Trisodium nitrilotriacetate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

short-term repeated dose toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: small group size; limited data on method

Data source

Reference

Reference Type:

publication

Title:

Toxicity Evaluation of Trisodium Nitrilotriacetate

Author:

Nixon, G.A.

Year:

1971

Bibliographic source:

Toxicol. Appl. Pharmacol. 22, p. 297

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Na3NTA was was applied to the clipped and abraded backs of each of 6 New Zealand rabbits for a period of 28 days (20 treatments) and 91 days (65 treatments; 5 days/week; intact skin). At sacrificed all animals were examined hematological and histological.

GLP compliance:

no

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Trisodium nitrilotriacetate

EC Number:

225-768-6

EC Name:

Trisodium nitrilotriacetate

Cas Number:

5064-31-3

Molecular formula:

C6H9NO6.3Na

IUPAC Name:

trisodium 2-[bis(carboxylatomethyl)amino]acetate

Details on test material:

- Name of test material (as cited in study report): Trisodium Nitrilotriacetate
- Physical state: liquid (2,5% aqueuous solution) or solution of granular detertgent containing 10.0 and 11.0% Na3NTA

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

not specified

Administration / exposure

Type of coverage:

not specified

Vehicle:

water

Details on exposure:

2 ml/kg/day of a 2.5 % aqueous solution of Na3NTA (50 mg/kg/day) was applied to the clipped and abraded backs of each of 6 New Zealand rabbits for a period of 28 days (20 treatments) and 91 days (65 treatments; 5 days/week; intact skin). At sacrificed all animals were examined hematological and histological.
2 ml/kg of a 10.0 % solution of granular detergent containing 10.0 % Na.NTA was also applied daily for 5 days each week to the intact skin of 6 albino rabbits for 91 days (65 treatments) while a similar formulation containing 11% Na3NTA was applied at the same dose level to a group of 6 animals (abraded skin) for 28 days (20 treatments).

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 or 91 days

Frequency of treatment:

5 days/week

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 50 mg/kg
Basis:
other: 2.5% x 2 ml

No. of animals per sex per dose:

6 animals per dose

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

All animals in these studies were weighed weekly, and the treated areas were observed daily for primary irritation.

Sacrifice and pathology:

At sacrificed hematological and histological examination of blood and tissues was conducted in all animals

Results and discussion

Effect levels

Dose descriptor:

NOAEL

Effect level:

50 mg/kg bw/day

Sex:

not specified

Basis for effect level:

other: Microscopic tissue examination showed only mild skin irritation

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

Application of 50 mg/kg Na3NTA (2.0 ml/kg of 2.5% solutions) to the shaved backs of rabbits for 28 (abraded skin) or 91 days (intact skin), caused no adverse gross effects. Growth, organ to body weight ratios, and hematologic values were within normal limits and were not significantly different from animals treated with 2 ml/kg/day of water. Histological examination of tissues from sacrificed animals revealed no abnormalities. Nothing unusual was seen during necropsy in animals treated for 28 and 91 days with detergents containing 11% and 12% Na3NTA. respectively. Microscopic tissue examination showed only mild skin irritation. Average body weights, organ/body weight ratios. and hematologic values were normal.

Applicant's summary and conclusion

Conclusions:

In a repeated dose dermal toxicity study, Na3NTA was applied to the shaved skin of 6 New Zealand White rabbits at 50 mg/kg bw/day 5 days/week during a 28-day period and to intact skin for a 91-day period. No effects besides a mild skin irritation were reported.

Executive summary:

In a repeat-dose dermal toxicity study, Na3NTA (no data on purity) was applied to the shaved skin of 6 New Zealand white rabbits at 50 mg/kg bw/day 5 days/week during a 28-day period and to intact skin for a 91-day period.

There were no compound related effects on mortality, clinical signs, body weight changes, changes in food consumption, hematology, clinical chemistry, organ weights, or gross and histologic pathology. Microscopic tissue examination showed only mild skin irritation.

The NOAEL is 50 mg/kg based on the maximum applied concentration.

This dermal toxicity study in the rabbits is unacceptable (Significant methodological deficiencies: applied concentration too low for a Limit test (50 mg/kg instead of 2000 mg/kg); small group size (6 instead of 20; limited data on test compound and method) and does not satisfy the guideline requirement for a repeated dose dermal toxicity study (OECD 411 in rabbit).