Registration Dossier

Administrative data

Description of key information

SPE1415 gives a reliable oral LD50 value of > 2000 mg/kg in the rat. This result is consistent with the low toxicity observed in reliable oral studies on the aminomethyl phosphonate structual analogues, ATMP (acid) and DTPMP (acid). These analogues also demonstrate low toxicity in reliable acute dermal studies. Additional supporting data on another confidential analogue substance is discussed in Additional Information.

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
other: Wistar Han
Sex:
female
Route of administration:
oral: gavage
Vehicle:
water
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
1 female at 300 mg/kg and 5 females at 2000 mg/kg
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days.
Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: yes
Preliminary study:
One animal was dosed at 300 mg/kg and there was no mortality or clinical signs of systemic toxicity. Then a single animal was dosed at 2000 mg/kg and there was again no mortality or clinical signs of systemic toxicity. So a further 4 animals were dosed at 2000 mg/kg.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no mortalities
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance has an oral LD50 in the rat of >2000 mg/kg
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Exceeds data requirements. The key study on the substance is Klimisch 1 and other key studies are Klimisch 2.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available
Quality of whole database:
The acute inhalation study is waived in accordance with Annex VIII, 8.5.2 column 2 of the REACH regulation. Exposure of humans via inhalation is unlikely taking into account the low vapour pressure of the substance and the unlikely possibility of exposure to aerosols, particles or droplets of an inhalable size. Reliable acute toxicity studies have been provided by the oral and dermal dose routes.

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: 2e The study meets generally accepted scientific principles, but was not conducted in compliance with GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
Conducted prior to adoption of OECD test guidelines.
Deviations:
yes
Remarks:
Limited detail on test substance, methods and animals/conditions.
Principles of method if other than guideline:
Method: other: Insufficient detail to fully assess comparability with OECD guideline.
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: 1.8 to 2.0 kg
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data


IN-LIFE DATES: No data
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: No data
- Type of wrap if used: 'plastic strips'


REMOVAL OF TEST SUBSTANCE
- Washing (if done): No data
- Time after start of exposure: No data


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): No data
- Constant volume or concentration used: No data



Duration of exposure:
24 hours
Doses:
3160, 5010, 7940 and 7940 mg/kg bw
No. of animals per sex per dose:
One male or female animal per dose.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, and macroscopic examination of all animals.
Statistics:
None
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 7 940 mg/kg bw
Remarks on result:
other: equivalent to >4605 mg active acid/kg bw
Mortality:
No deaths occurred.
Clinical signs:
Clinical symptoms included reduced appetite and activity for 1-2 days. 
Body weight:
No adverse effects reported, although the summary table shows that there was no weight change in animals five days after treatment.
Gross pathology:
No adverse findings.
Other findings:
None
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute dermal toxicity study (reliability score 2), conducted prior to the adoption of OECD test guidelines and GLP, the LD50 for diethylenetriamine penta(methylene phosphonic acid) was >7940 mg/kg bw (presumed equivalent to >4605 mg active acid/kg bw) in the rabbit.
Executive summary:

In an acute dermal toxicity study (reliability score 2), conducted prior to the adoption of OECD test guidelines and GLP, diethylenetriamine penta(methylene phosphonic acid) was applied to the clipped, intact skin of four New Zealand white rabbits, under an occlusive dressing, for 24 hours. Animals were then observed for 14 days, and all animals were examined macroscopically. No animals died and the LD50 was concluded to be greater than 7940 mg/kg bw (equivalent to >4605 mg active acid/kg bw). Toxic signs included reduced appetite and activity for one to two days after treatment. There were no abnormal macroscopic findings.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
4 605 mg/kg bw
Quality of whole database:
Exceeds data requirements. The key studies are both Klimisch 2.

Additional information

Justification for classification or non-classification

The substance and its aminophosphonate analogues consistently demonstrate low toxicity in a number of reliable assays by both the oral and dermal routes. Therefore there is no justification for classification of the substance.