Phosphonic acid, monoethyl ester, sodium salt (1:1)

Endpoint summary

Description of key information

Oral (OECD 401), rat: LD50: > 2000 mg/kg bw (limit test)

Inhalation (OECD 403), rat: LC50: > 5 mg/L (Read-across to Fosetyl-Al, CAS 39148-24-8, limit test)

Dermal (OECD 402), rat: LD50: > 2000 mg/kg bw (limit test)

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:

31 Oct - 14 Nov 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

(adopted 1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Version / remarks:

(adopted 1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Republique Francaise, Premier Ministre, Groupe Interministeriel Des Produits Chimiques, Paris Cedex, France

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar (AF) rats RJ:WI (IOPS AF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: R. Janvier, Le Genest St Isle, France
- Age at study initiation: 8 weeks
- Weight at study initiation: 261 - 281 g (males), 174 - 191 g (females)
- Fasting period before study: animals were fasted overnight until 3 - 4 hours after dosing
- Housing: individually in suspended stainless steel, wire mesh cages
- Diet: certified Rodent Pellet diet "M 20 controle" (Pietrement, Provins, France), ad libitum
- Water: filtered and softened water from the municipal water supply, ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15 (average, not monitored)
- Photoperiod (hrs dark / hrs light): (12 / 12)

IN-LIFE DATES: From: 31 Oct To 14 Nov 2000

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSE VOLUME APPLIED: 8.3 mL/kg bw

Doses:

2000 mg/kg bw (adjusted to purity)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: animals were observed 1 h after substance administration, at least once more on the Day of dosing and daily thereafter and individual body weights were determined periodically on Day -1 (prior to substance administration), 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: other: macroscopical examination of abdominal and thoracic cavities, major tisues and organs

Statistics:

For body weights, means and standard deviations were calculated for each sex.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: adjusted to purity

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: other: No clinical signs of toxicity were observed up to the end of the observation period.

Gross pathology:

Macroscopical examinations revealed no substance-related findings.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions chosen, no mortality occurred during the study period. The test substance did not induce any other adverse effects. The LD50 was concluded to be greater than 2000 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfill the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

24 Oct - 10 Nov 1997

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

(adopted in 1981)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Version / remarks:

2009

Deviations:

yes

Remarks:

Geometric standard deviation outside the recommended range (1.5-3.0)

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

THE DEPARTMENT OF HEALTH OF THE GOVERNMENT OF THE UNITED KINGDOM

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Sprague-Dawley Crl:CD ® BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: approx. 8 - 10 weeks
- Weight at study initiation: 271 - 301 g (males), 222 - 237 g (females)
- Housing: 5 animals of the same sex per cage in stainless steel lids, furnished with soft wood flakes (Dates and Ltd., Cheshire, UK)
- Diet: Rat and Mouse Expanded Diet No.1 (Special Diets Services Limited, Witham, Essex, UK), ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.4 µm

Geometric standard deviation (GSD):

0.33

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: cylindric exposure chamber
- Exposure chamber volume: 30 L
- Method of holding animals in test chamber: each rat was individually held in a tapered, polycarbonate restraining tube fitted onto a single tier of the exposure chamber and sealed by means of a rubber O-ring
- Source of air: compressed air (passed through a water trap and respiratory quality filters)
- System of generating particulates/aerosols: Wright's Dust Feed mechanism driven by a variable speed motor
- Method of particle size determination: cascade impactor (six impactor stages with stainless steel collection substrates (10, 6, 3.5, 1.6, 0.9 and 0.5 µm cut-off points) and a back up glass fibre filter housed in an aluminium sampler)
- Treatment of exhaust air: filtered
- Temperature and humidity: 20 ± 1°C and 46 ± 3%

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetrical analysis (chamber concentrations were determined at regular intervals during the exposure period using glass fibre filters (Gelman type A/E 25 mm) placed in filter holders temporarily sealed in a vacant port in the exposure chamber)
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: please refer to Table 1 under "Any other information on materials and methods incl. tables"
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.4 µm / 0.33 µm

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: based on the expected low toxicity of the test item, a nominal test concentration of 5 mg/L was selected in accordance to the limit concentration defined in OECD Guideline 403.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gravimetric

Duration of exposure:

4 h

Concentrations:

5 mg/L (nominal concentration)
5.11 mg/L (analytical concentration)

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed for clinical signs at hourly intervals during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and thereafter once daily. Individual body weights were recorded prior to treatment and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: behavioural observations

Statistics:

Mean values and standard errors were calculated from the examined parameters.

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.11 mg/L air (analytical)

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occured during the exposure and observation period.

Clinical signs:

other: During the exposure period, animals showed signs of wet fur (10/10), laboured respiration (5/5 males, 1/5 females) and a decreased respiration rate (3/5 males and females). Immediately after removal of the chamber, all animals revealed wet fur, hunched po

Body weight:

A possible reduction in body weight gain was observed in male animals during the first week of the 14 day observation period: body weight increased around 16 - 23 or 3 - 19 g during week 1 in male and female animals, respectively. Afterwards, increases around 26 - 57 or 4 - 18 g were determined during week 2 in males and females, respectively.

Gross pathology:

No abnormalities were observed in exposed animals except dark red foci on the lungs of 3/5 males and 1/5 females.

Table 2. Acute inhalation toxicity of Fosetyl Al.

 

Target concentration [mg/L air, analytical]	Toxicological results*	Duration of clinical signs	Time of death	Mortality (%)
Males
5.11	0/5/5	Day 0 - 4 (longest)	---	0
Females
5.11	0/5/5	Day 0 - 2	---	0
LC50 > 5.11 mg/L air

                                                                                           

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions chosen, no mortality was observed. Thus, the LC50 was determined to be greater than 5.11 mg/L air.

Reference 2

Endpoint:

acute toxicity: inhalation

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

refer to analogue justification provided in IUCLID section 13

Reason / purpose for cross-reference:

read-across source

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.11 mg/L air (analytical)

Based on:

other: read-across

Exp. duration:

4 h

Remarks on result:

other: Rat, RA source M178978-01-1

Conclusions:

Under the conditions chosen, no mortality was observed in the conducted study after inhalation exposure to the source substance aluminium tris(ethyl phosphonate). Thus, the LC50 was determined to be greater than 5.11 mg/L air.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1) from a reference substance with similar structure and intrinsic properties. Read-across is justified based on common metabolic fate, common structure and comparable intrinsic PC/ECO/TOX properties (please refer to the read-across justification in section 13). The selected study is thus sufficient to fulfill the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

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:

27 Mar - 12 Apr 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

(adopted 1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity: Fixed Dose Procedure)

Version / remarks:

2017

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

(adopted 1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

(adopted in August 1998)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Republique Francaise, Premier Ministre, Groupe Interministeriel Des Produits Chimiques, Paris Cedex, France

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar (AF) rats RJ:WI (IOPS HAN)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: R. Janvier, Le Genest St Isle, France
- Age at study initiation: 9 weeks
- Weight at study initiation: 348 - 369 g (males), 210 - 219 g (females)
- Housing: individually in suspended stainless steel, wire mesh cages
- Diet: certified Rodent Pellet diet "A04C (Usine d'Alimentation Rationnelle, Villemoisson-sur-Orge, France), ad libitum
- Water: filtered and softened water from the municipal water supply, ad libitum
- Acclimation period: 13 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 40 - 70
- Air changes (per hr): 10 - 15 (average, not monitored)
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: 14 Mar To 10 - 12 Apr 2001

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: clipped skin from the dorsum and flanks
- % coverage: 10%
- Type of wrap if used: The test material was held in contact with the skin with a 8-ply gauze dressing backed with an elastic wrap and a plastic tape. Removal and ingestion of the test article was prevented by placing an elastic wrap over the trunk and the test area.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): residual test material was removed with water
- Time after start of exposure: 24 h

TEST MATERIAL
- Concentration (if solution): 22.1% (aqueous solution)
- Constant volume or concentration used: yes (individual volumes were calculated according to the animals´weight on the day of dosing).

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: animals were observed 1 h after substance administration, at least once more on the Day of dosing and at least daily thereafter and individual body weights were determined periodically on Day -1 (prior to substance administration), 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: other: macroscopical examination of abdominal and thoracic cavities, major tisues and organs

Statistics:

Mean values were calculated for the body weight for each sex.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: other: No clinical signs of toxicity were observed up to the end of the observation period.

Gross pathology:

Macroscopical examinations revealed no substance-related findings.

Interpretation of results:

other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008

Conclusions:

Under the conditions chosen, no mortality was observed. The test substance did not induce any other adverse effects. The LD50 was determined to be greater than 2000 mg/kg bw/day.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Additional information

Acute toxicity

To assess acute toxicity of the test substance, data after oral and dermal exposure to the test substance are considered. No data are available on acute toxicity following inhalation for the test substance. However, there are reliable data on the analogue substance Fosetyl-Al (CAS 39148-24-8) available, which are considered suitable for read-across.

For details on the read-across approach, please refer to the analogue justification (section 13 of the technical dossier).

 

Acute toxicity: oral

The acute oral toxicity of the test substance was determined according to OECD Guideline 401 and in compliance with GLP (M-201622-01-1). Five Wistar rats per sex were administered to a single dose of 2000 mg/kg bw/day via gavage. No mortality occurred during the study period and no clinical signs of toxicity were observed until the end of the 15-day observation period. Moreover, body weight development appeared normal during the study. Further, necropsy did not reveal any specific pathological findings. Thus, a LD50 value > 2000 mg/kg bw/day was derived.

Acute toxicity: inhalation

Toxicity of the read-across substance Fosetyl-Al after acute inhalation was determined in a GLP-compliant study performed according to OECD Guideline 403 (M-178978-01-1). Five male and 5 female Sprague-Dawley rats were exposed for 4 hours to 5.11 mg/mL (analytical) dust in a nose-only exposure system. No mortality was observed during the study period. Clinical signs of toxicity including respiratory abnormalities like decreased respiratory rate and labored or noisy respiration were observed in several animals of both genders which resolved in all animals latest 5 days after exposure. Gross necropsy revealed dark red foci on the lungs of 3/5 males and 1/5 females. The mean median diameter of the inhaled fraction of 2.4 ± 0.33 µm indicates accumulation in the trachea-bronchial or pulmonary region of the respiratory tract (ECHA 2012). However, as respiratory symptoms were fully reversible latest within 5 days, permanent deposition of Fosetyl-Al remains unlikely due to either absorption of the particles and/or clearance mechanisms. As no mortality occurred in either sex after exposure to the limit dose of 5 mg/L (nominal), a LC50 of > 5.11 mg/L air (analytical) was defined. 

 

Acute toxicity: dermal

A GLP-conform acute dermal toxicity study was performed according to OECD Guideline 402 (M-203712-01-1). A limit dose of 2000 mg/kg bw/day were topically applied for 24 h to the clipped skin of 5 male and female Wistar rats under occlusive dressing. Neither mortality nor clinical signs of toxicity were observed until the end of the 15-day observation period. In addition, body weight gain was not affected in test animals. Further, macroscopical examinations did not reveal abnormalities. Thus, the dermal LD50 value is > 2000 mg/kg bw/day.

 

In conclusion, the test substance is not expected to induce acute toxicity following oral or dermal exposure. Moreover, based on the analogue substance Fosetyl-Al, low hazardous potential is expected for the test substance following inhalation. In addition, based on the physico-chemical properties of the test substance, exposure of humans via inhalation is unlikely.

Justification for classification or non-classification

The available data on acute toxicity do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.