Fatty acids, C18-unsatd., phosphates

Endpoint summary

Description of key information

Oral exposure

There is one good quality guideline compliant acute toxicity study via oral route (OECD 423 - Acute Toxic Class Method) conducted for the substance (van Sas, P.H.T., 2017). The purpose of the study was to evaluate the potential toxic effect of the test item PFA after single oral administration to rats. A limit dose of 2000 mg/kg body weight was used as starting dose. In this study the LD50 value of the substance in the female rats was estimated to be greater than 2000 mg/kg of body weight.

In the study of van Sas, P.H.T., 2017 three female rats were gavaged with undiluted test substance at a dose level of 2000 mg/kg bw. No mortalities were observed during the test. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy. The post exposure period was 14 days. All animals showed expected gains in bodyweight. No abnormalities were noted at necropsy. The acute median lethal dose (LD50) of the test item in female Wistar rat was estimated to be greater than 2000 mg/kg bodyweight.

As a conclusion, the results of the key study did not indicate this substance to be classified for acute toxicity via oral route.

 

Inhalation exposure

In accordance with column 2 of REACH Annex VIII, testing by the inhalation route is not needed as the substance is classified as corrosive to the skin. In addition, PPEs are in use during the use of the substance so there is no risk of exposure to the substance via inhalation route. The PPEs and risk management measures are demonstrated in the CSR section 9 and 10.

 

Dermal exposure

In accordance with column 2 of REACH Annex VIII the acute toxicity by dermal route is not needed as the substance is classified as corrosive to the skin. This is established in the study by van Sas (2017) described in CSR Section 5.4. Furthermore, The PPEs are worn to protect skin during the use of the substance. The risks for acute systemic effects via dermal route are adequately controlled with the risk management measures presented for long-term systemic effects (see CSR sections 9&10).

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:

28.06.2017-21.07.2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 0101891886
- Expiration date of the lot/batch: 02 November 2017

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: stable
- Solubility and stability of the test substance in the solvent/vehicle: Not indicated

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements.
The dosing formulations were kept at room temperature until dosing. The dosing formulations and vehicle were stirred until and during dosing.
Adjustment was made for specific gravity of the vehicle and test item. No correction was made for the purity/composition of the test item.
Any residual volumes were discarded.

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Females (if applicable) nulliparous and non-pregnant: no
- Age at study initiation: Young adult animals (approximately 8 weeks old)
- Weight at study initiation: 148 to 166 g
- Fasting period before study: overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing:On arrival and following assignment to the study, animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. These housing conditions were maintained unless deemed inappropriate by the Study Director and/or Clinical Veterinarian. The room(s) in which the animals were kept were documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.
- Diet (e.g. ad libitum): Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures. The feed was analyzed by the supplier for nutritional components and environmental contaminants. Results of the analysis were provided by the supplier and are on file at the Test Facility. It is considered that there were no known contaminants in the feed that would interfere with the objectives of the study.
- Water (e.g. ad libitum): Municipal tap-water was freely available to each animal via water bottles. Periodic analysis of the water was performed, and results of these analyses are on file at the Test Facility. It is considered that there were no known contaminants in the water that would interfere with the objectives of the study.
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C
- Humidity (%): 40 to 70%
- Air changes (per hr): Ten or greater air changes per hour with 100% fresh air (no air recirculation)
- Photoperiod (hrs dark / hrs light): 12-hour light/12-hour dark

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

VEHICLE
- Justification for choice of vehicle: Trial preparations were performed at the Test Facility to select the suitable vehicle and to establish a suitable formulation procedure. Trial preparation formulations were not used for dosing and were discarded after the assessment is complete. These trial preparations have a non-GLP status and were carried out in the quality assured environment of the Test Facility.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The dose levels were based on the OECD test guidelines and were selected from the series 5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight. The starting dose level should be the one that is likely to produce mortality in at least some of the animals and was selected based on available toxicity data of the test item.

Doses:

5 (lowest dose level), 50, 300 and 2000 (highest dose level) mg/kg body weight

No. of animals per sex per dose:

3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Postdose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. Animals were weighed individually on Day 1 (predose), 8 and 15. A fasted weight was recorded on the day of dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: clinical signs

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality was observed during the study.

Clinical signs:

other: Hunched posture and/or piloerection were observed for animals on Day 1.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

The oral LD50 value of Fatty acids, C18-unsatd., phosphates in Wistar rats was established to exceed 2000 mg/kg body weight.
According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.
Based on these results, Fatty acids, C18-unsatd., phosphates does not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Executive summary:

The objective of this study was to determine the potential toxicity of Fatty acids, C18-unsatd., phosphates, when given by oral gavage at a single dose to rats of a single sex at one or more defined doses to evaluate the potential reversibility of any findings.

The study was carried out in compliance with the guidelines described in:

•       OECD No.423 (2001) "Acute Oral Toxicity, Acute Toxic Class Method"

•       EC No 440/2008, part B: "Acute Oral Toxicity, Acute Toxic Class Method"

•       EPA, OPPTS 870.1100 (2002), "Acute Oral Toxicity"

•       JMAFF Guidelines (2000), including the most recent revisions.

Fatty acids, C18-unsatd., phosphates was administered by oral gavage to two consecutive groups of three female Wistar rats at 2000 mg/kg body weight.  Animals were subjected to daily observations and weekly determination of body weight.  Macroscopic examination was performed after terminal sacrifice (Day 15).

No mortality occurred.

Hunched posture and/or piloerection were observed for animals on Day 1.

The body weight gain shown by the animals over the study period was considered to be normal.

No abnormalities were found at macroscopic post mortem examination of the animals.

The oral LD50value of Fatty acids, C18-unsatd., phosphates in Wistar rats was established to exceed 2000 mg/kg body weight.

According to the OECD 423 test guideline, the LD50 cut-off value was considered to exceed 5000 mg/kg body weight.

Based on these results,Fatty acids, C18-unsatd., phosphatesdoes not have to be classified and has no obligatory labelling requirement for acute oral toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The available data for PFA indicate no potential for acute toxicity. Based on the oral LD50 value no classification is warranted for acute toxicity according to CLP Regulation 1272/2008.