Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1989-08-15 until 1989-08-29
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: scientifically acceptable and well documented
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1990
Report Date:
1990

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
NA
GLP compliance:
yes
Test type:
standard acute method

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Composition of test material, percentage of components: 64.7% water, 32.6% Tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate, 1.3% Trisodium dihydrogen 2-phosphonatobutane-1,2,4-tricarboxylate
- Lot/batch No.: Product-No.: 403334-01. Sample No.: 807168//1988

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: Male rats: 9 weeks Female rats: 16 weeks
- Weight at study initiation: Male rats: 236 g Female rats: 217 g
- Housing:
- Diet: Conventional laboratory diet with ad libitum
- Water: Drinking water with libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/- 2°C
- Humidity (%): 50+/- 10%
- Air changes (per hr): 10 times
- Photoperiod (hrs dark / hrs light): 12 dark-/12 light

- In the end of the study (after 14 days) the rats, participated in the study were killed and subjected to pathological examinations.

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Back
- % coverage: Around 10%
- Type of wrap if used: Aluminium file
REMOVAL OF TEST SUBSTANCE
- Washing (if done): With warm water
- Time after start of exposure: 24 hours


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 4000 mg/kg
- Concentration (if solution): undiluted
- Constant volume or concentration used: no

Duration of exposure:
24 hours
Doses:
4000 mg/kg bw
No. of animals per sex per dose:
5 rats
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Few times at the day of application and twice a day in the following days until the end of the study.
Weighing was done before the application of the test substance, after one week and in the end of the 14 days study.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology.
Statistics:
NA

Results and discussion

Preliminary study:
NA
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 1 300 mg/kg bw
Remarks on result:
other: based on active ingredient of a 32.6 % aqueous solution of tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate
Sex:
male/female
Dose descriptor:
LD0
Effect level:
1 300 mg/kg bw
Remarks on result:
other: based on active ingredient of a 32.6 % aqueous solution of tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate
Mortality:
No mortality during the time of the study.
Clinical signs:
Clinical signs were not observed during the study time.
Body weight:
In male rats the growing development was not disturbed. In female rats the weight changes were minor.
Gross pathology:
The pathological examination showed that one male rat had a brighter (paler) liver with stains. Another male rat had in addition to that a brighter (paler) kidney. Two of the female rats had also a brighter liver.
Other findings:
NA

Any other information on results incl. tables

No remarks.

Applicant's summary and conclusion

Executive summary:

A 32.6 % aqueous solution (4000 mg/kg bw) of tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate was examined for acute dermal toxicity. 5 male rats and 5 female rats were observed for 14 days after dermal application of the test substance. No mortality occurred during the study time. The LD50 (rat, oral) was therefore estimated as > 1300 mg/kg based on active ingredient of a 32.6 % aqueous solution of tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate. No systemic clinical symptoms or local skin changes were observed. Minor changes were observed in body weight of female rats and no influence was observed in the growing development of the male rats. In a pathological examination of the study- rats at the end of the study, it was found that one male rat had a brighter (paler) liver with stains and another male rat had in addition a brighter kidney, two female rats, had also a brighter liver. Following the mentioned results, tetrasodium hydrogen 2-phosphonatobutane-1,2,4-tricarboxylate is not to be classified as an acute toxic substance.