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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
2008
Deviations:
no
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

Constituent 1
Reference substance name:
Reaction product of Hexamethylene diisocyanate, oligomers with Mercaptopropyltrimethoxysilane
EC Number:
924-669-1
Cas Number:
192526-20-8
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:
General symptoms: No behavioural changes or systemic toxic signs were noted during the study.

Dermal irritation symptom as erythema and other signs as dry skin, desquamation and wounds were observed on the treatment site. Well defined erythema (score 2) appeared in all males and females. It was detectable between Day 1 and Day 3 in males and between Day 1 and Day 6 in females. A slight redness (score +1) was observed between Day 2 and Day 5 in males and between Day 5 and Day 14 in females. Dry skin and desquamation were found in all animals. Dry skin occurred between Day 1 and Day 7 in males and between Day 1 and Day 8 in females. Desquamation was detected between Day 1 and Day 2 in males and between Day 1 and Day 8 in females. Wounds were recorded in all females between Day 6 and Day 14. All males were free of symptoms between Day 8 and Day 14 and three females (No.: 1194, 1192, 1193) became free of symptoms between Day 9 and Day 14.
Body weight:
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.

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