Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Meets generally accepted scientifical standards, well documented and acceptable for assessment.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1976
Report Date:
1976

Materials and methods

Principles of method if other than guideline:
Noakes, D.N. and Sanderson, D.M.: A Method for Determining the Dermal Toxicity of Pesticides. Brit. J. Industr. Med. 26,59 (1969).
GLP compliance:
no
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 4,4'-Diaminodiphenylmethane
- Analytical purity: > 98%

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: SPF-breed, Wiga, Sulzfeld, Germany
- Weight at study initiation: 155 g
- Diet: Altromin-R, Lage, Germany, ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
other: water or DMSO
Details on dermal exposure:
TEST SITE
shaved skin of back- and side flank, under semiocclusive cover, permeable to air.
- Area of exposure: 50 cm2

REMOVAL OF TEST SUBSTANCE
- Washing: no data

TEST MATERIAL
- Concentration: 50%



Duration of exposure:
24 h
Doses:
Aqueous solution: 1000 mg/kg and 2500 mg/kg bw
DMSO solution: 500, 1000, 1250, 2000, 2500 mg/kg bw
No. of animals per sex per dose:
10
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
Statistics:
Litchfield and Wilcoxon

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 080 mg/kg bw
95% CL:
1 631 - 2 652
Remarks on result:
other: 50% DMSO solution
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Remarks on result:
other: 50% aqueous solution, no mortalities
Mortality:
50% DMSO solution: at 1000 mg/kg bw and higher, animals started to die during the first week (see table 1).
50% aqueous solution: no mortalities
Clinical signs:
50% DMSO solution:
Animals at all doses displayed marked apathy, hyperchromodacryorrhea, and intensely stained yellow urine. At the dose levels of 500-2000 mg/kg bw, poisoning symptoms were no longer observed 6-9 days after the beginning of the test.
At the dose level of 2500 mg/kg bw in 4 of 20 animals a general jaundice was observed. This observation occured from day 4 after application and was reversible within 14 days.
50% aqueous solution: no substance related signs of toxicity
Body weight:
no data
Gross pathology:
50% DMSO solution: animals which died, and some of those sacrificed after 14 days, exhibited a bright, clay-coloured to yellowish colour change of the liver parenchyma. In the case of the 2500 mg/kg bw dose group, some of the 10 animals which died displayed an extreme, general jaundice, and some displayed a slimy to bloody enteritis, as well as bleeding stomach ulcers.
50% aqueous solution: no effects

Any other information on results incl. tables

Table 1: Mortalities after application of 50% MDA in DMSO

500 mg/kg bw 1000 mg/kg bw 1250 mg/kg bw 2000 mg/kg bw 2500 mg/kg bw
male female male female male female male female male female
1 h 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10
1 d 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10
2 d 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10 0/10
7 d 0/10 0/10 0/10 5/10 0/10 0/10 2/10 9/10 3/10 7/10
14 d 0/10 0/10 0/10 5/10 0/10 0/10 2/10 9/10 3/10 7/10

Applicant's summary and conclusion