Registration Dossier

Toxicological information

Acute Toxicity: dermal

Currently viewing:

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Guideline study (GLP). The registered substance is a reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen (common name: diaminomethylcyclohexane or MDACH, respectively) consisting of the two isomers 4 -methylcyclohexane-1,3-diamine (CAS 13897-55-7; molecular weight approx. 128 g/mol) and 2-methylcyclohexane-1,3-diamine (CAS 13897-56-8; molecular weight approx. 128 g/mol). The registered substance was tested in several toxicity studies, which were conducted on the one hand using 4-methylcyclohexane-1,3-diamine (CAS 13897-55-7) which is the main isomer of the registered substance (up to 90%) and on the other hand the reaction product of 2,4-dinitrotoluene and 2,6-dinitrotoluene and hydrogen was tested as such (for details see read across justification, IUCLID chapter 13).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Version / remarks:
February 24, 1987
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Version / remarks:
August 1998
Qualifier:
according to
Guideline:
other: Japan MAFF Testing Guideline of 12 Nosan No. 8147 as this in line with OECD 402.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Methyl-Diamino-Cyclohexan Dihydrochlorid (test item number: 09/0548-1)
- Physical state: solid (melt) / brown
- Analytical purity: 92%
- Lot/batch No.: 9523/22
- Stability under test conditions: the stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility.
- Storage condition of test material: room temperature
- Other: the test-item was homogeneous by visual inspection.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: rat / Wistar / Crl:WI (Han) SPF from Charles River Wiga GmbH, Sandhofer Weg 7, 97633 Sulzfeld, Germany
- Age at study initiation: young adult animals (male animals approx. 8 weeks, female animals approx. 12 weeks)
- Weight at study initiation: animals of comparable weight (± 20% of the mean weight); 200.8-205.4 g in females; 226.6-241.8 g in males
- Housing: single housing in Makrolon cage, type III
- Diet (e.g. ad libitum): VRF1(P); SDS Special Diets Services, 67122 Altrip, Germany); ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26°C
- Humidity (%): 20-80%
- Photoperiod (hrs dark / hrs light): 12 h / 12 h (6.00 a.m. – 6.00 p.m. / 6.00 p.m. – 6.00 a.m.)

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Remarks:
doubly distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: ca. 40 cm² of the clipped epidermis (dorsal and dorsolateral parts of the trunk)
- % coverage: corresponds to at least 10% of the body surface
- Type of wrap if used: covering of the application site with a semi occlusive dressing (the bandage consists of four layers absorbent gauze, Ph. Eur. Lohmann GmbH & Co. KG and Fixomull stretch (adhesive fleece), Beiersdorf AG)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): rinsing of the application site with warm water
- Time after start of exposure: 24 hours after test substance application

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10 ml/kg bw
- Concentration (if solution): 17.10 and 34.20 g/100 ml, respectively for the low and high dose groups
- Constant volume or concentration used: yes
Duration of exposure:
24 hours
Doses:
1710 and 3420 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: recording of clinical signs several times on the day of administration, and at least once daily thereafter each workday for the individual animals. Determination of individual body weights shortly before administration (day 0), weekly thereafter and on the last day of observation. Check for any dead or moribund animal at least once each workday.
- Necropsy of survivors performed: yes; necropsy with gross-pathology examination on the last day of the observation period after sacrifice with CO2 in a chamber with increasing concentrations over time
- Other examinations performed: scoring of skin findings according to Draize by individual readings 30 – 60 minutes after removal of the semi-occlusive dressing (day 1), weekly thereafter, and on the last day of observation.
Statistics:
Calculations were performed using Microsoft Excel 2003 and checked with a calculator.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 420 mg/kg bw
Based on:
test mat.
Remarks on result:
other: no mortality occurred and no clinico-pathological effects were observed up to this dose level
Mortality:
No mortality occurred.
Clinical signs:
No systemic clinical signs were observed during clinical examination.
Body weight:
The mean body weight of the animals increased within the normal range throughout the study period in both dosage groups.
Mean body weight of the female animals were constant during the first post-exposure observation week but increased during the second week within the normal range in
both dosage groups.
Gross pathology:
No macroscopic pathologic abnormalities were noted in the animals (10 males and 10 females) examined on the last day of observation.
Other findings:
- Local effects: no local effects were observed.

Any other information on results incl. tables

Table 1: Body weight changes

Days after treatment

Mean body weight changes ± standard deviations

1710 mg/kg bw

3420 mg/kg bw

Males

Females

Males

Females

0

241.8 ± 8.73

200.8 ± 6.26

226.6 ± 5.81

205.4 ± 4.34

7

256.6 ± 10.31

202.4 ± 7.02

247.4 ± 10.95

209.8 ± 1.79

15

277.6 ± 13.20

209.4 ± 7.83

273.6 ± 14.71

218.8 ± 3.11

 

Applicant's summary and conclusion