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Toxicological information

Skin irritation / corrosion

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Administrative data

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30-09-1987 until 24-11-1987
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study is GLP and according to guideline.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report Date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
yes
Remarks:
see remarks below
Principles of method if other than guideline:
Three test animals were exposed for 3 min and 1 hour durations. Since no corrosive effects were observed another group of three rabbits was exposed for 4 hours.
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The test material was supplied by sponsor, as follows:
Description :colourless liquid
Container : glass screw-top bottle
Date of arrival : 7 september 1987
Storage conditions : room temperature

For the purpose of this study the test material used as supplied.

Test material data sheet available:
Batch/Lot no. : 1/84
Chemical name: N-methyl didecylamine
Flammability: > 100 C
melting point: ~ - 10 C
Specific gravity: 800 kg/m3
Stability: Unlimited at ambient temperature
Water solubility: very low
polar organic solvent: ethanol
non polar organic solvent: vegetable oil

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Nottingham University, School of Agriculture, Sutton Bonington, Leicestershire, United Kingdom
- Age at study initiation: 12 to 16 weeks
- Weight at study initiation: 2.21 - 3.16 kg
- Housing: individually in suspended metal cage
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: minimum five days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16 - 21
- Humidity (%): 45 - 70
- Air changes (per hr): 15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 / 12

Test system

Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.5 ml
Duration of treatment / exposure:
3 minutes, 1 hour and 4 hours
Observation period:
1 hr after removal of patches and 24, 48 and 72 hours later. Additional observations were made after 7 and 14 days.
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2.5cm x 2.5 cm
- Type of wrap if used: elasticated corset (tubigrip)

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gentle swabbing with cotton wool soaked in 3% (v/v) aqueous acetic acid followed by cotton wool soaked in distilled water.
- Time after start of exposure: 3 min, 1 hr and 4 hours

SCORING SYSTEM:
- According to Draize (1959) Association of Food and Drug Officials of the United States, Austin, Texas, "The appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics", see table below.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
mean
Remarks:
all animals 4 hrs exposure
Time point:
other: 24, 48 and 72 hrs
Score:
2.5
Max. score:
4
Reversibility:
not fully reversible within: 21 days
Irritation parameter:
edema score
Basis:
mean
Remarks:
all animals 4 hrs exposure
Time point:
other: 24, 48 and 72 hrs
Score:
2.4
Max. score:
4
Reversibility:
fully reversible within: 14 days
Irritant / corrosive response data:
Three-mi nute Exposure
Very slight erythema was noted at two treated s k i n sites one hour after removal of the patches. Well-defined erythema had developed at all treated skin sites a t the 24-hour observation and well-defined or moderate t o severe erythema continued to be noted a t the 48 and 72-hour observations. Flaking, dry, - straw-col oured s k i n (possi ble hyperkeratinisation) was noted a t all treated skin s i t e s on days seven and fourteen. The reactions extended approximately 8 cm beyond one of the treated skin sites from the 72-hour observation onwards.
Very slight oedema was confined to one treated skin s i t e one hour after patch removal. Slight or moderate oedema had developed at all treated skin sites a t t h e 24-hour observation and slight oedema con-tinued to be noted at the 48 and 72-hour observations. The oedema extended beyond one treated s k i n s i t e a t the 24, 48 and 72-hour observations. No oedema was noted on days seven and fourteen.

One-hour Exposure
Very slight or well-defined erythema was noted at all treated skin sites one hour after removal of the patches. Well -defined or moderate to severe
erythema, w i t h areas of brown discolouration of the s k i n , were noted a t all treated s k i n sites at the 24, 48 and 72-hour observations. A brown dis-colouration of the skin and loss of skin suppleness were noted a t two treated s k i n sites on day seven. Flaking, dry, straw-coloured skin (possible hyperkeratinisation) was noted at the remaining treated skin site a t this time and a t all treated skin sites on day fourteen. The reactions extended approximately 8 to 10 cm beyond all treated s k i n sites during the observati on period.
Oedema, ranging from very slight to moderate was noted a t all treated skin sites one hour after patch removal. Severe oedema had developed a t all
treated s k i n sites at the 24-hour observation b u t the oedema decreased and was only slight a t the 72-hour observation. The oedema extended beyond all treated s k i n sites at the 24, 48 and 72-hour observations. No oedema was noted on days seven and fourteen.

Four-hour Exposure
The dermal reactions extended up to 8 cm beyond all treated skin sites during the observation period. Well-defined erythema was noted at at 7 treated skin sites one and 24 hours after removal of the patches. A slight haemorrhage of the dermal capillaries was noted at one treated skin site a t these observations. A brown discolouration of the s k i n was also noted at one treated skin site at the 24-hour observation. Well-defined or moderate to severe erythema was noted at all treated skin sites at the 48 and 72-hour observations. A green or brown discolouration of the skin was noted at two treated skin sites at these times, with transverse folding of the skin apparent at one treated skin site. On day seven dry, straw-coloured, flaking skin
( possi ble hyperkeratinisation) was noted at all treated skin sites. Small scattered scabs were also noted at two treated skin sites. Fissuring of the
skin, with signs of dried blood i n the fissures, was apparent at one treated skin site.
On day fourteen, glossy skin and reduced fur growth, w i t h or without desquamation, was noted at two treated s k i n sites. Fissuring, w i t h
associated small scattered scabs, and reduced fur growth were noted at the remaining treated skin site.
To establish reversibil ity of the dermal reactions an additional observation was made on day twenty-one. Glossy skin and reduced fur growth were noted at all treated skin sites. No evidence of corrosion was noted.
Slight or severe oedema was noted at all treated skin sites one hour after patch removal. Oedema ranging from very slight to moderate was noted at all treated skin sites at the 24, 48 and 72-hour observations. Very slight or slight oedema was noted at two treated skin sites on day seven. No oedema
was noted at the remaining treated skin site at this time or at any treated skin site on days fourteen or twenty-one.

Any other information on results incl. tables

Summary of dermal lesions (following 4-h application)

no.

Effect

Hour

Days after application

Mean score erythema

24/48/72 h

Mean score oedema

24/48/72 h

1

1

2

3

7

14

21

48

Erythema/ eschar

Oedema

2 R

4 R

2 BrR

3 R

3 GrRTf

3 R

3 GrRTf

3 R

HyScR

2 R

GsFrDR

0

GsFrR

0

2.7

3.0

92

Erythema/ eschar

Oedema

2 H

2 R

2 HR

3 R

3 BrR

2 R

3 BrR

2 R

HyFiScR

1 R

FrFiScR

0

GsFrR

0

2.7

2.3

110

Erythema/ eschar

Oedema

2

2

2 R

3 R

2 R

2 R

2 R

2 R

HyR

0

GsFrR

0

GsFrR

0

2.0

2.0

Mean

2.5

2.4

Fa = abnormal fur growth; Fr = reduced fur growth; D = desquamation; T = thickening of skin; R= reactions extending beyond treatment site; Hy = hyperkeratinisation; Br = brown discolourisation of skin; L = loss of skin suppleness; H = haemorrhage of dermal capillaries; Gr = green discoulorisation of skin; Tf = transverse folding of skin; Fi = fissuring of skin; Sc = small scattered scabs; Gs = glossy skin

Applicant's summary and conclusion

Interpretation of results:
Category 2 (irritant) based on GHS criteria
Remarks:
Migrated information
Conclusions:
The mean erythema and oedema score after 4 hr exposure was between 2.3 and 4.0 for two out of three animals.
Reversibility not completely shown within 21 days.
No signs of necrosis.
Executive summary:

A study was performed to assess the effects of Amine M210D on the irritancy potential to the skin of the New Zealand White rabbit. The method used was based on that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion".

A three minute, 1 hour and 4 hours, semi-occluded dermal application of the test material to the intact skin of three rabbits followed by a decontamination procedure with 3% (v/v) aqueous acetic acid followed by cotton wool in distilled water, produced irritation scores directly after patch removal and 1,2 and 3 days afterwards. The erythema/eschar effects were not fully reversible within 21 days, but the oedema effects were within 14 days. There was no evidence of visible necrosis.

The test material produced positive criteria for skin irritation following a four-hour exposure period in all rabbits.

The test material produced no evidence of visible necrosis following exposure periods of up to four hours.