Registration Dossier

Administrative data

Description of key information

Oral toxicity - LD50 (females): > 2000 mg/kg bw (OECD 423; GLP)
Dermal toxicity - LD50 (males/females): > 2000 mg/kg bw (OECD 402; GLP)

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2012-09-03 to 2012-09-18
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
(2001)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
(2002)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: CD / Crl: CD(SD)
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at start of administration: Approx. 8 weeks
- Weight at start of administration: 164 - 183 g
- Fasting period before study:
- Housing: During the 14-day observation period the animals were kept in groups of 3 animals 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 18, 2012

IN-LIFE DATES: From: August 21, 2012; To:September 18, 2012
Route of administration:
oral: gavage
Vehicle:
other: 0.8% aqueous hydroxypropylmethylcellulose
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 10 mL/kg bw
- Lot/batch no. (if required): 11 A 27-N27


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A limit test at one dose level of 2000 mg/kg bw was carried out on 6 female animals
Doses:
2000 mg/kg bw (limit test)
No. of animals per sex per dose:
6 female animals
Control animals:
no
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 surviving 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.

- 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.
Statistics:
No statistical analysis was performed as the method used is not intended to allow a calculation of a precise LD50 value.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: 24 hrs and 14 days
Mortality:
No death was recorded within the test period.
Clinical signs:
No clinical signs were noted.
Body weight:
All animals gained the expected weight throughout the whole study period.
Gross pathology:
No pathological changes were observed at necropsy.
Other findings:
- Histopathology:
No histopathology was carried out as no macroscopical findings were noted at autopsy.

Study report attachment:

LPT 28719 (Table 3 Bodyweights)

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

In an acute oral toxicity study, 6 female rats (CD/Crl: CD(SD) were given a single oral dose of Brassylci acid in 0.8% aqueous hydroxypropylmethylcellulose by gavage at a dose of 2000 mg/kg bw.

Animals were then observed for 14 days. There were no deaths and no treatment-related clinical signs, necropsy findings or changes in body weight during the study.

Oral LD50 Females = > 2000 mg/kg bw (Limit test with no mortalities)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study was the only study available and was assigned a Klimisch score of 1. The overall quality of the database is high.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
(1987)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Version / remarks:
(2008)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
(1998)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: CD/Crl: CD(SD)
Sex:
male/female
Details on test animals 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
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.
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.

Study report attachment:

LPT 28720 (Table 3 Bodyweights)

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)

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
The key study was the only study available and was assigned a Klimisch score of 1. The overall quality of the database is high.

Additional information

Acute inhalation toxicity is waived as the test substance has a very low vapor pressure and high melting point, so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.

Acute oral toxicity and acute dermal toxicity studies are available. Both studies had a Klimisch score of 1 and the results from both studies are acceptable to use in the human health risk assessment.


Justification for selection of acute toxicity – oral endpoint
Only 1 key study was available.

Justification for selection of acute toxicity – inhalation endpoint
The test substance has a very low vapor pressure and high melting point, so the potential for the generation of inhalable forms is low, also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalatory route will be unlikely to occur, and no acute inhalation test was performed.

Justification for selection of acute toxicity – dermal endpoint
Only 1 key study was available.

Justification for classification or non-classification

Based on the available information in the dossier, the substance tridecanedioic acid (CAS No. 505-52-2) does not need to be classified for acute toxiciy or for specific target organ toxicity - single exposure when the criteria outlined in Annex I of 1272/2008/EC are applied.