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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:
2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
equivalent or similar to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Name: Ethanol, 2,2'-oxybis-, reaction products with ammonia, morpholine derivs. residues
Physical state: liquid
Appearance: brown liquid
Specific details on test material used for the study:
- Name of test material (as cited in study report): Amine C-8
- Substance type: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan or any other USDA approved vendor
- Age at study initiation: 8-24 weeks at start of dosing; records of dates of birth for animals used in this study will be retained in the Calvert archives
- Weight at study initiation: 175 to 300 g at the outset (Day 1) of the study
- Fasting period before study: no data
- Housing: Animals are housed (group housed by sex upon receipt, 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 are kept is documented in the study records. No other species are kept in the same room.
- Diet (e.g. ad libitum): All animals have access to Harlan Teklad Rodent Diet (certified) or equivalent as per Calvert's SOP. The lot number and specifications of each lot used are archived at Calvert. No contaminants are 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 (e.g. ad libitum): Tap water is 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 are 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 is maintained in the Calvert archives.
- Acclimation period: Study animals will be acclimated to their housing for a minimum of 5 days prior to their first day of dosing.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22° ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:
occlusive
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: > or = 10%
- Type of wrap if used: the test article is applied on an intact skin site for each animal, covered with a gauze patch/dental dam, wrapped with an elastic bandage and secured with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): post-exposure, the site is unwrapped and wiped approximately to remove residual test article
- Time after start of exposure: no data

TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Constant volume or concentration used: yes/no
- For solids, paste formed: yes/no

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:
Duration of exposure:
Applied once and remains in contact with the skin for twenty-four ± 0.5 hours.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/morbidity: once daily; each animal is observed for evidence of death or impending death as per Calvert SOP VET-14
Clinical observations: Clinical observations are recorded immediately after unwrap, and daily thereafter through Day 15. At the time of clinical observations, the dose site is evaluated for dermal irritation. If present, dermal irritation is scored and recorded. In addition to the observation of irritation, any leions and other toxic effects are fully described. Additional clipping of the fur may be conducted as needed to facilitate dermal observations.
Body weight: Animals are weighed prior to dosing on Day 1 and on Days 8 and 15 or upon death
- Necropsy of survivors performed: yes
Statistics:
Body weights will be summarized using descriptive statistics (mean and standard deviation). if the data allow, the LD50 with 95% confidence limits are calculated by the method of Litchfield and Wilcoxin. When the data permits, the LD50 is calculated for each sex.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortalities
Mortality:
no mortalities observed
Clinical signs:
On the second day after exposure: all animals showed abnormal gait. One animal showed dark fur around eyes.
Abnormal gait continued untill day 3 in one animal. all animals appeared normal from day 4 till the end of the observation period.
Body weight:
normal body weight gain
Gross pathology:
no visible lesions
Other findings:
Day 2 of observation period:
All females (5/5) and 1 male (1/5) showed well defined erythema and slight edema. Other males showed moderate to severe erythema and slight edema.

day 3 -7
All males showed moderate to severe erythema and moderate edema. All females showed moderate to severe erythema and edema.

day 8 -15
Effects disappeared in males (no or very slight erythema, no edema) while in females the effects increased. 4 out of 5 females showed necrosis and sloughing from day 10. One animal showed no erythema or edema.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
There were no mortalities observed after acute dermal exposure to 2000 mg/kg bw/d of the test substance in 10 rats. Shortly after exposure, local erythema and edema effects were observed in both males and females. The effects seemed to be reversible in males and 1 female. In the 4 other females, necrosis and slouching appeared.