Fatty acids, C6-24 and C6-24-unsatd., Me esters, distn. residues

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From August 17,2010 to September 07,2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Well described GLP compliant study conducted to recognized international test guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

yes

Remarks:

please see remarks below

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C6-24 and C6-24-unsatd., Me esters, distn. residues

EC Number:

310-083-8

EC Name:

Fatty acids, C6-24 and C6-24-unsatd., Me esters, distn. residues

Cas Number:

102242-52-4

Molecular formula:

UVCB substance, not univocal molecular formula available

IUPAC Name:

UVCB substance, no IUPAC name available, alternative EC chemical name: Fatty acids, C6-24 and C6-24-unsatd., Me esters, distn. Residues

Details on test material:

- Name of test material : Fatty acids, C6-24 and C6-24-unsatd., Me esters, distn. Residues
- Physical state: black , brown liquid
- Analytical purity: NO DATA
- Lot/batch No.: 070710
- Expiration date of the lot/batch:2011-05-30
- Storage condition of test material: room temperature
- Other:
The identity, composition and other characteristics which appropriately defined the batch from which the test item for this study was drawn, were determined by the Sponsor. Stability of the test item and methods of synthesis, fabrication or derivation are documented by the Sponsor.

Specific details on test material used for the study:

Fatty acids, C6-24 and C6-24-unsatd., Me esters, distn. residues- Physical state: black , brown semisolid- Analytical purity:100% - Storage condition of test material: room temperature- Solubility: < 10% in water, soluble in acetone, hexane and dichloromethane

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River
- Age at study initiation:7-9 weeks
- Weight at study initiation: Male 176-200 g , Female 176-192g
- Housing: The animals were housed individually in cages (dimensions 48 x 37.5 x 25 cm) with stainless steel grid tops and solid bottoms. Each cage was supplied with a water bottle and food hopper.
- Diet : Special Diets Services Limited, PO BOX 705 ; ad libitum.
- Water : ad libitum
- Acclimation period: From their arrival the animals were held as stock animals at Charles River, Edinburgh and they were acclimatised to the toxico logy accommodation for at least 2 weeks before treatment.
- Justification for selection : The rat was selected as the test model because of its ready availability and proven suitability in toxicology studies.

ENVIRONMENTAL CONDITIONS: The environment is monitored throughout the day and recordings are made every 15 min.
- Temperature (°C): 20°C
- Humidity (%): 50 to 70%.
- Air changes (per hr): 15 air changes per hour.
- Photoperiod: 12 h light/dark cycle
- Other:
Cages, cage racks and water bottles were changed weekly during the study. The floor was cleaned daily and the walls and ceiling were cleaned weekly with disinfectant solution.

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure:
- % coverage: 7 cm x 8 cm
- Type of wrap if used: The test item was then covered by a gauze patch, covered with a semi-occlusive tape and secured with a strip of non-irritating
occlusive tape wound round the trunk.

REMOVAL OF TEST SUBSTANCE
- Washing : yes, with water.

TEST MATERIAL
- Amount(s) applied : The administered doses were calculated on the basis of the body weights of the animals on the day of dosing.
- Concentration : A dose volume of 2.2 mL/kg was used and was based on the density of the test item (0.944 g/ml).
- Justification for selection: Dermal administration was selected for this study because it is a possible route of accidental human exposure and it allows hazard classification to be evaluated.

Duration of exposure:

single 24 h application.

Doses:

2000 mg/kg

No. of animals per sex per dose:

Dose volume: 2.2 ml/kg
5 Male
5 Female

Control animals:

yes, concurrent vehicle

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were examined for reaction to treatment 5 times on the day of dosing (Day 1) and daily thereafter until kill on Day 15.
-body weight : The body weight of each individual animal was recorded before dosing on Day 1 and on Days 8 and 15.
- Necropsy of survivors performed: yes
The necropsy consisted of an examination of the cranial, thoracic and abdominal organs and tissues in situ. Lesions were recorded in descriptive terms. Abnormal tissues were collected and preserved in 10% neutral buffered formalin. Carcasses were discarded after this procedure.

Statistics:

No formal statistical analysis was conducted.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: based on test item gravity (0.944 g/ml)

Mortality:

There were no unscheduled deaths during the observation period.

Clinical signs:

other: Clinical signs were restricted to test item residues, which were recorded in all animals after the removal of the dressings and which persisted in 2 of the rats throughout the observation period.

Gross pathology:

There were no abnormal findings noted in any of the females at necropsy. Two males displayed macroscopic abnormalities. The right testis of one rat was small, dark and flaccid and this was accompanied by a darkened epididymis. A few dark foci to the right middle lobe of the lung were also recorded in this animal. A second animal displayed enlarged mandibular lymph nodes. These findings are typical of background findings recorded in rats of this strain at these laboratories.

Any other information on results incl. tables

Protocol Deviation:

The males were not assigned to the study directly they were removed from their transport box, as the protocol stated. They were, however, randomly assigned to the study from stock and so this deviation was not considered to have had any impact on the integrity or outcome of the study. The daily mean humidity in the animal room was within the range of 40 to 70% that was stated in the protocol. However, there were several days when individual values were intermittently outside the range. The minimum recorded humidity was approximately 38% and the maximum was approximately 81%. Since there was no effect on the animals’ health, these deviations were not considered to have had any impact on the integrity or outcome of the study.

Method of killing:

Animals were euthanized by exposure to a rising concentration of carbon dioxide and major blood vessels were severed to exsanguinate.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The median lethal dermal dosage (LD50) for Fatty acids, C6-24 and C6-24 unsaturated, methyl esters, distillation residues in Sprague-Dawley rats was estimated to be greater than 2000 mg/kg.

Executive summary:

This study investigated the dermal toxicity potential of the test item, Fatty acids, C6-24 and C6-24 unsaturated, methyl esters, distillation residues, after a single administration to Sprague-Dawley rats. For the purposes of this report, the test item will be referred to as the distillation residues. Five males and 5 females received the distillation residues at a dose level of 2000 mg/kg. The test item was administered, as supplied, onto the dorsal trunk and covered with an occlusive patch for 24 h. The dose volume was 2.2 mL/kg, which was calculated on the basis of the density of the test item (0.944 g/mL). Animals were observed for signs of reaction to treatment 5 times on the day of dosing and once daily from Day 2 until the end of the observation period on Day 15. Body weights were recorded weekly and all animals were subjected to a necropsy examination. There were no systemic signs noted in any animal at any observation timepoint. Clinical signs were restricted to residual test item on the animals after removal of the dressings. This was seen in all animals. Body weight gain was considered to be acceptable for rats of this age and strain. Necropsy revealed no macroscopic abnormalities that were considered to be related to treatment.