Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
29 September 2011 to 18 October 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands
- Age at study initiation: 9 weeks (males), 11 weeks (females)
- Weight at study initiation: 225.1 to 234.5 g (males), 201.3 to 216.2 g (females)
- Fasting period before study: no data
- Housing: in groups of three in Makrolon type 4 cages
- Diet (e.g. ad libitum): pellet diet ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 3
- Humidity (%): 30 to 70
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 29 September 2011 To: 18 October 2011

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: ~ 5 x 5 cm
- % coverage: 10
- Type of wrap if used: gauze pad held in place by adhesive hypoallergenic aerated dressing and elastic adhesive restrainer bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4 ml/kg bw
- Constant volume or concentration used: no
Duration of exposure:
24 h
Doses:
4000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 15 days (day of treatment (day 1) and up until 14 days after patch removal (days 2 to 15))
- Frequency of observations and weighing: Clinical signs and mortality assessed within first 30 minutes and 1, 2, 3 and 5 hours after treatment, and on days 2 to 15 (daily for clinical signs, twice daily for mortality). Skin observed daily during test days 2 to 15 (re-clipped on days 4, 8, 10 and 14). Body weights recorded on day 1 (prior to treatment), 8 and 15.
- Necropsy of survivors performed: yes
Statistics:
No statistical analysis was performed

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality observed throughout the study
Mortality:
There were no deaths over the course of the study.
Clinical signs:
Slightly increased activity noted in all males and females 1 and 2 hours after treatment on day 1.
5 hours after treatment, dragging of limbs seen in all animals and still seen on day 2 in all males and four females, persisting up to day 3 in two males.
Slight/moderately decreased activity noted on day 2 and/or 3.
Severely decreased activity on day 2 in one female, with decreased severity (slight) noted on day 4. Also reduced temperature, vocalisation and shivering noted on day 2 in this animal.
Body weight:
No effects on body weight were reported.
Gross pathology:
No macroscopic findings recorded at necropsy.
Other findings:
- Other observations: Slight erythema was seen in four males during the first days after treatment. Focal crusts were additionally seen in three of these males and slight desquamation in one. All these symptoms reverted by day 8. Slight to moderate erythema in females, persisting up until day 13/14 in two animals. Slight to severe focal crusts were seen in all animals, and persisted in two females up until test day 15. Slight to severe desquamation was seen in four females, and slight to moderate necrosis in two females. In one female, desquamation was still seen at day 15.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a study carried out in accordance with OECD Test Guideline 402 and in compliance with GLP, triethoxy(3-thiocyanatopropyl)silane was of low toxicity to rats following a 24-hour dermal application. The acute dermal LD50 was determined to be greater than 4000 mg/kg bw.
Executive summary:

In a GLP-compliant study carried out in accordance with OECD Test Guideline 402, triethoxy(3-thiocyanatopropyl)silane was assessed for its dermal toxicity in rats.

The test material was applied semi-occlusive to the clipped skin of five male and five female Wistar rats at 4000 mg/kg bw for 24 hours (day 1). Rats were then observed for clinical signs of toxicity and mortality for a further 14 days (days 2 to 15), before sacrifice and gross necropsy.

 

No mortality occurred and no significant gross macroscopic or body weight changes were reported. Dragging of limbs was noted in all animals within a day of application. This persisted until day two in females except from one female and to day three in two males. A sigificant increased activity was observed in all animals shortly after treatment, while decreased activity was noted on days two and three. More severe effects (severely decreased activity, reduced temperature, vocalisation and shivering) were observed in one female on day two.

 

Some males demonstrated reversible skin effects (slight erythema and focal crusts, with slight desquamation in one), which reverted within eight days of application. Skin effects were more pronounced in females (slight to moderate erythema, slight to severe focal crusts, slight to severe desquamation, and slight to moderate necrosis), with some effects lasting up until day 15 (focal crusts in two animals, desquamation in one).

 

Triethoxy(3-thiocyanatopropyl)silane was of low systemic toxicity when applied to the skin of male and female rats for 24 hours. The acute dermal LD50 was determined to be greater than 4000 mg/kg bw.