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Diss Factsheets

Administrative data

Description of key information

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
Study period:
9/28/92 - 9/30/92
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This test should be used viewed on a weight of evidence approach as not OECD method. But it was completed per GLP and according to 49 Code of Federal Regulations 173:132 (USA) (US Department of Transport Protocol).
Qualifier:
according to guideline
Guideline:
other: 49 Code of Federal Regulations 173:132 (USA) (US Department of Transport Protocol).
Principles of method if other than guideline:
A single dose of 2000 mg of CP-89,575/kg was applied to an approximately 240 cm2 (15 x 16 cm) area of intact skin that was premoistened with normal saline. The test material was held in continuous contact with the skin under an occlusive dressing for 24 hours. The rabbits were observed for clinical signs of toxicity and gross skin changes at
least once daily for 2 days after dosing and were weighed daily. Each animal was identified with a unique ear tattoo number and each cage was labeled with a card containing all
pertinent study information. The animals were dosed on 9/28/92 {day 1) and euthanized by intravenous sodium pentobarbital overdose on 9/'30/92 {day 3).
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
SOURCE: Millbrook Farm
SEX: 3 Males, 2 Females
WEIGHT RANGE: 3.13 to 3.44 kg
The rabbits were observed for clinical signs of toxicity and gross skin changes at
least once daily for 2 days after dosing and were weighed daily. Each animal was identified with a unique ear tattoo number and each cage was labeled with a card containing all
pertinent study information.
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
other: The test area was pre-moistened with normal saline.
Controls:
no
Amount / concentration applied:
2000 mg
Duration of treatment / exposure:
24 h
Observation period:
2 days
Number of animals:
5
Details on study design:
A single dose of 2000 mg of CP-89,575/kg was applied to an approximately 240 cm2 (15 x 16 cm) area of intact skin that was premoistened with normal saline. The test material was held in continuous contact with the skin under an occlusive dressing for 24 hours. The rabbits were observed for clinical signs of toxicity and gross skin changes at least once daily for 2 days after dosing and were weighed daily. Each animal was identified with a unique ear tattoo number and each cage was labeled with a card containing all pertinent study information.

The animals were dosed on 9/28/92 {day 1) and euthanized by intravenous sodium pentobarbital overdose on 9/'30/92 {day 3). Doses were calculated on a weight basis (i.e., mg of compound as supplied/kg); the purity (activity) of the compound (95.6%) was not taken into consideration for dose calculations. The stability of the test article under the conditions of the study was not determined.
A standardized scoring system was used to evaluate skin changes at the application site. Draize scoring. (Draize, J. H., Woodard, G., and Calvery, H. 0.: Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes.J. Pharmacol. Exptl. Therap., 82:3n - 390, 1944)

Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 72 hours
Score:
0
Max. score:
0
Irritant / corrosive response data:
SKIN CHANGES: No erythema, edema, or other signs of skin irritation were noted in any of the rabbits during the observation period (72 hours)
Other effects:
CLINICAL OBSERVATIONS: All rabbits remained asymptomatic during the test period, and there was no effect on food consumption or body weight.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Results of this test indicate that because no signs of skin irritation were produced, CP-89,575 is not considered a an irritant.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9/28/92 - 9/30/92
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study followed FHSA Guidelines, CFR Title 16, Section 1500.42 (US Federal Hazardous Substances Act). Study was conducted according to GLP.
Qualifier:
according to guideline
Guideline:
other: FHSA Guidelines, CFR Title 16, Section 1500.42 (US Federal Hazardous Substances Act).
Principles of method if other than guideline:
A representative sample of test material (26.6 mg), equivalent to a volume of approximately 0.1 ml of CP-89,575 powder, was introduced into the conjunctival sac of the left eye; the right eye of each animal served as an untreated control. The treated eye of each rabbit was not rinsed after dosing. The animals were observed for clinical signs for 4 days and were weighed daily. On the day of dosing (day 1), the eyes were evaluated with minimal manipulation and without the use of fluorescein. Eyes were also evaluated 24, 48, and 72 hours after dosing.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
SPECIES: Albino Rabbit (New Zealand White)
SOURCE: Millbrook Farm
SEX: 1 Male, 2 Females
WEIGHT RANGE: 2.86 to 3.02 kg


Vehicle:
not specified
Controls:
other: Untreated right eye was used as control
Amount / concentration applied:
26.2 MG
Duration of treatment / exposure:
72 hours
Observation period (in vivo):
The animals were observed for clinical signs for 4 days and were weighed daily. On the day of dosing (day 1), the eyes were evaluated with minimal manipulation and without the use of fluorescein. Eyes were also evaluated 24, 48, and 72 hours after dosing
Number of animals or in vitro replicates:
3
Details on study design:
The animals were dosed on 10/14/92 and euthanized by intravenous sodium pentobarbital overdose on 10/17/92. The purity (activity) of the compound (95.6%) was not taken into consideration, and the stability of the test article under the conditions of the study was not determined.
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0.33
Irritation parameter:
conjunctivae score
Remarks:
(redness)
Max. score:
1
Remarks on result:
other: Max. duration: 2 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
chemosis score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
chemosis score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
chemosis score
Max. score:
0
Remarks on result:
other: Max. duration: 0 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
cornea opacity score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 73 hrs
Score:
0
Irritation parameter:
cornea opacity score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
cornea opacity score
Max. score:
0
Remarks on result:
other: Max. duration: 0 h; Max. value at end of observation period: 0 (related to all animals)
Irritation parameter:
iris score
Basis:
animal #1
Remarks:
(mean score 1)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #2
Remarks:
(mean score 2)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
iris score
Basis:
animal #3
Remarks:
(mean score 3)
Time point:
other: overall at 24, 48 and 72 h
Score:
0
Irritation parameter:
iris score
Max. score:
0
Remarks on result:
other: Max. duration: 0 h; Max. value at end of observation period: 0 (related to all animals)
Irritant / corrosive response data:
At 2 hours after dosing. a small amount of what appeared to be the test article, slight reddening (score= 1) of the palpebral conjunctivae, and slight chemosis (score= 1) were apparent in the treated eye of each animal. In addition, a small amount of discharge (score
= 1) was evident in the treated eye of Rabbit #2 and 3.

By 4 hours after dosing, slight circumcomeal reddening was apparent in each of the treated eyes, the degree of conjunctiva! reddening in Rabbit #3 had increased (score= 2), and the discharge in the eye of Rabbit #2 had subsided.


At 24 hours after dosing, the treated eye of two of the three rabbits(# 1 and 2) appeared essentially normal, while only slight reddening of the conjunctivae (score = 1) and slight
circumcorneal reddening were noted in the other animal. The integrity of the corneal epithelium was confirmed at 24 hours with the aid of fluorescein. When examined at 48 and 72 hours after dosing, each of the treated eyes appeared normal.


Other effects:
The untreated control eye of each animal was normal and unchanged throughout the test period.
All rabbits remained asymptomatic during the test period, and there was no effect on food consumption or body weight
Interpretation of results:
other: not classified
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The results of this study indicate that CP-89,575 is not an ocular irritant in albino rabbits when tested according to FHSA guidelines (16 CFR 1500.42) because a positive reaction was not apparent in any of the treated eyes 24, 48, or 72 hours after the instillation of a single dose of 26.6 mg of the compound.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

Justification for selection of skin irritation / corrosion endpoint:

No irritation observed in any animals

Justification for selection of eye irritation endpoint:

No signficant irritation observed in any animals

Justification for classification or non-classification

No signficant irriation observed in either a skin or eye irritation test.