Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
The study was performed between 31 January 2013 and 14 February 2013.
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
Sponsor's identification : Sodium Glucoheptonate (EC 250-480-2)
Description : dark brown liquid
Lot number : 921000100
Purity : 49.5%
Date received : 09 February 2012
Expiry date : 09 February 2015
Storage conditions : room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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 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 woodflakes. 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 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.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
On the day before treatment the back and flanks of each animal were clipped free of hair. 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.

REMOVAL OF TEST SUBSTANCE
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.

TEST MATERIAL
For the purpose of the study, the test item was used as supplied. The specific gravity was determined and used to calculate the appropriate dose volume for the required dose level. The dose level was adjusted to account for the purity of the test item (49.5%).
Duration of exposure:
24 hours
Doses:
2000 mg/kg active ingredient (4041 mg/kg bodyweight)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- The following were investigated: clinical observations, mortality, bodyweight changes and findings at necropsy.

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
4 040 mg/kg bw
Based on:
test mat.
Remarks on result:
other: equivalent to 2000 mg/kg active ingredient
Mortality:
There were no deaths throughout the study.
Clinical signs:
Red/brown staining around the right eye was noted in one male. There were no other signs of systemic toxicity noted.
Body weight:
Animals showed expected gains in bodyweight over the study period, except for one female which showed expected gain in bodyweight during the first week but bodyweight loss during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Dermal reactions:

Signs of dermal irritation noted at the test site of one female five and six days after dosing were very slight erythema and small superficial scattered scabs with glossy skin noted at this test site seven days after dosing. There were no signs of dermal irritation noted at the test sites of the remaining animals.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 4041 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight). Due to the results of the study, the substance is not classified according to either the DSD or CLP.
Executive summary:

Introduction: 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 B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

Method: 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 4041 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight). Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

Mortality: There were no deaths.

Clinical Observations: Red/brown staining around the right eye was noted in one male. There were no other signs of systemic toxicity noted.

Dermal Irritation: Signs of dermal irritation noted at the test site of one female were very slight erythema, small superficial scattered scabs and glossy skin. There were no signs of dermal irritation noted in the remaining animals.

Bodyweight: Animals showed expected gains in bodyweight over the study period, except for one female which showed expected gain in bodyweight during the first week but bodyweight loss during the second week.

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 4041 mg/kg bodyweight (equivalent to 2000 mg active ingredient/kg bodyweight).