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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2001
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2001
Report Date:
2001

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
The drinking water for the animals was meant to be treated by reverse osmosis, but was not. This incident did not affect the quality or integrity of the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Remarks:
clear, colourless

Test animals

Species:
rat
Strain:
other: Crl:CD(R)(SD)IGS BR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Charles River Laboratories, Raleigh, NC

- Age at study initiation: 11 weeks old (males) and 12 weeks old (females) at initiation of dosing

- Weight at study initiation: 325 to 339 grams (males) and 219 to 263 grams (females) at initiation of dosing.

- Housing: Individual suspended wire-mesh cages. The animals were maintained by the animal husbandry staff of WIL Research Laboratories Inc., in accordance with standard operating procedures.

- Diet: Certified Rodent LabDiet 5002, ad libitum (PMI Nutrition International, Inc.)

- Water: Municipal water, ad libitum.

ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68-74 (20-23.3°C)

- Humidity (%): 33-60 %

- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light


Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE

- Area of exposure: dorsal skin

- % coverage: 16-20% body surface

- Type of wrap if used: Gauze binders, secured with non-irritating tape.


REMOVAL OF TEST SUBSTANCE

- Washing: The bandages were removed and the sites were wiped with disposable paper towels moistened with tap water.

- Time after start of exposure: 24 hours

TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 2000 mg/kg

- Concentration (if solution): undiluted

- Constant volume or concentration used: Individual doses were calculated based on body weights taken just prior to dosing and the dose volume of 1.9 ml/kg.



Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for overt signs of toxicity at 1, 3, and 4 hours and once daily, thereafter, for a total of 14 days. Animals were observed twice daily for mortality.  The degree of erythema and eschar formation and edema at the application site was assessed 30-60 minutes after exposure and at daily intervals. Thereafter, using a 0-to-4-severity scale for each criterion. Body weights were recorded on days 0, 7, and 14. 

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other:  On day 14, animals were sacrificed and subjected to gross necropsy and examination of the cranial, thoracic and abdominal cavities.
Statistics:
No statistical analysis was included in the report.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths during the study.
Clinical signs:
Five animals were noted with wet and/or dried red, yellow and/or brown material around the nose, eye(s), base of tail and/or urogenital areas on study days 0 and/or 1. These findings are typically noted in association with the bandage application procedures and were not considered to be related to the test article. Additionally, a single animal was noted with an isolated occurrence of soft feces on study day 1. There were no other clinical findings.
Body weight:
All females lost from 2-16 grams (1-7%) of initial (study day 0) body weigh during the first week of the study. All animals gained weight during the second week and with the exception of one female, which was within 8 grams (3%) of its initial body weight, had surpassed their initial body weight. These losses were slight and, with the absence of other signs of systemic toxicity, were not considered to be a result of the test article. There were no other remarkable body weight changes noted during the study.
Gross pathology:
There were no gross necropsy findings for any examined tissues.
Other findings:
- Other observations: Very slight erythema and very slight edema were noted for seven and four animals, respectively, which completely subsided by study day 5. Desquamation was observed sporadically for five animals during study days 2-7. There were no other dermal findings noted during the study.

Any other information on results incl. tables

The LD50 was determined to be greater than 2000 mg/kg bw. These findings indicate that 3-(trimethoxysilyl)propyl methacrylate has a very low order of acute percutaneous toxicity.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal toxicity study, conducted according to OECD 402 and in compliance with GLP, an LD50 value of >2000 mg/kg was determined in a reliable study.