1-Dodecanamine, reaction products with 1,1'-methylenebis[4-isocyanatobenzene] and 1-octanamine

Endpoint summary

Description of key information

Dermal and ocular irritation studies have been conducted on four substances in the MDI category. In vivo studies on dermal and ocular irritation have been conducted on the substances:

A mixture of: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea; 3-cyclohexyl-1-(4-(4-(3-octadecylureido)benzyl) phenyl)urea; 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea (EC 406-530-2);

3,3'-dicyclohexyl- 1,1'-methylenebis(4,1-phenylene)diurea (EC 406-370-3);

N,N''-(methylenedi-4,1-phenylene)bis[N'-octyl]urea (EC 445-760-8), and

3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea (EC 406-690-3).

In addition, an in vivo ocular irritation study is available for Polyurea, produced by reacting diphenylmethane diisocyanate with octylamine and dodecyl amine (EC 812-490-0).

No classifiable irritant responses were observed in any of the studies when applied to skin.

Substances within the category do not have chemical structures that would trigger suspicion for irritant properties. A mixture of: 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene) diurea; 3-cyclohexyl-1-(4-(4-(3-octadecylureido)benzyl)phenyl)urea; 3,3'-dioctadecyl-1,1'-methylenebis(4,1- phenylene)diurea (EC 406-530-2), 3,3'-dicyclohexyl-1,1'-methylenebis(4,1-phenylene)diurea (EC 406-370-3), 3,3'-dioctadecyl-1,1'-methylenebis(4,1-phenylene)diurea (EC 406-690-3) and Polyurea, produced by reacting diphenylmethane diisocyanate with octylamine and dodecyl amine (EC 812-490-0) demonstrated no classifiable response according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.

The substance N,N''-(methylenedi-4,1-phenylene)bis[N'-octyl]urea (EC 445-760-8), which contains two C8 structures, was reported positive for eye irritation based on ocular reactions: irritation of the conjunctivae, seen as redness and chemosis, and a slight corneal opacity in all animals on day 2, which persisted up to day 2 (one animal) or 4 (one animal). In one animal, the effects on the conjunctivae score (redness) and chemosis score were not fully reversed within the observation period of 21 days. In the other animals, the observed effects were fully reversed within 21 days. However, in this study 100 mg of the substance (a white powder with a very poor water solubility of 4.38 µg/L) was put directly onto the eye (without vehicle) and no washing was applied. It was recorded that the material was still present in the eyes >24 h after application. It is therefore most likely that the observed ocular effects have been caused by mechanical irritation rather than inherent irritative properties of the material and this study is not considered to be reliable. The overall weight of evidence leads to the conclusion that substances in the MDI category are not eye irritants according to CLP. Further eye irritation studies are ongoing with category members in order to confirm this.

No data were identified relating to irritation of the respiratory tract. Given the results from the skin and eye irritation studies, it is unlikely that MDI category members would cause significant respiratory irritation. The members of the MDI category are grease thickeners and although they were tested in the isolated form, they are only manufactured and marketed within the grease base where near stoichiometric quantities of starting materials are used to avoid the presence of excess isocyanate. Additionally, following the substance identification analysis conducted, it is noted in all the study reports that no unreacted MDI starting material is present in the substances to be registered. Based on this information, it is considered that a respiratory classification is not required for any of the substances being registered in the MDI category. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.

Qualifier:

according to guideline

Guideline:

other: Annex V

GLP compliance:

yes

Species:

rabbit

Strain:

other: Japanese White

Type of coverage:

occlusive

Preparation of test site:

not specified

Vehicle:

other: Liquid paraffin

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

VEHICLE
- Other: Liquid paraffin

Duration of treatment / exposure:

4 hours

Observation period:

Not reported

Number of animals:

6

Details on study design:

Conducted according to guideline and GLP

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

erythema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

erythema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

erythema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

edema score

Basis:

animal #4

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

edema score

Basis:

animal #5

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritation parameter:

edema score

Basis:

animal #6

Time point:

24/48/72 h

Score:

0

Max. score:

0

Reversibility:

not specified

Remarks on result:

other: Timepoint not specified, standard timepoint assumed

Irritant / corrosive response data:

None reported

Other effects:

None

Interpretation of results:

GHS criteria not met

Conclusions:

Edema and erythema scores were 0 for all animals. Therefore, the test item is not classified for skin irritation.

Executive summary:

The skin irritancy potential of the test item was assessed using 500 mg of the test item. The study was conducted according to a standard guideline using Japanese white rabbits. The mean and max edema and erythema scores were 0 for all animals. No other effects were observed. Therefore, the test item is not classified for skin irritation.

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

Reference 2

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.

Qualifier:

according to guideline

Guideline:

other: Annex V

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

water

Remarks:

Milli-Q water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): 500 mg

Duration of treatment / exposure:

4 hours

Observation period:

Not reported

Number of animals:

3

Details on study design:

Conducted according to guideline and GLP

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

72 h

Score:

0

Irritant / corrosive response data:

Any changes observed were fully reversible within 1 day

Other effects:

Slight erythema was noted in one animal after removal of dressing.

Interpretation of results:

GHS criteria not met

Conclusions:

Mean edema and erythema scores after 24, 48 and 72 hours were 0 for all animals. Therefore, the test item is not classified for skin irritation.

Executive summary:

The skin irritancy potential of the test item was assessed with New Zealand White rabbits according to a standard guideline. 500 mg of the test item was applied to 3 rabbits and the exposure period was 4 hours. The edema and erythema scores after 24, 48 and 72 hours were 0 for all animals. Slight erythema was noted in one animal after removal of dressing. Any changes observed were fully reversible within 1 day. Therefore, the test item is not classified for skin irritation.

 

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

Reference 3

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.

Qualifier:

according to guideline

Guideline:

other: Annex V

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

other:

Remarks:

Substance moistened with water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

Duration of treatment / exposure:

4 hours

Observation period:

Not reported

Number of animals:

3

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

Mean Score 1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

Mean Score 2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

Mean Score 3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

Mean Score 1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

Mean Score 2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

Mean Score 3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Irritant / corrosive response data:

None reported

Other effects:

None

Interpretation of results:

GHS criteria not met

Conclusions:

Mean and maximum edema and erythema scores were 0 for all animals at all timepoints assessed. Therefore, the test item is not classified for skin irritation.

Executive summary:

The skin irritancy potential of the test item was assessed in a study conducted according to EU Annex V guidelines. 500 mg of test item was applied to 3 New Zealand White rabbits. The mean and maximum edema and erythema scores were 0 for all animals. No other effects were observed. Therefore, the test item is not classified for skin irritation.

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

Reference 4

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Remarks:

This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Type of coverage:

semiocclusive

Preparation of test site:

not specified

Vehicle:

unchanged (no vehicle)

Remarks:

Substance wetted with reverse osmosis purified water

Controls:

not specified

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

Duration of treatment / exposure:

4 hours

Observation period:

Not reported

Number of animals:

3

Details on study design:

Conducted according to guideline and GLP

Irritation parameter:

erythema score

Basis:

animal #1

Remarks:

Mean Score 1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #2

Remarks:

Mean Score 2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

animal #3

Remarks:

Mean Score 3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: Not reported

Score:

0

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

Mean Score 1

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #2

Remarks:

Mean Score 2

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

animal #3

Remarks:

Mean Score 3

Time point:

24/48/72 h

Score:

0

Irritation parameter:

edema score

Basis:

mean

Time point:

other: Not reported

Score:

0

Irritant / corrosive response data:

None reported

Other effects:

None

Interpretation of results:

GHS criteria not met

Conclusions:

Mean and maximum edema and erythema scores were 0 for all animals at all timepoints assessed. Therefore, the test item is not classified for skin irritation.

Executive summary:

The skin irritancy potential of the test item was assessed with a 500 mg application to New Zealand White rabbits in a study conducted according to according to a OECD 404 and EU B4 guidelines. The mean and maximum edema and erythema scores were 0 for all animals. No other effects were observed. Therefore, the test item is not classified for skin irritation.

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The category members are not classified as irritant to skin as all the in vivo rabbit studies on MDI category members were negative.

Category members are also not classified for eye irritation. Although the study conducted with N,N''-(methylenedi-4,1-phenylene) bis[N'-octyl]urea (EC 445-760-8), which contains C8 structures, indicated irreversible effects at the end of the observation period, this study is not considered to be reliable as the test item was administered as a powder, without vehicle, and no rinsing was conducted. All other studies for category members concluded that the substances are not eye irritants, and further testing is ongoing with category members to confirm this.