Reaction product of Hexamethylene diisocyanate, oligomers with Mercaptopropyltrimethoxysilane

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2016-03-09 to 2016-05-11

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 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute 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:

male/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
- Weight at study initiation: preliminary study: 219 - 241 g; main study males: 257 - 286 g; females: 248 - 285 g
- Housing: During acclimatisation: 3 animals/sex/cage During the study: animals were housed individually. Type II polypropylene/polycarbonate; rat type cages with a solid floor, stainless steel wire covers and self-feeding baskets.
- Diet: ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum
- Water: tap water from watering bottles ad libitum
- Acclimation period: preliminary study: 13 days; main study males: 6 days; females 27 days

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

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

polyethylene glycol

Details on dermal exposure:

TEST SITE
- Area of exposure: back
- % coverage: approx. 10 %
- Type of wrap if used: plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: with body temperature water
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount applied: 2000, 300, 50, 5 mg/kg bw
- Concentration: 400, 60, 10, 1 mg/mL
- Constant volume or concentration used: yes

VEHICLE
- Lot/batch no.: 12J110516

Duration of exposure:

24 h

Doses:

Preliminary study: 5, 50, 300, 2000 mg/kg bw
Main study: 2000 mg/kg bw

No. of animals per sex per dose:

Preliminary study: 2 females
Main study: 5 males/females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days in main study
- Frequency of observations and weighing: inspection for signs of morbidity and mortality were made twice daily; weighing on day 0, 5 and 15; animals were observed individually 1 h and 5 h after dosing, and once each day for 14 days thereafter.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ appearance

Results and discussion

Preliminary study:

No mortality observed up to high dose. The data of main study were evaluated only.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred after the 24-hour dermal exposure to test item in Crl(WI)Br male and female rats during the study.

Clinical signs:

other: see Remark

Body weight:

lower than 10% body weight loss

Remarks:

Mean body weight development was within the normal range for male animals of this strain and age. A body weight loss was observed in female No.: 1195 treated with 2000 mg/kg bw test item between Day 0 and Day 7. The body weight loss was very slight (approx. 1.1 %).

Gross pathology:

All animals survived until the scheduled necropsy on Day 15.
Internal macroscopic changes were observed. A pale liver was detected in male animal No.: 1219, and pale kidneys were found in two male animals (No.: 1219, 1221). These alterations could not be related to the test item toxic effect, but were regarded an individual variation. Most likely the observations are a congenital anomaly.
Severe hydrometra was observed in two females (No.: 1195, 1196). Hydrometra is a physiological finding and connected to the cycle of the animal.
No macroscopic alterations due to the systemic toxic effects of the test item were found.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In this acute dermal toxicity study with the test item the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in Crl(WI)Br male and female rats. According to Regulation (EC) No 1272/2008 and UN GHS, the test item has not been classified into any category. On the other hand, it is to be noted that the test item caused dermal irritation response on the site of administration.

Executive summary:

An acute dermal toxicity study was performed with test item in Crl(WI)Br rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200. A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to test item at 2000 mg/kg bw by dermal route. The test item was applied in undiluted form and left in contact with the skin for 24 hours, followed by a 14-day observation period.

The results of the study were summarised as follows:

No mortality occurred after the 24-hour dermal exposure to the test item in male and female rats during the study.

Neither male nor female animals treated with 2000 mg/kg bw of the test item showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms as well defined and slight erythema in both sexes, between Day 1 and Day 5 in males and between Day 1 and Day 14 in females. Other dermal irritation symptom as dry skin, desquamation were recorded between Day 1 and Day 7 in males and between Day 1 and Day 8 in females and wounds were found in females between Day 6 and Day 14, as well. Mean body weight development was within the normal range for male animals of this strain and age. Slight body weight loss was observed in one female on first week. It was not evaluated as a toxic effect of the test item. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necropsy.