Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - May 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

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

Test material

Constituent 1
Chemical structure
Reference substance name:
1,1-dimethylurea
EC Number:
209-957-0
EC Name:
1,1-dimethylurea
Cas Number:
598-94-7
Molecular formula:
C3H8N2O
IUPAC Name:
1,1-dimethylurea
impurity 1
Chemical structure
Reference substance name:
Urea
EC Number:
200-315-5
EC Name:
Urea
Cas Number:
57-13-6
Molecular formula:
CH4N2O
IUPAC Name:
urea
impurity 2
Chemical structure
Reference substance name:
Water
EC Number:
231-791-2
EC Name:
Water
Cas Number:
7732-18-5
Molecular formula:
H2O
IUPAC Name:
dihydrogen oxide
Test material form:
solid: crystalline
Specific details on test material used for the study:
- Name of test material (as cited in study report): 1,1-dimethylurea
- Physical state: solid
- Analytical purity: 99.9 %
- Lot/batch No.: 301601

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: BeiJing Vital River Laboratory Animal Technology Co., Ltd.
- Age at study initiation: 49-62 days on arrival, in the range of 8-12 weeks at the commencement of each animal’s dosing.
- Weight at study initiation: Males: 261-298 g,Females: 235-261 g, and weight variation was not exceed ± 20% of the mean body weight at grouping.
- Housing: Animals were raised in suspended, stainless steel cages (L 32.0 cm × W 28.0 cm × H 20.0 cm) on cage racks (L 167.0 cm × W 70.0 cm × H 171.0 cm). There were 10 cages per layer, and 4 layers per rack. Animals were housed individually during the test.
- Diet (e.g. ad libitum): Animals were provided with sterilized diet with complete nutrition supplied by Beijing keaoxieli Feed Co., Ltd. (Product License No: SCXK(jing) 2012-0001, Batch NO. 14013213); ad libitum
- Water (e.g. ad libitum): Water was purified by HT-R01000 purity system. Water analysis was conducted routinely analyzed (annually), and all parameters except pH were within the permitted limits described in the national drinking water standard (GB5749-2006) and pH was within the permitted limits described in the purified water standard (GB17324-2003); ad libitum
- Acclimation period: 8 days prior to the test

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.0-23.7℃
- Humidity (%): 40%-63%
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal Area of the trunk
- coverage: 5 cm x 5.5 cm
- Type of wrap if used: white medical tape (non-irritating)

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period for approximated 24 hours, residual test item was removed by using water

:
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
five males and five females
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Individual weights of animals were determined at grouping, on Day 0 (day of dosing), Day 7 and 14. Changes in weight were calculated and recorded.
- Necropsy of survivors performed: yes
Clinical observations were performed once during the first 30 min, and at 1, 2 and 4 hours after application and then once each day for 14 days.
Careful observation and record of animal fur changes, eyes and mucosa, respiratory, circulatory, autonomic and central nervous system, particularly limb activity and behavior change was made.
Particular attention was directed to observations of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.

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 death or moribund animals during the test.
Clinical signs:
There were no abnormal findings in all animals after dosing from the first day until the end of the test.
Body weight:
Only one animal showed a very small decrease of body weight during the first week. But overall also this animal showed growth during the whole observation period.The results indicated that the body weight gain of all animals showed growth.
Gross pathology:
No abnormalities were found at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Based on the results, the acute dermal LD50 in rats for 1,1-dimethylurea was as follows:
Male rats: > 2000 mg/kg b.w.
Female rats: > 2000 mg/kg b.w.
Executive summary:

A study was performed to assess the acute dermal toxicity of 1,1 -Dimethylurea in Sprague Dawley rats. The method was designed to meet the OECD Guideline for Testing of Chemicals: Acute Dermal Toxicity (No.402, adopted 1987).

A limit test at one dose level of 2000 mg/kg body weight was carried out in a group of 10 animals (5 males and 5 females). Clinical observations were made once during the first 30 min, and at 1, 2 and 4 hours after dosing and then once each day for up to 14 days. Individual weights of animals were determined at grouping, before dosing (Day 0), on day 7 and 14. At the end of the test, a gross necropsy was performed on all test animals.

There were no death or moribund animals during the test and no abnormal findings in all animals after dosing from the first day until the end of the test. Also there were no signs of dermal irritation or abnormalities found at necropsy.

Based on the results, the acute dermal LD50in rats for 1,1-dimethylurea was as follows:

Male rats:>2000 mg/kg b.w.

Female rats:>2000 mg/kg b.w.