Registration Dossier

Administrative data

Description of key information

Acute oral toxicity study (similar to OECD 401, Kr. 1): LD50 rat > 2000 mg/kg bw, limit test
Acute dermal toxicity study (similar to OECD 402, Kr. 1): LD50 rabbit > 2000 mg/kg bw, limit test
No study on acute inhalation toxicity is required since the substance is a liquid with very low vapour pressure at ambient temperature.

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:
from 3 March 1997 to 30 April 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
other: 40 CFR 798.1175
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: 3-5 months
- Weight at study initiation: 226-237 g (m) 245-256 g (f)
- Fasting period before study: 16-20 hours
- Housing: 5/sex/cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled but conditions not specified
- Humidity (%): no data
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: from 7 March 1997 to 21 March 1997
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
not applicable

MAXIMUM DOSE VOLUME APPLIED: 0.45 mL
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: 14 days
- Frequency of observations: at 1, 2 and 4 hours post-dosing then once daily for clinical signs and twice daily for mortality
- Frequency of weighing: immediately pre-test, weekly, at death or termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
Dyspnea was observed in two females on days 1 and 2 of the observation period.
Body weight:
No effect
Gross pathology:
No abnormalities.
Other findings:
None
Interpretation of results:
GHS criteria not met
Conclusions:
The oral LD50 is greater than 2000 mg/kg, with no mortality or significant clinical effects. No classification is required according to the criteria of EU Reg. 1272/2008 or the Directive 67/548/EEC.
Executive summary:

In a GLP-compliant acute oral study performed similarly to the OECD 401 guideline, Wistar rats (5 animals/sex) were dosed by gavage with a single dose of undiluted Triethyl Phosphonoacetate (purity of 98.4%) at 2000 mg/kg body weight. The rats were observed 1, 2 and 4 hours post-dose then once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pre-test, weekly, at death and at termination in the survivors. All animals were examined for gross pathology.

All animals survived the 2000 mg/kg bw oral dose. Dyspnea was observed in two females on days 1 and 2 of the observation period. Body weight changes and necropsy results were normal. It was concluded that the LD50 is greater than 2000 mg/kg bw.

Therefore under the test conditions, Triethyl Phosphonoacetate is not classified for acute oral toxicity according to the criteria of the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study as a GLP compliance and a Klimisch score 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:
from 3 March 1997 to 30 April 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
other: TSCA 40 CFR 798.1100
Deviations:
no
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Age at study initiation: ca. 2 months
- Weight at study initiation: 2.0-2.3 kg (m) 2.0-2.3 kg (f)
- Fasting period before study: none
- Housing: individual
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): controlled but conditions not specified
- Humidity (%): no data
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12:12

IN-LIFE DATES: from 20 March 1997 to 3 April 1997
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal of the trunk
- % coverage: 10 x 15 cm
- Type of wrap if used: the test item was applied on a surgical gauze. Gentle pressure was applied to the gauze to aid in the distribution of the test item over the preparation site. The torso was wrapped with plastic which was secured with non-irritating tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle washing with distilled water
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): between 3.5 and 4.1 mL depending on the weight of the rabbit
- Constant volume or concentration used: no

VEHICLE
not applicable, test item applied undiluted
Duration of exposure:
24 hours
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: 14 days
- Frequency of observations: at 1, 2 and 4 hours post-dosing then once daily for clinical signs and twice daily for mortality. Test sites scored for dermal irritation at 24 hours post-dose and days 7 and 14, using Darize scoring system.
- Frequency of weighing: immediately pre-test, weekly, at death or termination
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
Instances of diarrhoea and few faeces were observed in one animal on days 12 to 14 of the observation period.
Body weight:
No effect
Gross pathology:
No effect
Other findings:
None

No dermal reactions.

Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 was greater than 2000 mg/kg bw, with no mortality and no significant clinical findings. No classification is required according to the criteria of EU Reg. 1272/2008 or Directive 67/548/EEC.
Executive summary:

In a GLP-compliant acute dermal toxicity study performed similarly to the OECD 402 guideline, New Zealand White Rabbits (5 animals/sex) were dosed dermally with undiluted Triethyl Phosphonoacetate (purity of 98.4%) at 2000 mg/kg body weight. The test material was kept in contact with the skin for 24 hours with an occlusive dressing. Dermal responses were recorded at 24 hours post dose and on days 7 and 14. The rabbits were observed 1, 2 and 4 hours post-dose then once daily for 14 days for toxicity and pharmacological effects. The animals were observed twice daily for mortality. Body weights were recorded immediately pre-test, weekly, at death and at termination in the survivers. All animals were examined for gross pathology.

All animals survived the 2000 mg/kg bw dermal dose. Instances of diarrhoea and few faeces were observed in one animal on days 12 to 14 of the observation period. There were no dermal reactions. Body weight changes and necropsy results were normal. It was concluded that the LD50 is greater than 2000 mg/kg bw.

Therefore under the test conditions, Triethyl Phosphonoacetate is not classified for acute dermal toxicity according to the criteria of the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.

This study is considered as acceptable and satisfies the requirement for acute oral toxicity endpoint.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
The study as a GLP compliance and a Klimisch score 1

Additional information

Oral Toxicity

In the key study (1997) the LD50 for male and female rats dosed by gavage with a single dose of undiluted triethyl phosphono acetate was > 2000 mg/kg bw. There was no evidence of systemic toxicity. Only dyspnea was observed in two females on days 1 and 2.

Inhalation Toxicity

No study on acute inhalation toxicity is required since the substance has a low vapour pressure at ambient temperature. Therefore the inhalation route is not the most appropriate route to assess the acute toxicity of the submitted substance.

Dermal Toxicity

In the key study (1997), the dermal LD50 value in male and female rabbits treated by dermal application for 24h (occlusive dressing) to undiluted triethyl phosphono acetate was >2000 mg/kg bw. Only instances of diarrhoea and few faeces were observed in one animal on days 12 to 14.


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

Justification for selection of acute toxicity – inhalation endpoint
waiving based on scientifically reason

Justification for selection of acute toxicity – dermal endpoint
Only one study available

Justification for classification or non-classification

Self-classification:

Oral:

Based on the available data, as the LD50 rat is higher than 2000 mg/kg bw, triethyl phosphono acetate is therefore not classified for acute oral toxicity according to the criteria of the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.

Dermal:

Based on the available data, as the LD50 rabbit is higher than 2000 mg/kg bw,triethyl phosphono acetate is therefore not classified for acute dermal toxicity according to the criteria of the Regulation (EC) 1272/2008 (CLP) and the Directive 67/548/EEC.

Inhalation:

No study on acute inhalation toxicity is available or required.