Phosphonic acid, P-(3,3,4,4,5,5,6,6,7,7,8,8,8-tridecafluorooctyl)-, sodium salt (1:1)

Endpoint summary

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:

Arrival of the Test Item: 16 June 2011 Date of Final Report: 10 October 2011

Reliability:

1 (reliable without restriction)

Qualifier:

according to guideline

Guideline:

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

Principles of method if other than guideline:

First Addendum to OECD Guidelines for Testing of Chemicals, Section 4, No. 423, ‘’Acute Oral Toxicity - Acute Toxic Class Method’’ adopted 17 December 2001 [3]

Commission Regulation (EC) No. 440/2008, L 142, Annex Part B, 30 May 2008 [4]

EPA Health Effects Test Guidelines, OPPTS 870.1000 ‘’Acute toxicity testing background’’, EPA 712-C-02-189, December 2002 [5]

EPA Health Effects Test Guidelines OPPTS 870.1000 ‘’Acute oral toxicity’’, EPA 712- C-02-190, December 2002 [6]

Ministry of Health and Welfare (MHW, Japan): Japanese Guidelines for Nonclinical Studies of Drugs Manual 1995, Yakuji-Nippo Co. Ltd., 1995 (unofficial translation) [7]

Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Guidelines for Preparation of Study Results, Acute Oral Toxicity Studies, Guideline 2-1-1. Notification 12 NohSan No. 8147, as partly revised in 16-Shouan-9260, on March 2005. English translation by IAI:ACIS on 17 October 2005 [8]

[3] OECD, 2001: Acute Oral Toxicity - Acute Toxic Class Method, OECD Guidelines for Testing of Chemicals 423, adopted 17 December 2001

[4] Commission Regulation (EC) No 440/2008, L 142, Annex Part B of 30 May 2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)

[5] EPA Health Effects Test Guidelines, OPPTS 870.1000 Acute Toxicity Testing Background, EPA 712-C-02-189, December 2002, United States, Environmental Protection Agency, Prevention, Pesticides and Toxic Substances (7101)

[6] EPA Health Effects Test Guidelines, OPPTS 870.1100 Acute Oral Toxicity, EPA 712-C-02-190, December 2002, United States, Environmental Protection Agency, Prevention, Pesticides and Toxic Substances (7101)

[7] Ministry of Health and Welfare (MHW, Japan): Japanese Guidelines for Nonclinical Studies of Drugs Manual 1995, Yakuji-Nippo Co. Ltd., 1995 (unofficial translation)

[8] Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Guidelines for Preparation of Study Results, Acute Oral Toxicity Studies, Guideline 2-1-1. Notification 12 NohSan No. 8147, as partly revised in 16-Shouan-9260, on March 2005. English translation by IAI:ACIS on 17 October 2005

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: 10 – 12 weeks old
- Weight at study initiation (on day of administration):
Animals no. 1 - 3, step 1: 168 - 173 g
Animals no. 4 - 6, step 2: 174 - 183 g
- Fasting period before study: Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.
- Housing: The animals were kept in groups in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 060411)
- Diet (e.g. ad libitum): Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1455)
- Water (e.g. ad libitum): Free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
- Acclimation period: at least 5 days
(Full barrier in an air-conditioned room)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Vehicle:

other: Aqua ad injectionem (sterile water, Berlin Chemie, lot no. 0195A191, expiry date: 04/2013)

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube. The test item was administered at a dose volume of 10 mL/kg body weight.

Doses:

The starting dose was selected to be 2000 mg/kg body weight. No compound-related mortality was recorded for any animal of step 1. Based on these results and according to the acute toxic class method regime, a second step was performed at the same dose. Compound-related mortality was recorded for one animal of step 2. Based on these results and according to the acute toxic class method regime no further testing was required.

No. of animals per sex per dose:

3 per step (2 steps) (6 in total)

Control animals:

no

Details on study design:

Observation Period: The surviving animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.

Weight Assessment: The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.

Clinical Examination: A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.

Cageside observations included changes in the skin and fur, eyes and mucous membranes. Also respiratory, circulatory, autonomic and central nervous systems and somatomotor activity and behaviour pattern were examined. Particular attention was directed to observations of tremor, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Pathology: The animal which died during the observation period was necropsied as soon as it was found dead. At the end of the observation period the surviving animals were sacrificed with an overdoseage of pentobarbital 208120; expiry date: 12/2013) at a dosage of approximately 8 mL/kg bw. All animals were subjected to gross necropsy. All gross pathological changes were recorded and in case of findings the tissues were preserved for possible histopathological evaluation.

Statistics:

N/A

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Based on:

test mat.

Clinical signs:

other: The test item showed acute oral toxicity characteristics after a single dose administration. For individual data see Table 2 of attached report - Clinical Signs - Individual Data. Based on these results and according to the acute toxic class method regim

Gross pathology:

Pathology: With the exception of acute injection of blood vessels in the abdominal region of the euthanised animals, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal (for individual data see Table 4 of attached report - Findings of the Necropsy - Individual Data).

See attahced study report

Interpretation of results:

Category 5 based on GHS criteria

Remarks:

Migrated information

Conclusions:

Under the conditions of the present study, a single oral application of the test item FHP-OHS to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity and mortality.

The median lethal dose of FHP-OHS after single oral administration to female rats, observed over a period of 14 days is:

LD50 cut-off (rat): 2500 mg/kg

In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC [11], the test item FHP-OHS has no obligatory labelling requirement for toxicity.

According to Annex 1 of Regulation (EC) 1272/2008 [13], the test item FHP-OHS has no obligatory labelling requirement for toxicity and is not classified.

According to OECD-GHS (Globally Harmonized Classification System) [12], the test item FHP-OHS has obligatory labelling requirement for toxicity and is classified into Category 5.

According to EPA Health Effects Test Guideline OPPTS 870.1000 [5], the test item FHP-OHS is classified into Category 3.

[5] EPA Health Effects Test Guidelines, OPPTS 870.1000 Acute Toxicity Testing Background, EPA 712-C-02-189, December 2002, United States, Environmental Protection Agency, Prevention, Pesticides and Toxic Substances (7101)

[11] Commission Directive 2001/59/EC adapting to technical progress for the 28th time Council Directive 67/548/EC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances, 06 August 2001 (Official Journal of the European Communities no. L 225/1, 21 August 2001)

[12] OECD-GHS - Globally Harmonized System of Classification and Labelling of Chemicals. Third revised edition, United Nations. New York / Geneva, July 2009

[13] Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. Official Journal of the European Communities, L 353, 31 December 2008

Executive summary:

Summary Results   Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was dissolved in the vehicle aqua ad injectionem (sterile water) at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.   All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.   Table 1: Results per Step     One animal treated with the test item at a dose of 2000 mg/kg was found dead 2 days after the administration. Before, the most relevant clinical findings in this animal were piloerection, half eyelid-closure and nasal discharge.   All remaining animals survived until the end of the study. The most relevant clinical finding in these animals was piloerection on the day of administration.   Throughout the 14-day observation period, the weight gain of the surviving animals was within the normal range of variation for this strain.   At necropsy, no macroscopic findings were observed in any animal of any step.   On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC [11], the substance should be: not classified and limit test   On the basis of the test results given below and in conformity with the criteria given in Annex 1 of Regulation (EC) 1272/2008 [13], the substance should be: not classified   On the basis of the test results given below and in conformity with the criteria given in OECD-GHS (Globally Harmonized System of Classification and Labelling of Chemicals) [12], the substance should be: classified in category 5   On the basis of the test results given below and in conformity with the criteria given in EPA Health Effects Test Guidelines, OPPTS 870.1000 ‘’Acute toxicity testing background’’, EPA 712-C-02-189, December 2002 [3], the substance should be: classified in category 3   LD50: 2500 mg/kg Species/strain: WISTAR Crl: WI(Han) rats Vehicle (moistening): aqua ad injectionem (sterile water) Number of animals: 5 male and 5 female Duration of exposure: 24 hours Method: OECD 423 [3]              Commission Regulation (EC) 440/2008 [4]              OPPTS 870.1000 [5]              OPPTS 870.1100 [6]              MHW () [7]              JMAFF [8]   Conclusions: Under the conditions of the present study, a single oral application of the test item FHP-OHS to rats at a dose of 2000 mg/kg body weight was associated with signs of toxicity and mortality. The median lethal dose of FHP-OHS after single oral administration to female rats, observed over a period of 14 days is: LD 50 cut-off (rat): 2500 mg/kg   In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC [11], the test item FHP-OHS has no obligatory labelling requirement for toxicity.   According to Annex 1 of Regulation (EC) 1272/2008 [13], the test item FHP-OHS has no obligatory labelling requirement for toxicity and is not classified.   According to OECD-GHS (Globally Harmonized Classification System) [12], the test item FHP-OHS has obligatory labelling requirement for toxicity and is classified into Category 5.   According to EPA Health Effects Test Guideline OPPTS 870.1000 [5], the test item FHP-OHS is classified into Category 3.   [3] OECD, 2001: Acute Oral Toxicity - Acute Toxic Class Method, OECD Guidelines for Testing of Chemicals 423, adopted 17 December 2001   [4] Commission Regulation (EC) No 440/2008, L 142, Annex Part B of 30 May 2008 laying down test methods pursuant to Regulation (EC) No. 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH)   [5] EPA Health Effects Test Guidelines, OPPTS 870.1000 Acute Toxicity Testing Background, EPA 712-C-02-189, December 2002, United States, Environmental Protection Agency, Prevention, Pesticides and Toxic Substances (7101)   [6] EPA Health Effects Test Guidelines, OPPTS 870.1100 Acute Oral Toxicity, EPA 712-C-02-190, December 2002, United States, Environmental Protection Agency, Prevention, Pesticides and Toxic Substances (7101)   [7] Ministry of Health and Welfare (MHW,): Japanese Guidelines for Nonclinical Studies of Drugs Manual 1995, Yakuji-Nippo Co. Ltd., 1995 (unofficial translation)   [8] Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), Guidelines for Preparation of Study Results, Acute Oral Toxicity Studies, Guideline 2-1-1. Notification 12 NohSan No. 8147, as partly revised in 16-Shouan-9260, on March 2005. English translation by IAI:ACIS on 17 October 2005   [11] Commission Directive 2001/59/EC adapting to technical progress for the 28th time Council Directive 67/548/EC on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances, 06 August 2001 (Official Journal of the European Communities no. L 225/1, 21 August 2001)   [12] OECD-GHS - Globally Harmonized System of Classification and Labelling of Chemicals. Third revised edition, United Nations./, July 2009   [13] Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. Official Journal of the European Communities, L 353, 31 December 2008

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 500 mg/kg bw

Additional information

Justification for selection of acute toxicity – oral endpoint
Only study available