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Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted at a GLP facility under OECD guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Butyronitrile
EC Number:
203-700-6
EC Name:
Butyronitrile
Cas Number:
109-74-0
Molecular formula:
C4H7N
IUPAC Name:
butyronitrile
Details on test material:
Sponsor's identification: N-butyronitrile
Description: clear colourless liquid
Batch number: TXTXOL
Purity: 99.891%
Date received: 30 September 2012
Expiry date: not supplied
Storage conditions: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
Five male and five female Wistar (RccHan™:WIST) strain rats were supplied by Harlan
Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to
cages. The females were nulliparous and non-pregnant. After an acclimatisation period
of at least five days the animals were selected at random and given a number unique
within the study by indelible ink-marking on the tail and a number written on a cage card.
At the start of the study the animals weighed at least 200 g, and were eight to twelve
weeks of age.
The animals were housed in suspended solid-floor polypropylene cages furnished with
woodflakes. The animals were housed individually during the 24-Hour exposure period
and in groups of up to four, by sex, for the remainder of the study. Free access to mains
drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan
Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking
water and bedding were routinely analysed and were considered not to contain any
contaminants that could reasonably be expected to affect the purpose or integrity of the
study.
The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to
70% respectively. Any occasional deviations from these targets were considered not to
have affected the purpose or integrity of the study. The rate of air exchange was at least
fifteen changes per hour and the lighting was controlled by a time switch to give twelve
hours continuous light (06:00 to 18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered
not to contain any contaminant of a level that might have affected the purpose or integrity
of the study.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
For each animal the calculated volume of test item was applied as evenly as possible to
an area of shorn skin (approximately 10% of the total body surface area) using a
graduated syringe. A piece of surgical gauze was placed over the treatment area and
semi-occluded with a piece of self-adhesive bandage. The animals were caged
individually for the 24-Hour exposure period and for the remainder of the test. Shortly
after dosing the dressings were examined to ensure that they were securely in place.
After the 24-Hour contact period the bandage was carefully removed and the treated skin
and surrounding hair wiped with cotton wool moistened with distilled water to remove any
residual test item.
Duration of exposure:
24 hours
Doses:
500, 1000 or 2000 mg/kg
No. of animals per sex per dose:
1 for the rangefinding study and 4 for the limit test.
Control animals:
no
Details on study design:
On the day before treatment the back and flanks of each animal were clipped free of hair. Using available information on the toxicity of the test item, a single group of animals was initially treated as follows:

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (ml/kg) Male/Female
======================================
500 50 10 1/1

In the absence of mortality at a dose level of 500 mg/kg, an additional group of animals was
treated as follows:

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (ml/kg) Male/Female
======================================
1000 0.778 1.27 1/1


In the absence of mortality at a dose level of 1000 mg/kg, an additional group of animals
was treated as follows:

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (ml/kg) Male/Female
======================================
2000 0.778 2.54 1/1

In the absence of mortality at a dose level of 2000 mg/kg, an additional group of animals
was treated as follows:

Dose Level Concentration Dose Volume Number of Rats
(mg/kg) (ml/kg) Male/Female
======================================
2000 0.778 2.54 1/1


A total of ten animals were therefore treated at a dose level of 2000 mg/kg in the study.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
None
Clinical signs:
Red/brown staining around the eyes or snout was noted in the male treated at a dose
level of 1000 mg/kg and three animals treated at a dose level of 2000 mg/kg. There
were no signs of systemic toxicity noted in the remaining animals
Body weight:
One animal treated at a dose level of 1000 mg/kg and five animals treated at a dose
level of 2000 mg/kg showed bodyweight loss during the first week but expected gain in
bodyweight during the second week. The remaining animals showed expected gains in
bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: OECD GHS
Conclusions:
The acute dermal median lethal dose (LDso) of the test item in the Wistar strain rat was
found to be greater than 2000 mg/kg bodyweight
Executive summary:

The study was performed to assess the acute dermal toxicity of the test item in the Wistar strain rat. The method was designed to be compatible with the following: OECD Guidelines for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) ; Method 83 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008. Initially, three groups, each of two animals (one male and one female), were given single, 24 hour, semi-occluded dermal applications of the test item to intact skin at dose levels of 500, 1000 or 2000 mg/kg bodyweight. Based on the results of the initial test a further group of eight animals (four males and four females) was similarly treated with the undiluted test item at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. There were no deaths. Red/brown staining around the eyes or snout was noted in the male treated at a dose level of 1000 mg/kg and three animals treated at a dose level of 2000 mg/kg. There were no signs of systemic toxicity noted in the remaining animals. Very slight erythema was noted at the test site of the female treated at a dose level of 500 mg/kg. There were no signs of dermal irritation noted in the remaining animals. One animal treated at a dose level of 1000 mg/kg and five animals treated at a dose level of 2000 mg/kg showed bodyweight loss during the first week but expected gain in bodyweight during the second week. The remaining animals showed expected gains in bodyweight over the study period. Necropsy. No abnormalities were noted at necropsy. Conclusion. The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg bodyweight.

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