Fatty acids, C16-18 and C18-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 July 30,2010 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:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Fatty acids, C16-18 and C18-unsatd., Me esters, distn. residues

EC Number:

271-692-1

EC Name:

Fatty acids, C16-18 and C18-unsatd., Me esters, distn. residues

Cas Number:

68604-41-1

Molecular formula:

UVCB substance, not univocal molecular formula available

IUPAC Name:

UVCB substance. No IUPAC name available, alternative EC chemical name: Fatty acids, C16-18 and C18-unsatd., Me esters, distn. residues The registered substance is the residue resulting from the distillation of C16-18 and C18 unsatd. fatty acids methyl esters sources

Details on test material:

- Name of test material :Fatty acids, C16-18 and C-18-unsaturated, methyl esters, distillation residues- Physical state: black , brown liquid- Analytical purity: NO DATA- Storage condition of test material: room temperature- Density: 0.92 g/mL at 20°C.

Specific details on test material used for the study:

- Name of test material :Fatty acids, C16-18 and C-18-unsaturated, methyl esters, distillation residues- Physical state: black , brown liquid- Analytical purity: NO DATA- Storage condition of test material: room temperature- Density: 0.92 g/mL at 20°C.

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- Study location: The study was conducted in room P39 of the toxicology accommodation at Charles River- Age at study initiation:7-9 weeks- Weight at study initiation: Male 176-200 g , Female 202 to 249 g- 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- Time of exposure: one single application for 24 hrs- Area of exposure: Trunk- % 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-irritatingocclusive 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/kg5 Male5 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 thereaf ter 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: yesThe 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

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 (0.92 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. Three males displayed macroscopic abnormalities. Reddening of all lobes of the lungs was seen in one animal, darkening of all lobes of the liver was recorded in a second and oneanimal displayed enlarged mandibular lymph nodes and dark foci to all lobes of the lungs. 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 animals 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 euthanised 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 informationCriteria used for interpretation of results: EU

Conclusions:

Under the conditions of the study, the median lethal dermal dosage (LD50) for Fatty acids, C16-18 and C18-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, C16-18 and C18-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 (0.92 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 anecropsy 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.