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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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study was conducted to OECD guidelines and under GLP

Data source

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

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:
Heptan-2-one
EC Number:
203-767-1
EC Name:
Heptan-2-one
Cas Number:
110-43-0
Molecular formula:
C7H14O
IUPAC Name:
heptan-2-one
Constituent 2
Reference substance name:
Methyl n-Amyl Ketone
IUPAC Name:
Methyl n-Amyl Ketone
Details on test material:

Sponsor's identification Methyl n-Amyl Ketone
Description pale yellow liquid
Batch number TD-9024390
Purity 99.63%
Date received 01 November 2010
Expiry date 01 November 2011
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 U.K. 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 ithin 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 200g, and were eight to twelve eeks of age.
The weight variation did not exceed ± 20% of the mean weight for each
sex.


The animals were housed in suspended solid-floor polypropylene cages furnished with wood flakes.
The animals were housed individually during the 24-hour exposure period
and in groups of five, by sex, for the remainder of the study. Free access to main drinking
water and food (2014 Teklad Global Rodent diet supplied by Harla Laboratories U.K.
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 th study.


The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 t
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.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
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
treated with 2000 mg/kg BW of the test article. The calculated volume of test item, as received,
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. 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. The animals were returned to group housing for the remainder of the study period.

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing
and subsequently once daily for fourteen days.

After removal of the dressings and subsequently once daily for fourteen days, the test sites were
examined for evidence of primary irritation and scored according to the following scale
from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and procedures for Evaluating the Toxicity of Household Substances, National Academy of sciences, Washington DC p.31:
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:
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


A group of ten animals (five males and five females) was given a single,
24-hour, semi-occluded dermal application of the undiluted test item to intact skin 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.

Results and discussion

Preliminary study:
There were no deaths during the study. For clinical signs of toxicity. staining aroung the snout was noted in three males and two females two and four hours after dosing. No other signs of systemic toxicity were noted. Small superficial scattered scabs were noted at the test sites of two females. There were no other signs of dermal irritation noted. All animals showed expected gains in bodyweight over the study period and no abnormalities were noted at necropsy. 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.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
staining aroung the snout was noted in three males and two females two and four hours after dosing. Small superficial scattered scabs were noted at the test sites of two females. No other signs of systemic toxicity were noted.
Body weight:
All animals showed expected gains in bodyweight over the study period
Gross pathology:
No abnormalities were noted at necropsy

Applicant's summary and conclusion

Conclusions:
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.
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

A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of the undiluted test item to intact skin 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 during the study. Clinical observations included staining aroung the snout in three males and two females two and four hours after dosing. No other signs of systemic toxicity were noted. Small superficial scattered scabs were noted at the test sites of two females. There were no other signs of dermal irritation noted. All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy. 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.