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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:
01 June 2009 to 24 September 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Study was conducted and reported in accordance with international test guidelines.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
US EPA Certificate

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
Identity: Hexahydro-1,3,5-trimethyl-s-triazineDate Received: 26 May 2009Storage Room temperature and humidityDescription: Light gold liquidSample Preparation: The test item was used as rceived

Test animals

Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
Animals were received from Covance Research Products Inc., Denver, PA on 18 March 2009. Following an acclimation period of at least five days, one health New Zealand White rabbit (female) was selected from a larger group without conscious bias.The animal was born on 29 November 2008. The pretest body weight was 3.6 kg.The animal was identified by cage notation and a uniquely numbered metal ear tag and individually housed in a suspended cage. Paper bedding was was placed beneath the cage and changed at least three times per week. Fresh PMI rabbit chow (Diet #5321) was provided daily. Water was available ad libitum. The animal room was temperature controlled, had a 12 hour light: 12 hour dark photoperiod.The temperature range of the animal room was 65.6 - 76.5 degrees farenheit and the relative humidity was 48.6 to 99.5 %.

Test system

Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 ml per site at 3 sites.- Concentration (if solution): 32.99 % test item in water.
Duration of treatment / exposure:
The dressing and test article patch covering site #1 were removed at 3 minutes postdose, over site #2 at 1 hour postdose and the torso wrappings and patch covering site #3 at 4 hours postdose.
Observation period:
The test sites (#1, 2 and 3) were scored for dermal irritation at 60 minutes after removal of wrappings. Site #3 (4-hour exposure) was scored at 24, 48 and 72 hours and again on days 7 and 14. Erythema and edema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.Body weight was recorded pretest, 72 hours and termination. The general health of the animal was monitored at each observation point.
Number of animals:
One animal was used for this study.
Details on study design:
Site PreparationThe day prior to the application of the test item, the dorsal area of the trunk of the animal was clipped free of hair. The dose sites were approximately 3 x 3 cm.DosingInitially, one rabbit was dosed sequentially on sites #1, 2, and 3. The test item was dosed at 0.5 ml/site and placed under a 2.5 x 2.5 cm, 4 ply surgical gauze patch. Gentle pressure was applied to aid in the distribution of the test item over the contact site. The rabbit was gently held in place and a piece of porous dressing was secured with non-irritating tape over dose site #1 (semi-occlusive) for the 3 minute exposure period. The torso was covered with a piece of porous dressing large enough to cover dose sites #2 and 3 with at least 5 cm square to spare on on all sides of the gauze patch. Porous, non-irritating tape was used to encircle the trunk of the animal.The dressing and test article patch covering site #1 was removed at 3 minutes post-dose, over site #2 at 1 hour postdose and the torso wrappings and patch covering site #3 at 4 hours postdose. All sites were gently washed with distilled water to remove residual test material.Following the 72 hour observation the severity of the scores meant that no further animals were added to the study for ethical reasons. The initial animal was extended to day 14.Observation MethodErythema and edema were scored according to the numerical Draize technique. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction. Additional signs were described.ErythemaNo erythema: 0Very slight erythema (barely perceptible): 1Well defined erythema: 2Moderate to severe erythema: 3Severe erythema (beet redness) to slight eschar formation (injuries in depth): 4EdemaNo edema: 0Very slight edema (barely perceptible): 1Slight edema (edges of area well-defined by definite raising): 2Moderate edema (raised approximately 1.0 mm): 3Severe edema (raised more than 1.0 mm, extending beyond the area of exposure): 4

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
3 min exposure
Time point:
other: 60 Minutes
Score:
0
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
60 minute exposure
Time point:
other: 60 minutes
Score:
0
Reversibility:
no data
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 60 minutes
Score:
2
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 24 hours
Score:
3
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 48 hours
Score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 72 hours
Score:
4
Reversibility:
not fully reversible within: 14 days
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 7 days
Score:
> 4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: necrosis and pale areas also observed
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 14 days
Score:
> 4
Reversibility:
not fully reversible within: 14 days
Remarks on result:
other: Necrosis also observed
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
3 min exposure site
Time point:
other: 60 minutes
Score:
0
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
1 hour exposure site
Time point:
other: 60 minutes
Score:
1
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 60 minutes
Score:
3
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 24 hours
Score:
2
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 48 hours
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 72 hours
Score:
1
Reversibility:
fully reversible within: 7 days
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 7 days
Score:
0
Reversibility:
no data
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
4 hour exposure site
Time point:
other: 14 days
Score:
0
Reversibility:
no data
Irritant / corrosive response data:
Results presented above.
Other effects:
No systemic effects were observed during this study. Body weight changes were normal.

Applicant's summary and conclusion

Interpretation of results:
Category 1 (corrosive) based on GHS criteria
Remarks:
Migrated information
Conclusions:
Hexahydro-1,3,5-trimethyl-s-triazine is corrosive.
Executive summary:

Objective: To determine the irritant or corrosive effects, if any, of hexahydro-1,3,5 -trimethyl-s-triazine when applied dermally. This study was conducted in accordance with OECD Guideline 404 "Acute Dermal Irritation/Corrosion".

Method synopsis: Since the test item was suspected to be a dermal irritant, one health female New Xealand White rabbit was dosed dermally. The test item (0.5 ml) was applied dermally to three intact sites for an exposure period of 3 minutes on site #1, 1 hour on site #2 and 4 hours on site #3. Erythema and edema were scored at 60 minutes after each patch removal on all three sites. Site #3 was scored again at 24, 48 and 72 hours and again on days 7 and 14. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Following the 72 hour observation, the severity of the scores resulted in no further animals being added to the study. The initial animal was extended to day 14. Body weight was recorded pretest, 72 hours and at test termination.

Summary:

3 minute exposure: There were no erythema or edema observed at 60 minutes after patch removal following the 3 minute exposure.

1 hour exposure: There was no erythema and very slight edema at 60 minutes following the 1 hour exposure.

4 hour exposure: Erythema was well defined and edema was moderate at 60 minutes following the 4 hour exposure. Erythema was moderate to severe at 24 hours and severe (with no eschar formation observed) at 48 and 72 hours. By day 7, the dose site was necrotic with pale areas and necrotic on day 14. Edema was slight at 24 hours and very slight at 48 and 72 hours. By days 7 and 14, edema was absent.

Systemic Observations: There were no abnormal physical signs noted during the observation period.

Body weight changes were normal.

Conclusion: Hexahydro-1,3,5 -trimethyl-s-triazine is corrosive.