Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
According to column 2 of REACH Annex VII, the study does not need to be conducted because an acute toxicity study by the dermal route is available for the test substance and does not indicate skin irritation up to 2 000 mg/kg body weight (limit dose test).
Cross-reference
Reason / purpose for cross-reference:
data waiving: supporting information
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
15 November 1991 - 29 November 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
Species tested was different from the preferred one and the number of animals used was higher than that specified in the Guideline.
GLP compliance:
yes (incl. QA statement)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: CAMM Research Lab Animals, Wayne, NJ; Hazleton Research Products, Denver, PA; Buckshire Corporation, Perkasie, PA.
- Females nulliparous and non-pregnant: Not specified.
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: Male: 2051.6 g (SD = 221.97 g); Female: 2135.0 g (SD = 266.17 g)
- Fasting period before study: not specified.
- Housing: Rabbits were housed individually in cages sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council. Waste material was removed twice weekly. Cages and feeders were sanitized every two weeks.
- Diet (e.g. ad libitum): Ad libitum. Purina Lab Rabbit Chow H.FR. Food was checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging and scattering.
- Water (e.g. ad libitum): Ad libitum. Drinking water (Fresh tap-water). Water was monitored for contaminants at periodic intervals according to Standard Operating Procedure PH-018.
- Acclimation period: the animals were acclimatized for at least 5 days before treatment.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20ºC (±3ºC)
- Humidity (%): 30 to 70%
- Air changes (per hr): Not specified
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark cycle.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: Not specified.
- Type of wrap if used: A square gauze patch was placed on the animals to cover the dosed area. The animals were wrapped with rubber dam and an elastic bandage to retard evaporation.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the skin sites were wiped with water and gauze.
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Concentration (if solution): N/A
- Constant volume or concentration used: yes
- For solids, paste formed: N/A
Duration of exposure:
24 h
Doses:
2000 mg/kg body weight
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: Observations were recorded daily through Day 14. Body weights were recorded at initiation and on Days 7 and 14.
- Necropsy of survivors performed: yes. At termination, gross pathological findings were recorded and reported.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality ocurred during the study.
Clinical signs:
other: No clinical signs were observed in any animal receiving the test chemical.
Gross pathology:
No visible lesions were observed in any animal at terminal necropsy.

Table 1. Summary of Clinical Observations. N-Ethyl-2 Nitratoethyl Nitramine

Clinical signs Sex Hours Days
24 2 3 4 5 6 7 8 9 10 11 12 13 14
No signs M 5 5 5 5 5 5 5 5 5 5 5 5 5 5
F 5 5 5 5 5 5 5 5 5 5 5 5 5 5

Table 2. Summary of mortality. N-Ethyl-2 Nitratoethyl Nitramine

Dose (mg/kg) Sex Nº of rabbits Days Total mortality
2 3 4 5 6 7 8 9 10 11 12 13 14
2000 M 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0/5
2000 F 5 0 0 0 0 0 0 0 0 0 0 0 0 0 0/5

Table 3. Summary of Body Weights (g). N-Ethyl-2 Nitratoethyl Nitramine

Animal Number Sex Initial Day 7 Final
5271 M 2034 2186 2327
5272 M 2138 2192 2309
5273 M 2361 2521 2681
5274 M 1911 2137 2278
5275 M 1814 1934 2095
x   2051.6 2194.0 2338.0
S.D.   211.97 210.86 212.87
N   5 5 5
5276 F 2340 2503 2613
5277 F 1866 1990 2084
5278 F 2444 2636 2755
5279 F 1865 1984 2115
5280 F 2160 2284 2396
x   2135.0 2279.4 2392.6
S.D.   266.17 295.04 296.74
N   5 5 5

Table 4. Necropsy Observations (Incidence Values). N-Ethyl-2 Nitratoethyl Nitramine

Observation

Interim Death

Incidence

Terminal Necropsy Incidence

No visible

lesions

M F M F
- - 5 5
Interpretation of results:
other: No category (CLP Regulation EC no. 1272/2008)
Conclusions:
The LD50 of the test item is higher than 2000 mg/kg body weight by dermal route in rabbits.

Executive summary:

In a dermal limit test (GLP study), one group of 10 New Zealand White rabbits (five males and five females) was exposed to the test substance at 2000 mg/kg for an exposure period of 24 h. Animals were observed for clinical signs and mortality once daily for fourteen days. No mortality and no clinical signs were observed in any animal receiving the test chemical. There were no apparent effects on mean body weight throughout the study. No visible lesions were observed in any animal at terminal necropsy. Based upon these observations, the estimated acute dermal LD50 (combined sexes) was determined to be greater than 2000 mg/kg.

Data source

Materials and methods

Results and discussion

Applicant's summary and conclusion

Categories Display