bis(diethylamino)-N,N-diethylmethaniminium chloride

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

5 December 2003 to 19 December 2003

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Deviations:

no

GLP compliance:

yes

Remarks:

US EPA GLPs 40 CFR, Part 792; OECD GLPs

Test material

Test material information

Constituent 1

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Male and female New Zealand White rabbits, at least 10 weeks of age, weighing 2.07 to 2.14 kg. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages. They were provided food and tap water ad libitum. Room temperature was 68 ± 5°F and the relative humidity ranged between 30-70%. Room lights were on a 12-hour light/dark cycle.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

Approximately 24 hours prior to dosing, the application sites were prepared by clipping the skin of the trunk free of hair (not less than 10% of the body surface was clear for the application of the test substance). One half gram (0.5 mL) of the test substance was applied to a small area of the skin (approximately 6 cm²).

Duration of treatment / exposure:

Each application area was covered with a gauze patch and secured with non-irritating tape.
Initially, three test patches were applied sequentially to a single animal and removed after three minutes, one hour and then four hours of contact to assess for possible corrosion. Once it was determined that a four-hour exposure could humanely be allowed, a single test patch was applied to two additional animals for a four hour exposure period.

Observation period:

Dermal scores were recorded at 1, 24, 48 and 72 hours after patch removal. Daily clinical observations included all toxicologic and pharmacologic signs. Animals were weighed at Day 0 prior to dose administration and at the end of the observation period (Day 14).

Number of animals:

3

Details on study design:

Erythema and Edema formation were observed/scored based upon the following definitions: see tables below

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: 31649

Remarks:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 14 days

Results 2

Irritation parameter:

erythema score

Basis:

animal: 31650

Remarks:

mean

Time point:

24/48/72 h

Score:

2.33

Max. score:

3

Reversibility:

fully reversible within: 11 days

Results 3

Irritation parameter:

erythema score

Basis:

animal: 31651

Remarks:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 10 days

Results 4

Irritation parameter:

edema score

Basis:

animal: 31649

Remarks:

mean

Time point:

24/48/72 h

Score:

2.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 5

Irritation parameter:

edema score

Basis:

animal: 31650

Remarks:

mean

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 6 days

Results 6

Irritation parameter:

edema score

Basis:

animal: 31651

Remarks:

mean

Time point:

24/48/72 h

Score:

2

Max. score:

2

Reversibility:

fully reversible within: 7 days

Irritant / corrosive response data:

In the initial test, no signs of erythema or edema were present after 3 minutes. After one hour, well-defined erythema and edema was observed. Although a skin reaction was noted, the observation indicated that the exposure could humanely extend to four hours. One hour after the four hour exposure, similar scores of well-defined erythema and edema were recorded.

The additional two rabbits tested were observed to have well-defined erythema and edema at one hour after patch removal. All three rabbits showed signs of erythema and edema varying from slight to moderate at the 24 hour observation period. All rabbits continued to show well-defined to moderate erythema with signs of edema varying from slight to moderate at the 48 and 72 hour observation points.

All rabbits were scored daily up to day 14 to observe the nature and reversibility of the responses. By day four, eschar formation was observed in two rabbits and was observed on the following day in the third rabbit. During the 14 day period, a sloughing of the eschar at the dosing site occurred and the surrounding skin was noted to be dry and flaky. Signs of the erythema decreased with no signs of edema after one week. By day 11, eschar formation had resolved in two rabbits but by day 14 the presence of scar rissue and alopecia was still noted at the dosing site in one rabbit.

None of the control sites of any animal at any of the observation periods showed signs of erythema or edema.

Other effects:

All animals gained weight over the course of the study. No overt signs of toxicity were evident in any of the animals during the course of the study.

Any other information on results incl. tables

Skin Irritation Scores for the Test Sites

Observation Period*	Ob	Animal Number
		31649	31650	31651
1 h	ER	2^£	2	2
	ED	1	2	2
24 h	ER	2^£	2	2
	ED	3	1	2
48 h	ER	2	2	2
	ED	3	1	2
72 h	ER	2	3	2
	ED	2	1	2
Day 4	ER	4^^	4^^	3
	ED	2	2	2
Day 5	ER	4^^$	3^^$	4^^
	ED	2^+	1	2
Day 6	ER	3^^$	3^^$	3^^$
	ED	1^+	0	1^@
Day 7	ER	3^^$	1^+	1^^$
	ED	0^+	0	0^+
Day 8	ER	2^^	1^+	1^^$
	ED	0^+	0	0^+
Day 9	ER	2^&	1^@	1^@
	ED	0	0	0
Day 10	ER	1^&	1^@	0
	ED	0	0	0
Day 11	ER	1^&	0	0
	ED	0	0	0
Day 12	ER	1^&	0	0
	ED	0	0	0
Day 13	ER	1^&	0	0
	ED	1	0	0
Day 14	ER	0^&	0	0
	ED	0	0	0
* After patch removal. ^£ Yellow discoloration ^^ Eschar formation ^+ Discoloration and alopecia ^$ Skin is dry and flaky ^& Scar tissue, alopecia ^@ Hard scaly skin

Applicant's summary and conclusion

Interpretation of results:

other: EU Criteria: Category 1B: Causes sever skin burns and eye damage (H314)

Conclusions:

Under the conditions of this study, the test material is considered to be corrosive to the skin of New Zealand White Rabbits.

Executive summary:

The test material was evaluated for its potential to produce primary dermal irritation or corrosion after a single topical 4 hour application to the skin of New Zealand White rabbits, according to the standardised guidelines OECD 404 (2002) and US EPA OPPTS 870.2500 (1998), under GLP conditions. 

 

All rabbits were observed to have slight to moderate erythema and edema through the 72 hour period with eschar formation occuring by day four. Irritation and eschar formation resolved by day 11 in two rabbits but by day 14 the presence of scar tissue and alopecia was still noted in one rabbit. 

 

Under the conditions of this study, the test material is considered to be corrosive to the skin of New Zealand White Rabbits.