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Diss Factsheets

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
136210-32-7
EC Number:
603-947-3
Cas Number:
136210-32-7
IUPAC Name:
136210-32-7
Constituent 2
Chemical structure
Reference substance name:
Bis(4-(1,2-bis(ethoxycarbonyl)ethylamino)-3-methylcyclohexyl)methane
EC Number:
412-060-9
EC Name:
Bis(4-(1,2-bis(ethoxycarbonyl)ethylamino)-3-methylcyclohexyl)methane
Cas Number:
136210-32-7
Molecular formula:
C31H54N2O8
IUPAC Name:
bis(4-(1,2-bis(ethoxycarbonyl)ethylamino)-3-methylcyclohexyl)methane

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Winkelmann, Borchen, Germany
- Strain: BOR: WISW (SPF Cpb)
- Age at study initiation: approximately 9 weeks for male rats and 16 weeks for female rats
- Weight at study initiation: mean weight 233 g (for males) and 222 g (for females)
- Housing: singly
- Diet and water: ad libitum
- Acclimation period: at least 5 days

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Approximately 24 h before application of the test substance the skin areas of the animals were carefully shorn.
- % coverage: approximately 10% of the bodies surface
- Type of wrap if used: covererd with gauze plus aluminium foil and fixed with a nonirritating bandage.

REMOVAL OF TEST SUBSTANCE
- Washing: If there was remaining test substance after removal of the bandage, the skin was washed with tempered water.
Duration of exposure:
approximately 24 h
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: day 0 several times, day 1 to 14 twice daily, except for the weekend (once daily)
- Frequency of weighing: immediately after application and on day 7 and day 14.
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No mortality was observed after the application or during the 14-days post-application period.
Clinical signs:
2 of 5 males and 3 of 5 females exhibited a slight erythema at the application site. This was fully reversible within 1 day, except for one female, where full reversibility was achieved on day 6. No systemic symptoms were observed.
Body weight:
Body weight gain was retarded in female rats, no effects on body weight gain were observed for male rats.
Gross pathology:
All animals were sacrificed at the end of the 14-days observation period. There were no gross pathological findings.

Any other information on results incl. tables

Study was performed with Aspartic acid, N,N'-[methylenebis(2-methyl-4,1-cyclohexanediyl)]bis-, 1,1',4,4'-tetraethyl ester which is a structural analogue to Aspartic acid, N,N'-(methylenedi-4,1-cyclohexanediyl)bis-, 1,1',4,4'-tetraethyl ester. Both substances are diethyl esters of aspartic acid linked to a dicyclohexylmethyldiamine moiety. The difference between these two substances is merely the presence of two methyl groups connected to the cyclohexane rings. This structural analogy was confirmed by the Member State responsible for the notification of both substances under the NONS regulation. The Member State decided that test results obtained for one substance can be transferred to the other substance and that testing of both substances is usually not required. This decision is in accordance with the grouping of substances and read-across approach in Annex XI, 1.5 of the REACH Regulation.

Applicant's summary and conclusion

Executive summary:

A dermal toxicity study with a limit limit dose of 2000 mg test item/kg bw was performed with 5 male and 5 female rats according to EU method B.3. No mortality and no gross pathological findings were observed after application of the test substance (aspartic acid, N,N'-[methylenebis(2-methyl-4,1-cyclohexanediyl)]bis-,1,1',4,4'-tetraethyl ester) during the 14-days post-observation period. Some male and female rats exhibited a transient slight erythema after application of the test substance. Body weight gain was retarded in female rats, but the body weight gains of male rats were not affected.

Therefore the dermal LD50 was determined to be > 2000 mg/kg bw.