Pentapotassium ({[(hydroxyphosphinato)methyl](phosphonatomethyl)nitroryl}methyl)phosphonate

Endpoint summary

Description of key information

An acute oral toxicity study, conducted according to a standard acute toxicity method and in compliance with GLP, concluded an LD50 value of ≥5000 mg/kg bw/day based on no deaths up to the highest dose tested (RBM 1991a).

An acute dermal toxicity study, conducted according to a standard acute toxicity method and in compliance with GLP, concluded an LD50 value of ≥2000 mg/kg bw/day based on no deaths up to the highest dose tested (RBM, 1991b).

There is no inhalation study available, however, since oral and dermal route studies are available, the inhalation endpoint is waived.

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:

22 January 1991 - 05 February 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

other: ECC guideline - VI Amendment, Annex V, Directive 84/449/EEC

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia S.p.A., Via Indipendenza, 11, 22050 - CALCO (Como)
- Age at study initiation: ca. 7-9 weeks
- Weight at study initiation: 225-250 grams (males), 200-225 grams (females)
- Fasting period before study: 16 hours (Volume of dosing was based on day 1 bodyweight. Feed was returned to rats three hours after the test article administration).
- Housing: 5 animals/sex/cage in air-conditioned rooms, in grill cages with stainless steel feeders.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): ca. 20 / hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
Just before the treatment of the animals a weighed amount of the test article was dissolved with the suitable volume of deionized water.

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg

Doses:

5000 mg/kg

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Observations took place at 30 minutes, 2, 4 and 6 hours on the first day after the administration and then twice a day up to the termination of the observation period. Body weights were taken once pre-trial and on days 1, 3, 8 and 14. On day 1 the animals were weighed after a 16 hour fasting.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Histological examination was not performed as no macroscopic findings emerged from necropsy.

Statistics:

The LD50 calculation was not possible.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 5 000 mg/kg bw

Based on:

dissolved

Remarks on result:

other: No adverse effects observed

Mortality:

There were no deaths.

Clinical signs:

Hypoactivity, shallow breathing, piloerection and hunched posture were the main clinical signs observed starting from 30 minutes and lasting up to 2 days after the test article administration. Recovery of all treated animals was achieved 3 days after treatment.

Body weight:

The body weight gain of all the treated animals was considered within normal limits for rats of this strain and age (except for one female rat which showed a slight decrease in body weight gain only at the day 3 weighing).

Gross pathology:

No changes were noted in any of the necropsied animals.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An acute oral toxicity study, conducted according to a standard acute toxicity method and in compliance with GLP, concluded an LD50 value of ≥5000 mg/kg bw/day based on no adverse effects.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Quality of whole database:

Klimisch score of 1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

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 November - 12 December 1990

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Information lacking on whether the exposure was occlusive or semi-occlusive.

Qualifier:

according to guideline

Guideline:

other: EEC guidelines - VI Amendment, Annex V, Directive 84/449/EEC

Deviations:

yes

Remarks:

Lacking information on whether the exposure was occlusive or semi-occlusive.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Italia S.p.A., Via Indipendenza, 11, 22050 - CALCO (Como)
- Age at study initiation: ca. 7-9 weeks
- Weight at study initiation: Males: 225 - 250 grams. Females: 200 - 225 grams
- Housing: 1 animal/cage in air conditioned rooms. Grill cages with stainless steel feeder.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: Minimum of 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2 °C
- Humidity (%): 55 +/- 10 %
- Air changes (per hr): 20 / hour
- Photoperiod (hrs dark / hrs light): 12 hours dark / 12 hours light

Type of coverage:

not specified

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal and ventral area of the trunk of the test animals.
- % coverage: 10%
- Type of wrap if used: Not specified. Test report states that the treated area was covered with a porous gauze dressing fixed to the skin with tape and further covered in a 'suitable manner' to ensure that the animals could not ingest test material.

REMOVAL OF TEST SUBSTANCE
- Washing: At the end of the exposure period the test substance was wiped off.
- Time after start of exposure: 24 hours.

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw

Duration of exposure:

Single administration - 24 hour exposure

Doses:

2000 mg/kg

No. of animals per sex per dose:

5 males, 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: The animals were observed on exposure day at 30 minutes, 2, 4 and 6 hours and on the following 14 days twice per day (early in the morning and late in the afternoon. Body weights were taken once pre-trial, on the administration day and on days 8 and 15.

- Necropsy of survivors performed: yes

- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: Since no changes were found at necropsy, histological examination was not performed.

Statistics:

Since no mortality occurred at the limit dose of 2000 mg/kg, the LD50 was not calculated.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No adverse effects observed

Mortality:

No mortality occurred in the treated animals.

Clinical signs:

The rats did not show any clinical signs or change in behaviour and no reaction was observed on the application site.

Body weight:

Body weight gain of all rats was considered to be within normal limits for animals of this strain and age.

Gross pathology:

No changes were observed in the animals killed at the end of the study.

Other findings:

None reported.

Interpretation of results:

GHS criteria not met

Conclusions:

An acute dermal toxicity study, conducted according to a standard acute toxicity method and in compliance with GLP, concluded an LD50 value of ≥2000 mg/kg bw/day based on no adverse effects observed.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Klimisch score of 2.

Additional information

The available studies were reliable and therefore fulfilled the criteria for selection as key. The test substance for both key studies comprised of 38% salt and 27% active acid at pH 10.

In an acute oral toxicity study, ATMP-N-oxide-5K was administered to ten Sprague-Dawley rats in a single dose by oral gavage with a recovery period for 14 days. The dose was 5000 mg/kg. Clinical signs included hypoactivity, shallow breathing, piloerection and hunched posture starting 30 minutes after administration and lasting up to 2 days after the test article administration. Recovery of all treated animals was achieved 3 days after treatment. An LD50 was concluded to be ≥5000 mg/kg bw/day based on no deaths up to the highest dose tested (RBM 1991a).

In an acute dermal toxicity study, ATMP-N-oxide-5K was administered to ten Sprague-Dawley rats in a single dermal application of 2000 mg/kg. It was concluded that LD50 is ≥2000 mg/kg bw/day based on no deaths up to the highest dose tested (RBM, 1991b).

Acute oral and dermal toxicity data for ATMP-H have been included to support read-across within the ATMP and ATMP-N-Oxide Category. Therefore, these data have not been discussed in detail in this endpoint summary.

In a well-conducted acute oral study with ATMP-H, conducted according to a protocol similar to the now-deleted OECD Test Guideline 401, but not to GLP, an LD50 of 2910 mg/kg bw was determined for ATMP-H in the rat (Younger Laboratories, 1967a).

In a well-conducted acute dermal study with ATMP-H, conducted according to a protocol similar to OECD Test Guideline 402, but not in compliance with GLP, a dermal LD50 of >6310 mg/kg bw was determined for ATMP-H in the rabbit (Younger Laboratories, 1967b).

Justification for classification or non-classification

Based on the available data, no classification for acute toxicity is required for acute toxicity for ATMP-N-oxide-5K in accordance with Regulation (EC) No 1272/2008.