Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20th April 2011 to 4th May 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: A GLP compliant study performed in line with appropriate guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2011

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
Details on test material:
- Physical state: off-white solid
- Storage condition of test material: room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories U.K. Ltd, Oxon., UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 221-258 g (female); 208-218 g (male)
- Housing: suspended solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent Diet ad libitum
- Water (e.g. ad libitum): mains water ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25ºC
- Humidity (%): 30-70%
- Air changes (per hr): at least fifteen per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
arachis oil
Remarks:
(the test material was moistened with arachis oil BP for application)
Details on dermal exposure:
TEST SITE
- % coverage: approximately 10% of total body surface area
- Type of wrap if used: self-adhesive bandage

REMOVAL OF TEST SUBSTANCE
- After the 24 hour contact period, the bandage was removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil to remove and residual test substance.
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for death or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: test sites were examined once daily for signs of primary irritation and scored according to the following Draize scale:

Erythema and Eschar formation
No erythema 0
Very slight erythema 1
Well-defined erythema 2
Moderate to severe erythema 3
Severe erythema and slight eschar formation 4

Oedema formation
No oedema 0
Very slight oedema 1
Slight oedema 2
Moderate oedema 3
Severe oedema 4

Bodyweights were recorded on days 0, 7 and 14.
Statistics:
Data evaluations included consideration of incidence and severity of all abnormalities including behavioural and clinical observations, gross lesions, bodyweight changes, mortality and any other toxicological effects. Mortality data was used to determine an estimated acute dermal lethal dose (LD50).

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived to the termination of the study.
Clinical signs:
Transient red/brown staining around the snout was noted in three males during the day of dosing.

Very slight erythema and haemorrhage of dermal capillaries was noted at the test sites of one male and one female the day after dosing. No other signs of dermal irritation were noted.
Body weight:
Animals showed expected gains in bodyweight over the study period except for one female which showed no gain in bodyweight during the first week but met expected bodyweight gain during the second week.
Gross pathology:
No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual bodyweights and weekly bodyweight changes

 Dose level (mg/kg bw)  Animal number and sex  Bodyweight (g) at day        Bodyweight change (g) during week   
     0  7  14  1  2
 2000  1-0 male  239  250  296  11  46
 2000  1-1 male  258  287  308  29  21
 2000  1-2 male  221  246  273  25  27
 2000  1-3 male  225  245  272  20  27
 2000  1-4 male  243  269  293  26  24
 2000  2-0 female  214  218  222  4  4
 2000  2-1 female  213  215  227  2  12
 2000  2-2 female  218  221  231  3  10
 2000  2-3 female  210  218  239  8  18
 2000  2-4 female  208  208  222  0  14

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the study, the acute dermal toxicity of the test substance gave an LD50 value of >2000 mg/kg bw.
Executive summary:

In a GLP compliant acute dermal toxicity study conducted in line with OECD Guideline 402 and EU Method B.3, the acute dermal toxicity of the test substance was investigated. The LD50of the substance was determined to be >2000 mg/kg bw.