Trisodium dihydrogen -N,N-[bis[2-[bis(carboxylatomethyl)amino]ethyl]]glycinate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January 1987

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No data on batch number and composition; basic data given; comparable to guidelines/standards (max. reliability score can be 2)

Justification for type of information:

The source substance (DTPA 5K) and the target substance (DTPA 3Na) are the pentapotassium and trisodium salts of the same organic acid and are therefore structurally very similar. The purity/impurity profile for the source material is not characterised in the acute dermal toxicity robust summary, but since the target material is > 99.9% pure and contains no detectable impurities, the extrapolation of acute dermal toxicological properties from the source material to the target material is considered valid as a ‘worst case' scenario. The source material acute dermall toxicity study was conducted according to OECD test guideline 402 and is considered reliable with restrictions (Category 2).

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1987

Report date:

1987

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes

Remarks:

audited in-house

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

7216-95-7

Cas Number:

7216-95-7

IUPAC Name:

7216-95-7

Details on test material:

No batch number and composition indicated in the report.
Appearance: white solid
Date of receipt: 5 January 1987
Stored at ambient temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Interfauna UK, Ltd., Huntingon, UK
- Age at study initiation: 7-10 weeks
- Weight at study initiation: 200-249 g
- Fasting period before study: no
- Housing: individually in metal cages with wire mesh floor
- Diet (e.g. ad libitum): ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 50 (mean)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 13 To: 27 January 1987

Administration / exposure

Type of coverage:

occlusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: ca. 10% of total body surface
- % coverage: 10% of total body surface
- Type of wrap if used: gauze held in place with an impermeable dressing encircled around the trunk


REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (30-40 degrees C)
- Time after start of exposure: 24 h


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.20 mL/kg bw
- Concentration (if solution): 90% w/v paste in distilled water
- Constant volume or concentration used: 2.20 mL/kg bw
- For solids, paste formed: yes


VEHICLE
- Amount(s) applied (volume or weight with unit): see above (2.20 mL/kg bw)
- Concentration (if solution): 90% w/v

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations twice daily, BW weekly.
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

Not performed.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality

Clinical signs:

other: No clinical signs of systemic reactions present.

Gross pathology:

No macroscopic changes noted.

Other findings:

Dermal responses:
The sites of application showed no general inflammatory responses, but 9 animals developed multiple minute encrustations on the
treated skin. These were first apparent on day 4 and resolved completely by day 9.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The acute dermal LD50 is > 2000 mg/kg bw.

Executive summary:

The study was performed to assess the acute toxicity of the test material following a single dermal administration to the Sprague-Dawley

strain rat. The procedure permitted identification of the LD50 value. The study was performed according to OECD guideline 402 and Method B3 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

A group of ten animals (five male and five female) was given a single, dermal dose of the test material (lasting 24 hours) at a dose level of 2000 mg/kg bodyweight. The animals were observed for 14 days after the day of dosing and were then killed for gross pathological examination. There were no deaths. No clinical signs of systemic toxicity were noted. No inflammatory responses were noted, but 9/10 animals showed multiple minute encrustations on the treated skin on days 4 -9. Male animals showed expected gains in bodyweight over the study period, low body weight gains were noted in 4/5 females. No abnormalities were noted at necropsy.

The acute median lethal dose (LD50) of the test material was found to be greater than 2000 mg/kg bodyweight.

The test material was considered not to have significant acute toxicity and does not require classification as harmful, toxic or very toxic according to the EC scheme and GHS scheme.