Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17-Jul-2009 to 05-Oct-2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
This study has been performed in compliance with the Swiss Ordinance relating to Good Laboratory Practice, adopted May 18th, 2005 [SR 813.112.1]. This Ordinance is based on the OECD Principles of Good Laboratory Practice, as revised in 1997 and adopted November 26th, 1997 by decision of the OECD Council [C(97)186/Final]. These principles are compatible with Good Laboratory Practice regulations specified by regulatory authorities throughout the European Community, the United States (EPA and FDA), and Japan (MHLW, MAFF and METI).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

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))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
other: HsdHan: WIST(SPF)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM Horst / The Netherlands, 5960 AD Horst / The Netherlands
- Age at study initiation: fales: 9 weeks, females: 11 weeks
- Weight at study initiation: males: 231.9 g – 263.8 g, females: 188.0 g – 203.6 g
- Housing: during acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494, Rosenberg / Germany, imported by Provimi Kliba
AG, 4303 Kaiseraugst / Switzerland) during treatment and observation.
- Diet (e.g. ad libitum): Pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 15/09 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum.
- Water (e.g. ad libitum): Community tap water from Füllinsdorf ad libitum.
- Acclimatation period: 17-Jun-2009 to 22-Jun-2009 (one male, one female), 17-Jun-2009 to 23-Jun-2009 (four males, four females)


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


IN-LIFE DATES: From: 23-Jun-2009 To: 08-Jul-2009

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: approx. 25 cm2
- % coverage: approximately 10% of the total body surface
- Type of wrap if used: semi-occlusive dressing wrapped around the abdomen and fixed with an elastic adhesive bandage.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): after the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels.
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Due to the correction factor of 2.42 based on the monomer purity. Application volume was adjusted to 4.36 mL/kg (x 1110 mg/ml = 2000 mg/kg).
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 (see Table 1)
Control animals:
not required
Details on study design:
A single animal of each sex was treated first. Since neither severe local effects nor severe systemic symptoms were observed after the 24-hour exposure, the test was completed using the remaining four male and four female animals for an exposure period of 24 hours.
- Duration of observation period following administration: 15 days in group 1, 14 days in group 2
- Frequency of observations and weighing: The male and the female of group 1 were re-shaved on test days 4, 9 and 15 and all animals of group 2 on test day 3, 8 and 14 to facilitate the reading of the local reactions.
- Necropsy of survivors performed: yes
- Other examinations performed: Viability / Mortality, Clinical Signs, Local Dermal Sign, Body Weights

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
other: Dose adjusted for content of the main constituent, and density.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 4 840 mg/kg bw
Based on:
test mat.
Remarks:
as is : Dose of substance as registered (including impurities and residual water necessary for the stability)
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs or local dermal signs were observed during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were observed at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The median lethal dose of TRIQUAT Monomer after single dermal administration to rats of both
sexes, observed over a period of 14 days is: LD50 (rat) greater than 2000 mg/kg body weight
Executive summary:

A group of 1 male and 1 female and a second group of 4 males and 4 females HsdHan: WIST(SPF) rats were treated with TRIQUAT Monomer at 2000 mg/kg by dermal application. The test item was applied undiluted as delivered from the Sponsor at a volume dosage of 4.36

mL/kg, taking into account the purity of the test item of 41.25% (correction factor 2.42) and the test item density of 1.11 g/mL. The application period was 24 hours.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after treatment on day 1 and once daily

during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-

15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

No deaths occurred during the study.

No clinical signs or local dermal signs were observed during the course of the study.

The body weight of the animals was within the range commonly recorded for this strain and age.

No macroscopic findings were observed at necropsy.