Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
03.08.1982 to 17.08.1982
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphosphonic acid, sodium salt
EC Number:
244-751-4
EC Name:
[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphosphonic acid, sodium salt
Cas Number:
22042-96-2
Molecular formula:
C9H28N3O15P5.xNa
IUPAC Name:
sodium hydrogen [10,10-dihydroxy-10-oxido-2,5,8-tris(phosphonomethyl)-2,5,8-triaza-10-phosphadec-1-yl]phosphonate
Constituent 2
Reference substance name:
[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphos phonic acid, sodium salt
IUPAC Name:
[[(phosphonomethyl)imino]bis[(ethylenenitrilo)bis(methylene)]]tetrakisphos phonic acid, sodium salt
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: A. Tuck and Sons Limited, Battlesbridge, Essex, UK.
- Age at study initiation: 6 to 8 weeks
- Weight at study initiation: Males: 221-235 g; Females: 202-234 g.
- Fasting period before study: No
- Housing: Individually (during exposure) or in groups of five in polypropylene cages.
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum of five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22± 3
- Humidity (%): 65-75
- Air changes (per hr): Approximately 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 03.08.1982 to 17.08.1982

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Dorsal, lateral and ventral regions.
- % coverage: No data
- Type of wrap if used: Elastic adhesive bandage backed with aluminium foil.


REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw
Duration of exposure:
24 hours
Doses:
10 ml/kg bw
No. of animals per sex per dose:
Five
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Skin responses were evaluated 0.5, 1, 2, 3, 4, and 5 hours after removal of the patch and residual test substance, and each day for 14 days.  Body weight was measured on days 0, 7, and 14
- Necropsy of survivors performed: yes
- Other examinations performed: Macroscopic examination.
Statistics:
Not required as no deaths occurred.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 10 mL/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
>= 5 838 mg/kg bw
Based on:
act. ingr.
Remarks:
active salt
Remarks on result:
other: equivalent to 4612 mg active acid/kg bw
Mortality:
No deaths.
Clinical signs:
Lethargy was observed in two animals (one male and one female) on the day of dosing.  From four hours after dosing, no abnormal symptoms observed in any animal. 
Body weight:
Body weight were within normal limits throughout the test period.
Gross pathology:
No abnormal findings.
Other findings:
None

Any other information on results incl. tables

Calculation of equivalent dose: Based on 

1) average specific gravity of DTPMP-7Na = 1.39 (email, I. Bartlett to R. Wildey, 09.04.2003), 

2) DTPMP-7Na composed of 42% active salt including minor components, remainder presumed to be water (derived from online data sheet).

An error in the study report: the clinical observations section reports that lethargy was observed in one male animal only.  Appendix I (Individual clinical observations) shows that this symptom was also observed in one female animal.

For purposes of comparison with other Group 3 results, 
5838 mg active salt/kg bw is equivalent to 4612 mg active acid (DTPMP, CAS 15827-60-8)/kg bw.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute dermal toxicity study, conducted according to a protocol comparable to OECD Test Guideline 402 and according to GLP, the LD50 for DTPMP-7Na was ≥10 ml/kg bw (equivalent to 5838 mg active salt/kg bw and 4612 mg active acid/kg bw) in rats.