Carbamic acid, N,N'-methylenebis(4,1-cyclohexanediyl)bis-, C,C'-dibutyl ester

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2003-11-04 to 2003-11-20

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

Acute Toxic Class Method

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Japanese test guidline (2000)

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,4'-Methylenebis(N-butoxycarbonylcyclohexanamine)

EC Number:

619-422-7

Cas Number:

99305-42-7

Molecular formula:

C23 H42 N2 O4

IUPAC Name:

4,4'-Methylenebis(N-butoxycarbonylcyclohexanamine)

Details on test material:

4,4'-Methylenebis(N-butoxycarbonylcyclohexanamine of Degussa AG, batch 4/032, purity not indicated by the sponsor, treated as 100 % pure

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- strain: Wistar strain Crl:(WI) BR (outbred, SPF-Quality); Source: Charles River Deutschland,
- Age at study initiation: young adult animals, approx. 10 weeks old
- Fasting period before study: max. 20 hours prior to dosing until 3-4 hours after administration
- Housing: group housing of 3 animals
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21,0 +/- 3,0 °C
- Humidity (%): 30 - 70 % (actual range: 39 - 67 %)
- Air changes (per hr): 15 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours light/ 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

ADMINISTRATION/EXPOSURE 
- Dose level: 2000 mg/kg (10ml/kg) body weight
- Oral gavage, using a stainless steel stomach tube
- single dosage, day 1
- Vehicle: propylene glycol was selected based on trial formulations
CLASS METHOD
- Rationale for the selection of the starting dose:Toxicity was assessed by stepwise treatment of groups of 3 animals, first group was treated at
a dose level of 2000 mg/kg body weight.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

EXAMINATIONS
Mortality/Viability: twice daily   
Body weights: day 1 (pre-administration), 8, 15
Clinical signs: at peridoc intervals on dosing day, once daily thereafter
Necropsy: descriptions of all internal macroscopic abnormalities were recorded

Statistics:

no statistical analysis was performed

Results and discussion

Preliminary study:

not available

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Remarks on result:

other: Limit test

Mortality:

No mortality occurred

Clinical signs:

other: Hunched posture was noted among all animals on day 1. In addition, all females showed quick breathing and piloerection on day 1.

Gross pathology:

No toxicologically relevant abnormalities were found at macroscopic examination of the animals. Incidental findings included fluid in the uterus
(one female) and dark red foci on the thymus (one male). These findings are occasionally seen among rats of this age and strain and were therefore
considered of no toxicological significance.

Other findings:

no other findings

Any other information on results incl. tables

no further information

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: other: EU: according to Council Directive 67/548/EEC

Conclusions:

The oral LD50 value of the test item H12MDU in Wistar rats was established to exceed 2000 mg/kg body weight. The test item possess very low toxicity after single oral gavage in rats and does not have to be classified for acute toxicity by the oral route according to Council Directive 67/548/EEC.

Executive summary:

The aim of the study was to assess the acute oral toxicity of the test substance H12MDU when administered in a single dose to rats of both sexes at one or more defined dosages (acute toxic class method). The oral LD50 value of the test item H12MDU in Wistar rats was established to exceed 2000 mg/kg body weight. As a conclusion accordinmg to the study the test item possess very low toxicity after single oral gavage in rats and does not have to be classified for acute toxicity by the oral route according to Council Directive 67/548/EEC.