Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1971
Report date:
1971

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
Conducted prior to the adoption of OECD test guideline.
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

Test material

Constituent 1
Chemical structure
Reference substance name:
[[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonic acid
EC Number:
239-931-4
EC Name:
[[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonic acid
Cas Number:
15827-60-8
Molecular formula:
C9H28N3O15P5
IUPAC Name:
[[(phosphonomethyl)imino]bis[ethane-2,1-diylnitrilobis(methylene)]]tetrakisphosphonic acid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: Males: 190-250 g. Females: 200-235 g.
- Weight at study initiation: No data
- 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

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: No data

Doses:
5010, 6310, 7940 and 10000 mg/kg bw
No. of animals per sex per dose:
5010 mg/kg bw : 2 male, 3 female; 6310 mg/kg bw: 3 male, 2 female; 7940 mg/kg bw: 2 male, 3 female; 10000 mg/kg bw:  3 male, 2 female.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: yes, animals that died during the test and surviving animals (killed seven days after dosing) were necropsied.  Viscera of test animals were observed macroscopically.  
- Other examinations performed: clinical signs
Statistics:
LD50 calculated by a modification of the method of E.J. de Beer (no further details).  Calculation not presented.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 7 180 mg/kg bw
Based on:
test mat.
95% CL:
>= 6 570 - <= 7 830
Remarks on result:
other: equivalent to 4164 mg active acid/kg bw
Mortality:
0, 2 (females), 3 (females) and 5 deaths at 5010, 6310, 7940 and 10000 mg/kg bw, respectively. Survival times were several hours to one day.
Clinical signs:
Toxic signs included reduced appetite and activity, slight lethargy (lasting two to seven days in survivors), rapidly increasing weakness, collapse and death.
Body weight:
Surviving female rats sustained weight loss in seven days. Males recovered initial weight loss and most showed weight gain.
Gross pathology:
In animals that died there was slight liver discolouration and acute gastrointestinal inflammation. Seven days after administration the viscera of surving animals appeared normal at macroscopic examination.
Other findings:
None reported.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study (reliability score 2) conducted prior to the adoption of OECD guidelines and GLP, the LD50 for DTPMP-H was 7180 mg/kg (previous reviewer comment: presumed equivalent to 4164 mg active acid/kg bw) in the rat.
Executive summary:

In an acute oral toxicity study (reliability score 2) conducted prior to the adoption of OECD guidelines and GLP, a single dose of DTPMP-H was administered to by oral gavage to Sprague-Dawley rats (mixed sex 5/dose). Doses of 5010, 6310, 7940 and 10000 mg/kg bw were tested. The animals were then observed for seven days, after which surviving animals were killed. All animals were examined macroscopically. There were 0, 2 (females), 3 (females) and 5 deaths at 5010, 6310, 7940 and 10000 mg/kg bw, respectively. Survival times were several hours to one day. Toxic signs included reduced appetite and activity, slight lethargy (lasting two to seven days in survivors), rapidly increasing weakness, collapse and death. Surviving female rats sustained weight loss in seven days. Males recovered initial weight loss and most showed weight gain. In animals that died there was slight liver discolouration and acute gastrointestinal inflammation. Seven days after administration the viscera of surviving animals appeared normal at macroscopic examination. The LD50 was calculated to be 7180 mg/kg bw (equivalent to 4164 mg active acid/kg bw).