Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-09-03 to 2012-09-17
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Tridecanedioic acid
EC Number:
208-011-4
EC Name:
Tridecanedioic acid
Cas Number:
505-52-2
Molecular formula:
C13H24O4
IUPAC Name:
tridecanedioic acid
Constituent 2
Reference substance name:
Brassylic acid
IUPAC Name:
Brassylic acid
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Brassylic acid/Tridecanedioic acid
- Physical state: White powder
- Analytical purity: 99.42 %
- Lot/batch No.:3311050098 of 22 August 2011
- Expiration date of the lot/batch:27 Jun 2013
- Storage condition of test material: At room temperature

Test animals

Species:
rat
Strain:
other: CD/Crl: CD(SD)
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories Research Models and Services, 97633 Sulzfeld Germany
- Age at dosing : approximately 8 weeks (males/females)
- Weight at dosing: Males: 216 - 226 g; Females: 205 - 216 g
- Fasting period before study:
- Housing: Animals were kept singly in MAKROLON cages (type III plus). Granulated textured wood was used as bedding material for the cages.
- Diet:Commercial diet, ssniff® R/M-H V1534 (Certificates of analysis provided) ; discontinued approx. 16 hours before administration
- Water: tap water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 12 to 18-fold air change per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light (about 150 lux at approx. 1.50 m room height)

IN-LIFE DATES: From: August 21, 2012; To: September 17, 2012

Administration / exposure

Type of coverage:
occlusive
Vehicle:
other: Aqua ad iniectabilia (water for injection)
Details on dermal exposure:
TEST SITE
- Area of exposure: shaved intact dorsal skin; the site was situated on the animal's back between the fore and hind extremities
- % coverage: 5 cm x 6 cm, approx. 1/10 of body surface
- Type of wrap if used: Eight layers of gauze covered with a plastic sheet and secured with adhesive plaster strips (Omniplast (P. HARTMANN AG), Germany)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing
- Time after start of exposure: the occlusive test patch was removed after 24 hrs

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2 g Brassylic acid were moistened with 1 g aqua ad iniectabilia; 3 g/kg was applied per animal

VEHICLE
- Lot/batch no. (if required): 121378141 (B. Braun Melsungen AG, 34212 Melsungen, Germany )
Duration of exposure:
24 hrs
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
10 animals (5 males and 5 females)
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations were performed before and immediately, 5, 15, 30 and 60 min, as well as 3, 6 and 24 hours after administration. All animals were observed for a period of 14 days. Individual body weights were recorded before administration of the testsubstance and thereafter in weekly intervals up to the end of the study. Observations on mortality were made at least once daily.

- Necropsy of survivors performed: yes (all animals)

- Other examinations performed: changes of skin and fur, eyes and mucous membranes, respiratory and the circulatory,autonomic and central nervous system and somatomotor activity as well as behaviour pattern were observed at least once a day until all symptoms subsided, thereafter each working day. Any tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma were also noted.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 24 hrs and 14 days
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical signs of toxicity.
Body weight:
There was no treatment-related effects on bodyweight.
Gross pathology:
The macroscopic examination did not reveal any changes.
Other findings:
- Histopathology:
No histopathology was carried out as no macroscopical findings were noted at necropsy

- Other observations:
No skin reactions were observed at the application site.
No influence on animal behaviour was noted.

Any other information on results incl. tables

Study report attachment:

LPT 28720 (Table 3 Bodyweights)

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this acute dermal toxicity study in rats (limit test), the LD 50 (males/females) for Brassylic acid was > 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study, groups of young adult CD/Crl: CD(SD) rats (5/sex) were dermally exposed (occlusive) to Brassylic acid in water for injection for 24 hours to 1/10 of the body surface at a dose of 2000 mg/kg bw. Animals then were observed for 14 days.

There were no deaths during the study and no treatment related clinical signs, necropsy findings, changes in body weight or animal behaviour were observed. No skin reactions were observed at the application site.

Dermal LD50 Male/Female = > 2000 mg/kg bw (Limit test, no mortalities)