Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
31 October 2007 to 15 November 2007
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2008
Report Date:
2008

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
- animal room humidity was outside the preferred range of 30-70 %. Erythema grade 1 was also documented with a score of maximized grade 4, however per protocol, due to an eschar score of >1, a maximized grade 4 is the only erythema grade needed.
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
- animal room humidity was outside the preferred range of 30-70 %. Erythema grade 1 was also documented with a score of maximized grade 4, however per protocol, due to an eschar score of >1, a maximized grade 4 is the only erythema grade needed.
Principles of method if other than guideline:
The deviations detailed above are not considered to have an impact on the validity of the study.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Sponsor's identification: AS305BD
Description: dark brown, viscous liquid
Lot number: TS07002
Analytical purity: 100%
Storage conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Portage, MI
- Age at study initiation: approximately 10 weeks
- Weight at study initiation: 344-296 g prior to dosing (males); 227-252 g prior to dosing (females)
- Fasting period before study:
- Housing: individually in suspended stainless steel cages
- Diet (e.g. ad libitum): PMI Certified Rodent Chow #5002 (PMI Nutrition International) ad libitum
- Water (e.g. ad libitum): municipal tap water ad libitum
- Acclimation period: a minimum of five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23
- Humidity (%): 16059
- Air changes (per hr): 10-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hour light/12 hour dark

IN-LIFE DATES: From: 1st November 2007 To: 15th November 2007

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal trunk area
- % coverage: approximately 10%
- Type of wrap if used: test material was held in contact with the skin with an appropriately sized 4-ply porous gauze dressing backed with plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): using a gauze mositened with mineral oil, USP, followed by dry gauze, followed by gauze moistened with deionized water, followed by dry gauze
- Time after start of exposure: approximately 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): dose volume = 2.08 mL/kg
Duration of exposure:
Approximately 24 hours exposure; 14 days for observations
Doses:
Single dermal administration of the test article at a dose level of 2000 mg/kg body weight
No. of animals per sex per dose:
Five male and five female rats
Control animals:
yes, concurrent no treatment
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: test animals examined for erythema and edema after patch removal on day 1 and daily thereafter. Test animals examined for clinical abnormalities a mimnimum of two days on study day 0 and daily thereafter. Individual bodyweights obtained prior to dosing on day 0, day 7 and day 14.
- Necropsy of survivors performed: yes
Statistics:
Based on the results of each dose level, the LD50 was estimated as follows:

- <50% mortality - LD50 was estimated as greater than the administered dose
- =50% mortality - LD50 was estimated as equal to the administered dose
- >50% mortality - LD50 was estimated as less than the administered dose

Bodyweight means and standard deviations were calculated separately for males and females.

Results and discussion

Preliminary study:
Not applicable.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
Transient incidences of dark material around the facial area, hair loss, labored breathing, aggressiveness, urine stain, and few feces
Body weight:
Two males and one female had a slight body weight loss on day 7, but all animals gained body weight by the end of the test period
Gross pathology:
Mandibular lymph node foci and a raised area of the skull both of which were noted in one female animal. Scabs and flaking of the treated skin were also noted at necropsy. External findings of hair loss (of the forelimbs) were noted in one female at necroscopy.
Other findings:
Dermal irritation consisted of erythema maximized grade 4 (with notable dermal lesion of blanching), which was noted in all animals during the study and diminished to well-defined erythema in 4 males or to slight erythema in 1 male and 5 females. Slight edema was noted in 3 males and 3 females and very slight edema was noted in 5 males and 5 females during the study. Desquamation (all animals), superficial lightening (2 males and 3 females), blanching (all animals), and eschar (3 males and 5 females) were also noted during the study.

Applicant's summary and conclusion

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
Under the conditions of this test, the acute dermal LD50 of AS305BD was estimated to be greater than 2000 mg/kg in the rat.
Executive summary:

An acute dermal toxicity study was performed on male and female rats at a single dose of 2000 mg/kg bodyweight in line with OCED Guideline 402.

No mortality occurred during the study. A number of clinical observations were observed during the study. Dermal irritation consisted of erythema maximized grade 4 (with notable dermal lesion of blanching), which was noted in all animals during the study and diminished to well-defined erythema in 4 males or to slight erythema in 1 male and 5 females. Slight edema was noted in 3 males and 3 females and very slight edema was noted in 5 males and 5 females during the study. Desquamation (all animals), superficial lightening (2 males and 3 females), blanching (all animals), and eschar (3 males and 5 females) were also noted during the study. Two males and one female had slight body weight loss at day 7 but all animals gained body weight by the end of the study.

Under the conditions of the study, the acute detmal LD50 of AS305BD was estimated to be > 2000 mg/kg in the rat.