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Description of key information

Based on the available information from the key acute oral toxicity study, the LD50 (oral, rat) for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate was concluded to be > 2000 mg/kg bw. The study was conducted according to OECD Test Guideline 423 and to GLP (BSL Bioservice 2012a). Based on the available information from the key acute dermal toxicity study, the LD50 (dermal, rat) for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate was concluded to be > 2000 mg/kg bw. The study was conducted according to OECD Test Guideline 423 and to GLP (BSL Bioservice 2013a). 

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 April - 6 June 2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: Wistar rats Crl: WI (Han)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 160-181 g
- Fasting period before study: 16-19 hours
- Housing: in groups in IVC cages, type III H, polysulphone cages
- Diet: Altronim 1324 maintenance diet for rats and mice, ad libitum
- Water: tap water, sulphur acidified to a pH value of 2.8, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 3
- Humidity (%): 55 +/- 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
The liquid test item was tested undiluted.
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg bw

Doses:
The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1 or 2 of the test guideline. Based on these results and according to the acute toxic class method regime no further testing was required.
No. of animals per sex per dose:
6 (female)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: on day 1 (prior to administration), day 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: observation at 30 minutes, 4 hours, then every day post-administration. Attention was paid to changes in skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality was observed during the 14-day period of study.
Clinical signs:
No clinical changes were observed during the 14-day study period.
Body weight:
No weight loss in any of the animals was reported during the 14-day study period.
Gross pathology:
No pathological changes were observed in any of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study conducted to the OECD 402 and to GLP, the LD50 for 2,4-hexadienoic acid, 3-(trimethoxysilyl)propyl ester was > 2000 mg/kg bw in rats.
Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was tested undiluted and administered at a dose volume of 2 mL/kg. All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically. All animals survived until the end of the study without showing any test-item related signs of toxicity. Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain. At necropsy, no macroscopic findings were observed in any animal of any step. Under the conditions of the present study, a single oral application of the test item to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality. Therefore, the LD50 for this test item is expected to be greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15/01/2013 - 02/02/2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1100 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: WISTAR rats Crl: WI(Han) (full barrier)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River, Germany
- Age at study initiation: 8-9 weeks
- Weight at study initiation: males 237-259 g ; females 166-183 g
- Fasting period before study: none
- Housing: The rats were kept individually in IVC cages, type IP H, polysulphone cages on Altromin saw fibre bedding.
- Diet (e.g. ad libitum): Altromin 1324 maintenance diet for rats and mice
- Water (e.g. ad libitum): tap water, sulphur acidified to a pH value of approx. 2.8
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10
- Type of wrap if used: gauze-dressing and non-irritating tape plus additional dressing

REMOVAL OF TEST SUBSTANCE
- Washing: yes
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg per body weight
- Constant volume or concentration used: yes


Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 non-pregnant females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighed on day 1 (prior to the application), on days 8 and 15. Observations for clinical signs were noted 30 minutes after application, then at 4 hours and then daily. Special attention was paid to changes in the skin and fur, eyes and mucous membranes, circulatory, respiratory, autonomic and central nervous system as well as somatomotor activity and behaviour pattern were examined.
- Necropsy of survivors performed: At the end of the study all the surviving animals were killed by overdosage with pentobabrital injected intraperitoneally. All gross pathological changes were recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no cases of mortality during the 14-day study period.
Clinical signs:
There were cases of eschar or scratches from day 5 until day 12 in one male. The same effect was observed in 4 females from day 5 until days 9, 15, 7 and 12.
Body weight:
A slight gain of body weight was observed in both males and females during the 14-day study period.
Gross pathology:
No significant gross pathological changes were recorded in the tested animals.
Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study conducted to the OECD 402 and to GLP, the LD50 for 2,4-hexadienoic acid, 3-(trimethoxysilyl)propyl ester was > 2000 mg/kg bw in rats.

Executive summary:

The acute dermal toxicity following the application of a single dose of the test item was determined. The study was performed as a limit test according to OECD 402 and OPPTS 870.1200.

Five male and five female WISTAR Crl: (WI(Han) rats were selected for testing. The fur was removed from the dorsal area of the trunk using an electric clipper. Care was taken to avoid abrading the skin, and only animals with healthy intact skin were used. At least 10% of the body surface was cleared for the application. Prior to application, a detailed clinical observation was made for all animals.

The neat test item was applied uniformly over an area which was approximately 10% of the total body surface. The test item was held in contact with the skin by a dressing throughout the 24 hour period. The dressing consisted of a gauze-dressing and not-irritating tape and was fixed with an additional dressing in a suitable manner.

Under the conditions of the study, single dermal application of the test item to rats at a dose of 2000 mg/kg body weight was associated with neither mortality nor signs of toxicity but signs of irritation. Therefore, the dermal LD50 was determined to be >2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Based on the available information from the key acute oral toxicity study, the LD50 (oral, rat) for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate was concluded to be > 2000 mg/kg bw (BSL Bioservice 2012a).

Following oral administration of 2000 mg/kg bw of the test material to 6 female rats, no mortality, clinical changes, body weight loss or pathological changes were observed during the 14 -day study period.

Based on the available information from the key acute dermal toxicity study LD50 (dermal, rat) for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate was concluded to be > 2000 mg/kg bw (BSL Bioservice 2013a).

Following cutaneous application of 2000 mg/kg bw to the skin of 10 male/female rats, no mortality was observed during the 14 -day study period. Eschar or scratches were observed in 1 male and 5 females from day 5 until day 12 of the observation period. No body weight or pathological changes were noted during the study.


Justification for classification or non-classification

Based on the available data for 3-(trimethoxysilyl)propyl-(2E,4E)-hexa-2,4-dienoate, no classification for acute oral and dermal toxicity is required, according to Regulation (EC) No. 1272/2008.