Reaction product of Hexamethylene diisocyanate, oligomers with Mercaptopropyltrimethoxysilane

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-02-29 to 2016-05-02

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

2002

Deviations:

no

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:

Reaction product of Hexamethylene diisocyanate, oligomers with Mercaptopropyltrimethoxysilane

EC Number:

924-669-1

Molecular formula:

No data available

IUPAC Name:

Reaction product of Hexamethylene diisocyanate, oligomers with Mercaptopropyltrimethoxysilane

Test material form:

liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Young adult rats, 9 weeks old in group 1 and group 2
- Weight at study initiation: 227 - 233 g
- Fasting period before study: The day before treatment the animals were fasted. The food but not water was withheld overnight. Animals were weighed before the application and the food was given back 3 hours after the treatment.
- Housing: 3 animals/sex/cage; cage type: Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.
- Diet: The animals received ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum. The food is periodically analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in Toxi-Coop Zrt.’s archive.
- Water: Animals received tap water from watering bottles ad libitum. The drinking water is periodically analysed and is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study. Copies of the relevant Certificates of Analysis are maintained in Toxi-Coop Zrt.’s archive.
- Acclimation period: 13 days in first step and 14 days in second step.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: above 10 air exchanges/hour by central air-condition system.
- Photoperiod: Artificial light, from 6 am. to 6 pm.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 mg/mL
- Lot/batch no.: 12J110516

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: The starting dose was selected on the basis of the available information about the test item.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed individually after dosing once during the first 30 minutes, then 1 h, 2 h, 3 h, 4 h, after the treatment and once per day for 14 days thereafter. The body weight were recorded on day 0 (shortly before the treatment), on day 7 and on day 15 on all animals with a precision of 1 g, respectively.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The test item did not induce mortality following a single oral administration to female rats at a dose of 2000 mg/kg bw. All female rats survived the performed treatment until the end of the 14-day observation period.

Clinical signs:

other: In group 1 and 2 (2000 mg/kg bw) the mean body weight and body weight gain of the animals corresponded to their species and age throughout the study.

Gross pathology:

All animals treated with 2000 mg/kg bw dose of test item survived until the scheduled necropsy on Day 15. Internal necropsy finding as pale kidneys was observed in animal No.: 1169 of group 2. This alteration could not be related to the test item toxic effect, but was regarded an individual variation. Most likely the observation is a congenital anomaly. Severe hydrometra was found in two females (No.: 1169, 1172) of the group 2. Hydrometra is physiological finding and connected to the cycle of the animals. No pathological changes were found related to the effect of the test item during the macroscopic examination of animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The method used is not intended to allow for the calculation of a precise LD50 value. However for this acute oral toxicity study with the test item in rats the determined LD50 is above 2000 mg/kg bw. Thus, the test item is ranked into classes of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423 as not classified.

Executive summary:

An acute oral toxicity study was carried out using the class method according to OECD guideline 423. The starting dose was selected on the basis of the available information about the test item. The acute toxic class method was carried out involving a stepwise procedure with the use of 2000 mg/kg bw as the starting dose in three female rats. No animal died in the first step at 2000 mg/kg bw dose level. Therefore, treatment with 2000 mg/kg bw was repeated on further three female rats. Again, no animal died in the second step, thus, no further testing was required. The stopping criteria of Annex 2d of OECD Guideline No. 423 (presented in Appendix 7) were met. Animals were weighed, observed for lethality and toxic symptoms for 14 days after the treatment. Gross pathological examination was carried out on 15th day after the treatment. No lethality was noted following oral administration of a single dose of 2000 mg/kg bw. In the first and second step at a dose level of 2000 mg/kg bw no clinical symptoms were observed on the day of the treatment and during the 14-day observation period, the general state and behaviour of experimental animals were normal. The body weight development was normal in all animals. All organs of the animals treated with 2000 mg/kg bw dose proved to be free of treatment related gross pathological changes.