Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 April 2009 - 21 April 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP Guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Daltolac XR 159
- Lot/batch No.: RZW023
- Expiration date of the lot/batch: Twenty-one months at customer
- Physical Description: Light yellow viscous liquid
- Composition/Purity: Reaction mass of 2,2'-Oxydiethanol, propoxylated and formaldehyde polymer with benzenamine and 2-methyloxirane
Stability: The test article was expected to be stable under standard laboratory conditions for the duration of testing.
Storage Conditions: Room temperature (10-30ºC)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Total Number: Ten
Gender: Male and female
Age Range: 7 to 8 weeks; records of dates of birth for animals used in this study are retained in the Calvert archives.
Body Weight Range: 172 to 239 grams
Animal Source: Harlan
Experimental History: Purpose-bred and experimentally naïve at the outset of the study.
Identification: Ear tag and cage card.

ENVIRONMENTAL CONDITIONS
Housing: Animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council “Guide for the Care and Use of Laboratory Animals”. Calvert is a USDA registered and fully AAALAC accredited facility. The room in which the animals were kept was documented in the study records. No other species were kept in the same room.
Lighting: 12 hours light/12 hours dark
Room Temperature: 17.2 to 26.7°C
Relative Humidity: 10 to 67%
Food: All animals had access to Harlan Teklad Rodent Diet (certified) as per Calvert SOP. Animals were fasted overnight prior to dose administration. Food was returned to the animals ~30 minutes after dosing. The lot number(s) and specifications of each lot used are archived at Calvert. No contaminants were known to be present in the certified diet at levels that would be expected to interfere with the results of this study. Analysis of the diet was limited to that performed by the manufacturer, records of which are maintained in the Calvert archives.
Water: Tap water was available ad libitum, to each animal via an automatic watering device. The water is routinely analyzed for contaminants as per Calvert SOP’s. No contaminants were known to be present in the water at levels that would be expected to interfere with the results of this study. Results of the water analysis are maintained in the Calvert archives.
Acclimation: Study animals were acclimated to their housing for a minimum of 5 days prior to dosing.

IN-LIFE DATES: From: 6 April 2009 To: 21 April 2009

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Route: dermal on intact skin sites
Frequency: applied once and remained in contact with skin site for 24 hours. After exposure the sites were unwrapped and wiped with mineral oil and gauze to remove residual test article.
Dose levels: Dosage levels were calculated on a mg/kg basis for each individual animal based on body weight. One group of animals received the test article at 2000 mg/kg.
Procedure: On the day prior to application on the test article, fur was clipped from the dorsal area of the trunk of the test animals. Care was taken to avoid abrading the skin, which could alter its permeability. A sufficient area (>10%) was cleared for application of the test material under a gauze patch. The test article was applied as received, covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
One group:
5 males
5 females
Control animals:
no
Details on study design:
- One group of ten rats (5 males and 5 females) received Daltolac XR 159 dermally at a dose level of 2000 mg/kg.
-Mortality: The mortality checks were made twice daily.
-Clinical observations: Observations were recorded immediately, 1, 2, 5 and 4 hours post-unwrap, and daily thereafter through Day 15.
- Body weights: They were recorded on the day of dosing (Day 1), and on Days 8 and 15.

All rats were euthanized by CO2 asphyxiation and necropsied on Day 15.
Statistics:
The design of this study was such that statistical analysis was not necessary.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality was not observed in any of the animals at 2000 mg/kg.
Clinical signs:
No clinical signs were observed during the study. No signs of irritation were observed during the study.
Body weight:
No biologically significant effect was seen on body weights of animals on Days 8 and 15. All animals gained weight during the course of the study.
Gross pathology:
No visible lesions were observed in any of the animals at terminal necropsy.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
Based on the results of this study, the acute dermal LD50 for Daltolac XR 159 in rats was estimated to be greater than 2000 mg/kg.
Executive summary:

The purpose of this study was to evaluate the potential toxicity or to determine the median lethal dose (LD50) of a test article following a single administration via the dermal route.

One group of ten Sprague-Dawley rats (five males and five females) were exposed one time to the test article dermally at a dose level of 2000 mg/kg. Mortality checks were made twice daily. Clinical observations were recorded immediately, 1, 2.5 and 4 hours post-unwrap, and daily thereafter through Day 15. Body weights were recorded on the day of dosing (Day 1), and on Days 8 and 15. All rats were euthanized by CO2asphyxiation and necropsied on Day 15.

No abnormal clinical signs were observed during the study. No erythema or edema at the application sites was observed during the study. No mortality was observed during the study. No biologically significant effect was seen on body weight in the animals on Days 8 and 15. No visible lesions were observed in any of the animals at terminal necropsy.