Registration Dossier

Administrative data

Description of key information

In vitro and and in vivo O.E.C.D. test guideline 404 and 405 studies were conducted to access the test substances potential to cause skin and eye irritation/corrosion.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the O.E.C.D. test guideline 404 with GLP compliance.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
The rabbits were acquired from Rich-Glo II, Inc. Wills Point, Texas and weighted 2.72-4.0 kg at study initiation. The study animals were housed in suspended, wire bottom, stainless steel cages, 1 per cage. The animals were keept in an animal room that maintained a temperature of 18-22°C and a relative humidity 46-98%. The animal room had a 12-hour light/dark cycle and 10-12 air changes/hour The rabbits were allowed PMI Feeds, Inc.TM Lab Rabbit Diet #532 1 ~ 8 oz. daily and Municipal water supply analyzed by TCEQ Water Utilities Division; available ad libitum from automatic water system.







Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5 mL undiluted.
Duration of treatment / exposure:
4 hours
Observation period:
14 days.
Number of animals:
4
Details on study design:
Each animal was prepared on the day prior to treatment by clipping the dorsal area of the trunk free of hair to expose an area at least 8 x 8 cm. On Day 0, 0.5 mL of the undiluted test substance was applied to each test site and covered with a 4 ply, 2.5 x 2.5 cm surgical gauze patch. Each patch was secured in place with a strip of non-irritating adhesive tape. The entire trunk of each animal was loosely wrapped with a semi-permeable dressing (orthopedic stockinette) which was secured on both edges with strips of tape to retard evaporation of volatile substances and to prevent possible ingestion of the test substance.

After four hours, the patches and wrappings were removed. The test sites were gently washed with room temperature tap water and a clean cloth to remove as much residual test substance as possible. The test sites were observed for erythema and edema formation, and any other dermal defects or irritation at 1, 24, 48 and 72 hours, and on Days 7, 10 and 14 after unwrap (day of treatment is Day 0).

Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 72 hours
Score:
ca. 3.4
Reversibility:
not reversible
Remarks on result:
other: Evidence of skin corrosion was observed in 2/4 of the animals and was not reversible by day 14.
Irritant / corrosive response data:
Very slight to severe erythema and very slight to moderate edema were present for each animal at each observation through Day 14. Other signs of irritation included coriaceousness, desquamation, eschar, discoloration and necrosis.
Interpretation of results:
corrosive
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance is considered to be corrosive to rabbit skin under the conditions of the study. 2/4 animals placed on study exhibited eschar and necrosis at the site of treatment that was not reversible by 14 days.
Executive summary:

The test substance, Formaldehyde, polymer with 1,3 -benzenedimethanamine and phenol was accessed for skin irritation/corrosion potential in an O.E.C.D. test guideline 404 study. The test substance is considered to be corrosive to rabbit skin under the conditions of the study. 2/4 animals placed on study exhibited eschar and necrosis at the site of treatment that was not reversible by 14 days.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (corrosive)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted according to the O.E.C.D. test guideline 405 with GLP compliance.
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
The rabbits were acquired from Rich-Glo II, Inc; Wills Point, Texas and weighed approximately 3.5 kilograms at study initiation. The animals were housed in suspended, wire bottom, stainless steel cages, 1 per cage. The animal room was maintained at 19-23°C with a relative humidity of 37-96% and a 12-hour light/dark cycle with 10-12 air changes/hour. The animals were provided PMI Feeds, Inc.°’ Lab Rabbit Diet #532 1. ~8 oz. dailyand Municipal water supply analyzed by TCEQ Water Utilities Division; available ad libitum from automatic water system.




Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.1 mL undiluted
Duration of treatment / exposure:
24 hours
Observation period (in vivo):
21 days
Number of animals or in vitro replicates:
One
Details on study design:
Only one animal was placed on study due to the apparent corrosive nature of the test substance and a measured pH of 11.0. On Day 0, a dose of 0.1 mL of the undiluted test substance was placed into the conjunctival sac of the right eye of the animal by gently pulling the lower lid away from the eyeball to form a cup into which the test substance was dropped. Prior to dosing, both eyes were anesthetized with Tetracaine ophthalmic solution . The lids were gently held together for one second to prevent loss of material. The untreated left eye served as a comparative control.

The treated eye was examined without magnification under white room lighting provided by daylight-type fluorescent ceiling fixtures, and (if needed) an additional source of white light affixed to the examination table or using a handheld flashlight. The grades of ocular reaction were recorded at 1,24, 48 and 72 hours, and at 4, 7, 10, 14, 17 and 21 days after treatment. The cornea of the treated eye was examined immediately after the
24-hour observation with a fluorescein sodium ophthalmic solution. A Finoff ocular transilluminator with cobalt blue filter was utilized to enhance visualization of fluorescein staining. Since the cornea exhibited fluorescein staining at the 24-hour observation, it was re-examined with the fluorescein sodium ophthalmic solution at each consecutive observation until fluorescein staining of the cornea no longer occurred. The treated eye was washed with room temperature DI water for one minute immediately after recording the 24-hour observation.

Irritation parameter:
maximum mean total score (MMTS)
Basis:
animal #1
Time point:
other: 14 days
Score:
ca. 88
Max. score:
88
Reversibility:
not reversible
Remarks on result:
other: Corneal opacity and area reached a maximum of 4 at day 14. Fluorescein staining was observed at 24 hours after treatment and persisted through Day 21 after treatment.
Irritant / corrosive response data:
The maximum average irritation score of 88 0, obtained 14 days after treatment, was used to rate the test substance extremely irritating. Fluorescein staining was observed at 24 hours after treatment and persisted through Day 21 after treatment. Maximum corneal opacity of grade 4 was oberved on days 14, 17 and 21. Maximum corneal area involvement was observed on post treatment days: 1, 2, 3, 4, 10 and 14.
Interpretation of results:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The test substance is judged to be Extremely irritating/corrosive to the rabbit eye based on the outcome of one animal.
Executive summary:

The test substance, Formaldehyde, polymer with 1,3 -benzenedimethanamine and phenol was evaluated for eye irritation potential in an O.E.C.D. test guideline 405 study with one animal. The test substance is judged to be Extremely irritating/corrosive to the rabbit eye based on the outcome of the one animal.

 

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The test substance, Formaldehyde, polymer with 1,3 -benzenedimethanamine and phenol was judged to be corrosive to rabbit skin in two animals within 4 hours of exposure. Extreme eye iritation based on corneal damage was observed in one rabbit placed on study. The corneal damage/opacity was not reversible within 21 days of treatment.


Justification for selection of skin irritation / corrosion endpoint:
In vivo rabbit study results document skin corrosion.

Justification for selection of eye irritation endpoint:
In vivo rabbit study results document extreme irritation/corrosion to the eye.

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Justification for classification or non-classification

Based on in vivo rabbit study findings the test substance, Formaldehyde, polymer with 1,3 -benzenedimethanamine and phenol is CLP Category Corrosive 1C, Danger, H314, "Causes severe skin burns and eye damage". Under the DSD the test substance is R34, "Causes burns".