Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
16 Sep 2014 to 21 July 2015
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2015
Report Date:
2015

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:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
ANIMALS AND ANIMAL HUSBANDRY- Five male and five female Wistar (RccHan: WIST) strain rats were supplied by Harlan Laboratories Ltd, Oxon, UK.- The animals were randomly allocated to cages on receipt.- Female animals were nulliparous and non-pregnant.- After an acclimatisation period of at least 5 days, animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and recording of the number on a cage card.- Animals weighed at least 200 g and were 8 to 12 weeks of age at the start of the study.- The weight variation did not exceed ± 20 % of the mean weight for each sex.- 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 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.- Temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively.- The rate of air exchange was at least fifteen changes per hour.- Lighting was controlled by a time switch to give 12 hours continuous light (06:00 to 18:00) and 12 hours darkness.- 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:
unchanged (no vehicle)
Details on dermal exposure:
PROCEDURE- 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.- 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.- After the 24 hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with suitable vehicle to remove any residual test item.- Animals were returned to group housing for the remainder of the study period.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
TEST ITEM FORMULATION AND EXPERIMENTAL PREPARATION- The test item was used as supplied.- Specific gravity was determined (1.079) and used to calculate the appropriate dose volume (1.86 mL/kg) for the required dose level.- Absorption of the test item was not determined.
Statistics:
- Data evaluations included the relationsip, if any, between exposure of the animal to the test item and the incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, body weight changes, mortality and other toxicological effects.- Using the mortality data obtained, and estimate of the acture dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No animal deaths took place.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
- Individual body weights and body weight changes are shown in Table 4 (attached).- Animals showed expected weight gain with the exception of one female, which showed body weight loss during the first week but expected gain in body weight during the second week.
Gross pathology:
- Individual necropsy findings are given in Table 5 (attached).- No abnormalities were noted at necropsy.
Other findings:
DERMAL REACTIONS- Individual dermal reactions are shown in Tables 2 and 3 (attached).- No signs of dermal irritation were observed.

Any other information on results incl. tables

- Individual clinical observations and mortality data are given in Table 1 (attached).

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
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 bw.
Executive summary:

GUIDELINE

OECD Guidelines for the Testing of Chemicals No 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No 440/2008.

METHODS

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 bw. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

RESULTS

Mortality: No animal deaths took place during the study.

Clinical observations: No signs of systemic toxicity were observed.

Dermal irritation: There were no signs of dermal irritation.

Body weight: Animals showed expected gains in body weight except for one female, which showed body weight loss during the first week but expected gain in body weight 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 2000 mg/kg bw.