Decyldimethylamine

Endpoint summary

Description of key information

Reliable studies on skin irritation/corrosion are available for the DMA category members C10-DMA, C12-DMA, C12-14-DMA, C14-DMA, C16-DMA, C12-18-DMA, C16-18-DMA, and C18-DMA. All studies were performed according to the OECD Guideline 404. The DMAs of this category caused skin irritant up to corrosive effects. Therefore, a classification as Skin Corr. 1B according to Regulation (EC) No 1272/2008 is warranted. No tendency related to increasing carbon chain length is observed.

Reliable in vivo studies on eye irritation/damage are available for the DMA category members C12-14-DMA, C14-DMA and C16-DMA. These studies were conducted according to the OECD Guideline 405. The DMAs of this category caused irreversible eye damaging effects. The substances of the DMA category have to be classified to cause irreversible damage to the eyes (Cat. 1) following the criteria of Regulation (EC) No. 1272/2008. No tendency related to increasing carbon chain length is observed. As endpoint conclusion the most conservative value for the category members is selected.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

From 24 SEP 1987 to 10 NOV 1987

Justification for type of information:

For details on endpoint-specific justification, please see read-across justification document (category approach) in the linked category of dimethylalkylamines.

Irritation parameter:

erythema score

Basis:

mean

Remarks:

test item exposure: 4 h

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

other: reversibiliy cannot be determined due to other skin effects

Remarks on result:

other: effects after 14 days: glossy skin, desquamation

Irritation parameter:

edema score

Basis:

animal #1

Remarks:

test item exposure: 4h

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

fully reversible within: 14 days

Irritation parameter:

edema score

Basis:

mean

Remarks:

animal #2 and #3, test item exposure: 4 h

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

fully reversible within: 14 days

Results presented above were obtained with the source substance C12-18 DMA.

 

Additional results for C12-18 DMA:

 

three minutes exposure

Skin reaction	Reading (hours)	Individual scores - rabbit number 1 -3
Erythema / eschar formation	1	1	1	1
	24	2	2	2
	48	2	2	2
	72	2 D	3 D	2 D
	7 Days	HyCrTL	HyCrTL	HyCr
	14 Days	0	0	0
Oedema formation	1	1	1	1
	24	2	2	2
	48	2	2	1
	72	2	2	1
	7 Days	0	0	0
	14 Days	0	0	0

 

One hour exposure

Skin reaction	Reading (hours)	Individual scores - rabbit number 1 -3
Erythema / eschar formation	1	2	1	1
	24	2 Br	2	2 Br
	48	2 Br	2	2 Br
	72	2 Br	2	2 Br
	7 Days	HyCrTL	HyTL	HyCrTL
	14 Days	Fa	FaD	Fa
Oedema formation	1	2	1	1
	24	2	2	2
	48	2	2	2
	72	2	2	2
	7 Days	0	0	0
	14 Days	0	0	0

 

four hour exposure

Skin reaction	Reading (hours)	Individual scores - rabbit number 4 -6
Erythema / eschar formation	1	2 H	2 H	2 H
	24	4 MBE	4 EMB	4 EMB
	48	4 WBHE	4 EMB	4 EMB
	72	4 WBE	4 EWB	4 EMB
	7 Days	EHY	Eg	BsEgHy
	14 Days	GsD	GsD	GsD
Total 24, 48 and 72 hours		12	12	12
Mean Values		4	4	4
Oedema formation	1	4 0e	4 0e	3
	24	4 0e	4 0e	4 0e
	48	4 0e	3 0e	3 0e
	72	3	3	3
	7 Days	1	1	0
	14 Days	0	0	0
Total 24, 48 and 72 hours		11	10	10
Mean Values		3,7	3,3	3,3

 

B = blanching of skin surrounding treatment site

Fa = abnormal fur growth - fur growing in various directions

Br= brown areas over treatment site

0e= oedema extending ventrally beyond site

D= desquamation

Hy= dry, straw-coloured skin (possible hyperkeratinisation)

Cr= superficial cracking of skin

T= thickening of skin

L= loss of skin suppleness

M= moderate to severe erythema extending beyond treatment site

W= well-definded erythe,a extending beyond treatment site

E= eschar of dry, straw-coloured sin (possible hyperkeratinsation) surrounding eschar

Eg= eschar lifting to reveal glossy skin

Bs= focal areas of dried, blood stained tissue

Gs= glossy skin

D= desquamation

Executive summary:

The study used as source investigated skin irritation/corrosion of C12-18 DMA. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in the linked category of dimethylalkylamines.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Justification for type of information:

For details on endpoint-specific justification, please see read-across justification document (category approach) in the linked category of dimethylalkylamines.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: no effects observed

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

2

Reversibility:

not fully reversible within: 22 days

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

not fully reversible within: 22 days

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.23

Max. score:

4

Reversibility:

not fully reversible within: 22 days

 

Results presented above were obtained with the source substance C16-DMA.

 

Additional results for C16-DMA:

 

Mean valuea for occulat lesions 24, 48 and 72 h after instillation

Animal number and sex	Corneal opacity	Iridial lesions	Redness of Conjunctiva	Chemosis
27TK490F	0	1	1	2
27TK533F	0	1	1	0,7
27TK534F	0	0	1	1

 

Grades for occular irritation responses

Animal No. and Sex: 27TK490F#		Pain evaluation response: 0
Region of the eye	Response		Grade of response at time alter instillation Hours              Days
		1	24	48	72	8	15	22
Comea	Opacity	0	0	0	0	0	0	0
	Area	0	0	0	0	0	0	0
	Ulceration
	Stippling
Iris	Value	1	1	1	1	0	0	1
Conjunctiva	Redness	2	1	1	1	*	*	1
	Chemosis	0	2	2	2A	OA	OA	0
	Discharge	2	1	1	2	*	*	1
	Necrosis	-
	Ulceration	-	-
							BC	BC

 

Grades for occular irritation responses

Animal No. and Sex: 27TK534F		Pain evaluation response: 0
Region of the eye	Response		Grade of response at time alter instillation Hours           Days
		1	24	48	72	8	15	22
Cornea	Opacity	0	0	0	0	0	0	0
	Area	0	0	0	0	0	0	0
	Ulceration
	Stippling							-
Iris	Value	1	0	0	0	0	0	0
Conjunctiva	Redness	1	1	1	1	1	1	1
	Chemosis	I	2A	IA	OA	OA	OA	0
	Discharge	1	1	0	0	1	0	0
	Necrosis
	Ulceration
							BC	BC

 

#Sentinel animal

* Impossible to open eye sufficiently to assess

A Blepharitis

B Peri-orbital exfoliation

C Peri-orbital hair loss

Executive summary:

The study used as source investigated eye irritation/corrosion of C16-DMA. The study results of the source compound were considered applicable to the target compound. Justification and applicability of the read-across approach (category approach) is outlined in the read-across report in the linked category of dimethylalkylamines.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Eighteen reliable in vivo skin irritation studies (reliability 1) are available for C10-DMA, C12-DMA, C12-14-DMA, C14-DMA, C16-DMA, C12-18-DMA, C16-18-DMA and C18-DMA. All studies were performed according to the OECD Guideline 404.

Additionally, for C12-14-DMA and for C16-18-DMA reliable in vitro studies according to OECD 431 are available. For C16-DMA and C12-18-DMA, three studies of lower reliability (reliability 3) are reported as well.

In six reliable studies the results are indicating that the test substances are irritating to skin (C10-DMA, C12-DMA, C14-DMA, C16-DMA, C18-DMA). Except for C14-DMA and C18-DMA, for which only irritant effects were observed, additional studies for the other substances also point to corrosive effects. Altogether, there are twelve reliable studies indicating a corrosive effect of the test substances on the skin.

Only four of these twelve studies were performed with exposure times ≤ 4 h and observation periods of at least 14 days allowing a more detailed classification in corrosive subcategories 1A, 1B or 1C according to Regulation (EC) No. 1272/2008. These studies point to subcategory 1A for C12-DMA, subcategory 1B for C12-18-DMA and subcategory 1C for C12-18-DMA (2 studies) as well. The studies for the subcategories show slight differences, for which the reasons are not obvious, as all studies were reliable and according to OECD guidelines. The differences are possibly due to biological variance. The most contradicting results were obtained for C12-DMA: one study indicating subcategory 1A and another one revealed only irritating effects. The study with the corrosive effects after 3 minutes exposure was possibly an outlier. C12-18-DMA was found to be corrosive in one study after 1 h of exposure (subcategory 1B) and in two other studies after 4 hours of exposure (subcategory 1C). Besides other effects, scar formation was observed in animals treated for one hour indicating that the substance induces skin corrosion already after short-term exposure. Altogether, across the substances belonging to the DMA category, the study results are comparable and an effect correlation to the alkyl chain length could not be derived. After four hours skin exposure to DMAs, the animals exhibited initially erythema and edema (slight to severe) followed by skin alterations such as eschar formation, thickening of the skin, incrustation up to scar formation etc., indicating severe skin damage.

The three non-reliable studies (reliability 3) could not be used for classification due to the short observation time of 48 h. However, within these 48 h of observation, serious effects were observed indicating corrosive properties of the test substances, supporting the results from the reliable studies.

The data reported in the in vitro tests are contradicting the results observed in vivo. In tests according to OECD guideline 431, a corrosive potential of test substances can be assessed in reconstructed human epidermis. For C12-14-DMA and C16-18-DMA, non-corrosiveness was observed in this test. However, due to the strong evidence of corrosiveness in vivo, the results of these test are not considered relevant for classification.

Based on the available in vivo data, it is concluded that the substances of the DMA-category should be classified as skin corrosive (subcategory 1B) according to Regulation (EC) No. 1272/2008 (CLP). A classification as skin corrosive (subcategory 1A) does not seem to be justified as this single finding for one substance was not confirmed by studies with other members of the category and contradicted by a second study for the same substance, which indicated only irritating effects.

Four reliable in vivo eye irritation studies (reliability 1) are available for C12-14-DMA, C14-DMA and C16-DMA. These studies were conducted according to the OECD Guideline 405.

In all four studies the treatment related effects are comparable: the primary effects observed in the first week were iritis and conjunctivitis followed by blepharitis in the second and third week. Towards end of the observation period the treated animals displayed peri-orbital exfoliation, peri-orbital hair loss and peri-orbital sloughing. The treatment related effects were not fully reversible within 14 days or even longer observation times, i.e. the substances caused irreversible damage to the eyes.

For C12-14-DMA and C16-18-DMA four reliable in vitro eye irritation/corrosion tests were performed. For each substance one test was performed according to OECD guideline 437 and another one with EpiOcular™ which is a three-dimensional in vitro model of the human corneal epithelium. The results of these tests are contradicting for each substance: One test showed irritating results, the other non-irritating (For C12-14-DMA the OECD test result was “irritant”, the EpiOcular™ test showed non-irritant effects, for C16-18-DMA vice versa).

However due to the strong evidence of corrosiveness of C12-14-DMA and C16-18-DMA in in vivo skin studies and the irreversible damage to the eyes observed for the other members of the DMA category, the less severe effects observed for C12-14-DMA and C16-18-DMA in these in vitro tests are not considered relevant for classification. Taking into account the severe effects on the eye observed in the available in vivo studies as well as the skin corrosive properties of these substances, DMA category members have to be classified as causing irreversible damage to the eyes (category 1).

No studies are available to evaluate respiratory irritation.

 

Justification for classification or non-classification

According to the results of available studies for the members of the DMA category, these substances are already corrosive to skin after exposure times of > 3 minutes and ≤ 1 h. Therefore, they fulfil the criteria to be classified as skin corrosive substance (subcategory 1B) following the criteria of Regulation (EC) No. 1272/2008 (CLP) and should be classified as corrosive according to Council Directive 67/548/EEC (R34).

According to the results of available studies for the members of the DMA category, the substances of the DMA category have to be classified to cause irreversible damage to the eyes (Cat. 1) following the criteria of Regulation (EC) No. 1272/2008.