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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-10 to 2013-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
24 February 1987
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
31 May 2008
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate
EC Number:
261-879-6
EC Name:
Bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate
Cas Number:
59719-67-4
Molecular formula:
C24H46N4O6
IUPAC Name:
bis[2-[2-(1-methylethyl)-3-oxazolidinyl]ethyl] hexan-1,2-diylbiscarbamate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Toxi-Coop Zrt. 1103 Budapest, Cserkesz u. 90, Hungary
- Age at study initiation: Young adult rats
- Weight at study initiation: Male: 245 - 273 g, female: 204 - 215 g
- Housing: During acclimatisation: 3 animals/sex/cage During the study: animals were housed individually
- Diet (e.g. ad libitum): ssniff® SM R/M-Z+H complete diet produced by ssniff Spezialdiäten GmbH, D-59494 Soest, Germany
- Water (e.g. ad libitum): Tap water
- Acclimation period: 19 days

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 30 - 70 %
- Air changes: 8 - 12 exchanges per hour
- Photoperiod: 12 hrs dark / 12 hrs light (Artificial light, from 6 am. to 6 pm)

IN-LIFE DATES: From: 2012-09-27 To: 2012-10-31

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: Helianthi annui oleum raffinatum
Details on dermal exposure:
TEST SITE
- Area of exposure: back of the animals
- % coverage: 10
- Type of wrap if used: semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing: body temperature water
- Time after start of exposure: 24 hours

TEST MATERIAL:
- Concentration: 400 mg/mL in vehicle (Helianthi annui oleum raffinatum)

VEHICLE
- Amount(s) applied: 5 mL/kg bw
- Lot/batch no.: 19/4
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
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 clinical observations: Animals were observed individually 1 h and 5 h after dosing, and once each day for 14 days thereafter. Observations included the skin and fur, eyes and mucous membranes, and also respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
- Inspection for signs of morbidity and mortality were made twice daily.
- Frequency of weighing: The body weight of all animals were recorded on day 0 (shortly before the treatment), on day 7 and 15 (with a precision of 1 g).
- Necropsy of survivors performed: no
- Other examinations performed: gross pathology
Statistics:
not applicable

Results and discussion

Preliminary study:
There were no deaths in a preliminary study at 5, 50, 300 and 2000 mg/kg bw dose levels.
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortality occured.
Mortality:
No mortality occurred after the 24-hour dermal exposure to Incozol 4 in Crl:(WI)BR male and female rats during the study.
Clinical signs:
No behavioural changes or systemic toxic signs were noted during the study.
Dermal irritation symptom as erythema and other sign as wound were observed on the treatment site. The slight redness (score +1) appeared in all males and was detectable between Day 1 and Day 3. This symptom was also observed in all females and was detectable between Day 1 and Day 2. Wound was recorded in three males between Day 3 and Day 6.
Body weight:
Mean body weight development was within the normal range for male and female animals of this strain and age. The individual body weight of one female animal treated with 2000 mg/kg bw remained constant during the study period and no body weight gain was noted. The effect on body weight was considered to be test item-related as the animal did not regain the original body weight during the study. The body weight development was undisturbed in other females.
Gross pathology:
All animals survived until the scheduled necropsy on Day 15. No macroscopic alterations due to the systemic toxic effects of the test item were found.
Other findings:
No other findings.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In this acute dermal toxicity study with the test item Incozol 4, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats.
Executive summary:

An acute dermal toxicity study was performed with test item in Crl:(WI)BR rats, in compliance with OECD Guideline No. 402 and OPPTS 870.1200.

A limit test was carried out. A single group of male and female animals (n=5 animals/sex) was exposed to the test item at 2000 mg/kg bw by dermal route. The test item was applied in diluted form and left in contact with the skin for 24 hours, followed by a 14-day observation period. No mortality occurred after the 24-hour dermal exposure to the test item in Crl:(WI)BR male and female rats during the study. Neither male nor female animals treated with 2000 mg/kg bw of the test item showed behavioural changes and no systemic toxic signs were noted during the study. The test item caused dermal irritation symptoms as slight erythema in both sexes, between Day 1 and Day 3 in males and between Day 1 and Day 2 in females. Other dermal irritation symptom as wound was recorded in males between Day 3 and Day 6. Mean body weight development was within the normal range for male and female animals of this strain and age. The individual body weight of one female animal remained constant during the study period and no body weight gain was noted. The effect on body weight was considered to be test item related as the animal did not regain the original body weight during the study. The body weight development was undisturbed in other females. No macroscopic alterations of organs and tissues referred to the systemic toxic effect of the test item were seen during the necroscopy. In this acute dermal toxicity study with the test item, the obtained acute dermal LD50 value was greater than 2000 mg/kg bw in male and female Crl:(WI)BR rats. On the other hand, it is to be noted that the test item caused dermal irritation response at the site of administration.