraugst, Switzerland, ad libitum
- Water: Tap water ad libitum
- Acclimation period: Acclimatization for at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
Olive oil Ph.Eur./DAB
- Substance concentration in vehicle: 40g/100mL
- Administration volume: 5 mL/kg
- Justification for choice of vehicle: lnhomogeneous in watery preparation. Olive oil Ph.Eur./DAB had to be used to ensure homogeneity of the preparation.

Rationale for the selection of the starting dose: Based on the physical and chemical characteristics of the test substance and its composition, no pronounced acute oral toxicity was expected. Therefore, a starting dose of 2000 mg/kg body weight (limit test) has been chosen in the first step with 3 female animals.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: at least 14 days
- Frequency of observations and weighing:
Body weight determination: Individual body weights shortly before administration (day 0), weekly thereafter and at the end of the study.
Mortality: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
Signs and symptoms: Recording of signs and symptoms several times on the day of administration, at least once each workday for the individual animals.
- Necropsy with gross-pathology examination on the last day of the observation period after killing with CO2.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: No clinical observations were observed during clinical examination.

Body weight:

other body weight observations

Remarks:

The mean body weights of the administration groups increased throughout the study period.

Gross pathology:

No macroscopic pathologic abnormalities were noted in the animals examined at termination of the study.

Any other information on results incl. tables

For acute oral toxicity a read across from a substance with a very similar chemical composition (comparable allophanate-type HDI oligomerisation product, EC 900 -066 -9, CAS 197393 -84 -3) is applied. The read across is based on physicochemical and toxicological similarity of the two substances. Especially a recently conducted comparative pulmonary irritant potency study based on the recommendations of TRGS 430 (Technical Rule for Hazardous Substances 430, published by the German Federal Ministry of Labour and Social Affairs, last update 2009), confirmed for both allophanate-type HDI oligomerisation products the same toxicological mode of action and a nearly identical potency (both NOAEL at 3.4 mg/m³). For further justification of the grouping and read-across according to regulation (EC) No 1907/2006, Annex XI, 1.5 see document attached to chapter "Assessment Reports".

 

Applicant's summary and conclusion

Executive summary:

An acute oral toxicity study according to OECD TG 423 was conducted on female Wistar rats receiving a single dose of 2000 mg substance/kg bw via gavage administration. No mortality occurred. No clinical signs and findings were observed, and the mean body weights of the administration groups increased throughout the study period. No macroscopic pathologic abnormalities were noted in the animals examined at the end of the observation period. Thus, the LD50 was found to be > 2000 mg/kg bw.