Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8 February 1989 - 22 February 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was peformed according to OECD guidelines and GLP.

Data source

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

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: M-3175; 1,3-propylenediamine-N,N,N',N'-tetra acetic acid, ammonium iron (+3) salt (mentioned in 28-day study report)
Appearance: yellow powder
Batch No.: VG-01
Purity: 99% (mentioned in 28-day study report)

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (U.K.) Limited, Margate, Kent, England
- Age at study initiation: ± 8 weeks
- Weight at study initiation: 215 - 258 g for males and 218 - 243 g for females
- Housing: The animals were housed in Type RC1 cages consisting of a high density polypropylene body, measuring 56 x 38 x 18 cm, with
stainless steel grid floors and tops (North Kent Plastics Limited, Dartford, Kent, England). The grid floors ensured rapid removal of waste material to undertrayswhich were cleaned as necessary. Five animals of the same sex were housed in each cage. The cages were suspended in mobile stainless steel racks. On completion of dosing, the animals were accommodated individually in Type RB3 cages measuring 45 x 28 x 20 cm (North Kent Plastics Limited, Dartford, Kent, England).
- Diet (e.g. ad libitum): A commercially available complete pelleted rodent diet (Laboratory Animal Diet No. 1 from Labsure, Manea, Cambridgeshire) was fed without restriction.
- Water (e.g. ad libitum): Animals had free access to tap water supplied in a single bottle per cage and re-filled as required.
- Acclimation period: at least 5 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-25
- Humidity (%): 40-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 8 February 1989 - 22 February 1989

Administration / exposure

Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: back
- % coverage: no data
- Type of wrap if used: the test substance covered by an unmedicated gauze, and was occluded with aluminium foil. The foil was kept in place and protected by a bandage of waterproof plaster ("Sleek", Smith and Nephew Limited) wrapped tWice around the trunk of the body with sufficient tension to ensure the dose remained securely in place.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The dermal site was gently wiped with wet disposable towels to remove residual test material.
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw, rats weigh ± 250 g, ± 0.5 g per rat. The dose was determined-for each animal according to its bodyweight on the morning of dosing.
- For solids, paste formed: no, but moistened with 0.2 ml water.
Duration of exposure:
24 hours
Doses:
2000 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: Three separate inspections were made during the first hour after administration and two further inspections during the remainder of Day 1. From Day 2 onwards, the animals were inspected twice daily (morning and afternoon). Each dermal application site was examined at the morning observation. The type, time of onset and duration of reactions to treatment were recorded. The bodyweight of each animal was recorded on the day before dosing and on Days 1, 8 and 15. The test was terminated on Day 15.
- Necropsy of survivors performed: yes
Statistics:
None

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no death.
Clinical signs:
There were no systemic or local signs of reaction to treatment.
Body weight:
All animals achieved anticipated bodyweight gains.
Gross pathology:
Necropsy revealed enlarged cervical lymph nodes in all females, an abnormal shaped sternum in two females and fluid distension of the uterus in one other animal. None of these changes were considered to reflect an effect of treatment with M-3175.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
LD50> 2000 mg/kg bw
Executive summary:

The acute percutaneous toxicity of M-3175 was investigated in one group of five male and five female CD rats. The test material was applied to the closely-clipped dorsum of each animal on day 1 a dosage of 2000 mg/kg, and was covered by an occlusive dressing for 24 hours. Systemic or local signs of reaction to treatment were recorded during a subsequent 14-day period of observation. All animals were killed on Day 15 and subjected to necropsy. There was no death. There were no systemic or local signs of reaction to treatment. All animals achieved anticipated bodyweight gains. There were no macropathoiogical observations considered to reflect an effect of M-3175. Under the conditions of this study, the acute percutaneous median lethal dosage (LD50) of the test material was greater than 2000 mg/kg.