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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:
2 (reliable with restrictions)

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)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Details on test material:
Physical appearance: solid
Expiry date : June 1995
Storage: room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Five male and five female Wistar (RccHanÔ: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 acclimatization 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 analyzed 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 (06:00-18:00) 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
Duration of exposure:
24-hour contact period
Doses:
2000 mg/kg
No. of animals per sex per dose:
five (5) male and five (5) female
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 group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.
The appropriate amount of test item, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). 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 ½, 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 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.

Any other skin reactions, if present were also recorded.

Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
One female showed expected gain in bodyweight during the first week but body weight loss during the second week. Two females showed bodyweight loss or no gain in body weight during the first week with expected gain in bodyweight during the second week. Remaining animals showed expected gains in body weight during the study.
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
Orange coloured staining, not preventing evaluation of skin responses, was noted at the test sites of all animals during the study.
Physical damage caused on bandage removal was noted at the test site of one male 1 to 10 days after dosing. Small superficial scattered scabs and glossy skin were also noted at this test site 11 and 12 days after dosing with glossy skin persisting 13 and 14 days after dosing.
There were no signs of dermal irritation noted at the test sites of the remaining nine animals.

Any other information on results incl. tables

Individual Dermal Reactions - Males

 Dose level mg/kg     Animal number and sex     Observation                             Effects noted after initation of exposure (days)               
 1  4  5  6  7  8  9  10  11  12  13  14
2000                                                              1 -0 male  Erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Other  STAPd  STAPd  STAPd  STAPd  STAPd  Pd  Pd  Pd  Pd  Pd  SsG SsG   G
       1 -1 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       1 -2 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA   STA  STA  STA  STA  STA  STA  0  0  0  0  0  0
       1 -3 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       1 -4 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0 0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  STA  STA  STA  0  0  0  0  0

Individual Dermal reactions - females                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  

0: no reactions; STA: Orange coloured staining; Pd: Physical damage caused on bandage removal; Ss: Small superficial scattered scabs; G: Glossy skin.

Individual Dermal reactions - females

    Dose level mg/kg    animal number and sex     observation                      Effects noted after initiation of exposure (days)                   
 1  2  3  4  5  6  7  8  9  10  11  12  13  14
                                                   2 -0 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       2 -1 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0
       2 -2 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  STA  0  0  0  0  0  0  0
       2 -3 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       2 -4 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  STA  STA  0  0  0  0  0  0

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Remarks:
Classification criteria according to the CLP Regulation 1272/2008 and its amendments
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 body weight
Executive summary:

A group of ten animals (five males and five females) was given a single, 24 hours, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy (No abnormalities were noted at necropsy).

The observation on mortality showed that there were no deaths. Clinical observations showed no signs of systemic toxicity. Observation on dermal irritation showed a physical damage caused on bandage removal, small superficial scattered scabs and glossy skin were confined to the test site of one male. There were no signs of dermal irritation noted at the test sites of the remaining nine animals. Observations in body weight gave as a result that one female showed expected gain in bodyweight during the first week but body weight loss during the second week. Two females showed bodyweight loss or no gain in body weight during the first week with expected gain in bodyweight during the second week. Remaining animals showed expected gains in body weight during the study.