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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
26 April to 10 May 1989
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study, equivalent to guidelines available at the time; on related material

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): trisodium EDDS (under code)
- Molecular formula (if other than submission substance): C10-H13-N2-O8. 3Na
- Molecular weight (if other than submission substance): 358
- Smiles notation (if other than submission substance): [Na+].[Na+].[Na+].OC(=O)[C@H](CC([O-])=O)NCCNC(CC([O-])=O)C([O-])=O
- Substance type: technical product
- Physical state: white, granular powder
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: March 1990
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature

Test animals

Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire, UK
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 2.3-2.7 kg (although report states 2.3-2.7 g)
- Fasting period before study: no
- Housing: individually in metal cages with perforated floors
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-21.0
- Humidity (%): mean 52
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
used to moisten the test substance and aid adhesion to the skin
Details on dermal exposure:
TEST SITE
- Area of exposure: dorso-lumbar region
- % coverage: 10
- Type of wrap if used: gauze held in place with a "non-occlusive" dressing encirclating the trunk

REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (30-40oC) and blotted dry
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2.64 mL/kg bw
- For solids, paste formed: no (moistened with water after application)

VEHICLE
- Amount(s) applied (volume or weight with unit): 2.64 mL/kg bw
Duration of exposure:
24 h
Doses:
2640 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed at "frequent intervals" on day of dosing, then at least twice daily until study termination. Weighed before dosing, then weekly
- Necropsy of survivors performed: yes
- Other examinations performed: macroscopic examination of abdominal and thoracic cavities
other: erythema, eschar formation, oedema of the test site scored daily
Statistics:
not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 640 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CLs not applicable
Mortality:
No deaths occurred during the study
Clinical signs:
Diarrhoea was observed in 3 males and 3 females lasting about 2 days for each animal, but this was not considered to be treatment-related
Body weight:
Loss in body weight was recorded for 2 males and 1 female on day 8. Low body weight gains were observed for 1 female on day 8 and 1 male on day 15
Gross pathology:
No abnormalities were observed following macroscopic examination of the thoracic and abdominal organs and tissues
Other findings:
No irritation reactions were detected

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a GLP study conducted according to OECD Guideline 402 (available at the time), an acute dermal 24-h LD50 value of >2640 mg/kg bw was determined for trisodium EDDS in male and female rabbits following semi-occlusive application.
Executive summary:

In a GLP study conducted according to OECD Guideline 402 (available at the time), the acute dermal toxicity of trisodium EDDS was assessed in male and female New Zealand White rabbits. The test powder (2.64 g/kg bw) was applied to the clipped backs of five rabbits of each sex, moistened with water to aid adhesion to the skin and covered with a semi-occlusive dressing for 24 h. The test substance was subsequently removed by washing in warm water and blotting dry. The animals were observed for 14 days for mortality, clinical signs of systemic toxicity, irritation of the application area and body weight changes, after which they were killed and the organs of the thoracic and abdominal cavities were examined macroscopically.

No clinical signs of toxicity were seen in any of the animals and no deaths occurred during the 14-d observation period. Diarrhoea, lasting about 2 days in three animals of each sex was not considered to be treatment-related. At necropsy, no gross changes in organs or tissues were detected.

An acute dermal 24-h LD50 value of >2640 mg/kg bw was determined for trisodium EDDS in male and female rabbits. According to EU CLP and DSD regulations, trisodium EDDS would not be classified as acutely toxic by the dermal route under the conditions of this test.

[Data on trisodium EDDS is considered relevant to use for understanding the potential acute toxicity, dermal of EDDS acid, and is acceptable for using as read-across information].