Registration Dossier

Administrative data

Description of key information

In the key skin and eye irritation studies (Toxikon Corporation, 1990b and c, respectively), which were conducted using protocols comparable with OECD 404 and 405, respectively, and to GLP, it was concluded that D5 was not irritating to the skin or eyes of rabbits.

There are no studies specific to testing for respiratory tract irritation; however, acute inhalation (RCC Ltd, 1994) and repeated dose inhalation studies, including the key study (RCC Ltd, 2005) generally show signs of respiratory tract irritation.

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:
No data
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
Federal Hazardous Substance Act Regulations - Consumer Product Safety Commission, 16 CFR, Part 1500, Chapter II, Subpart C, Section 1500.41, 1988.
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS

- Source: Eastern Rabbit Breeding Industry, Taunton, MA

- Age at study initiation: 11 weeks

- Weight at study initiation: 2-3kg

- Housing: Individually housed in suspended stainless steel cages, with hardwood chips as non-contact bedding under the cages.

- Diet: commercial rabbit ration, ad libitum

- Water: municipal water, ad libitum

- Acclimation period: upon receipt, animals were placed in quarantine for 3 days.


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68 +/- 3

- Humidity (%): 30-70

- Air changes (per hr): minimum 10-13

- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: shaved and abraded sites tested independently
Vehicle:
unchanged (no vehicle)
Controls:
other: Each animal served as its own control.
Amount / concentration applied:
TEST MATERIAL

- Concentration (if solution): Undiluted

Duration of treatment / exposure:
24 hour(s)
Observation period:
The animals were observed for signs of erythema and edema at 24 and 72 hours post application of the test substance.
Number of animals:
3M, 3F
Details on study design:
TEST SITE

- Area of exposure: dorsal skin

- Type of wrap if used: gauze patch, which was held in place with Vetrap bandaging. the patches were applied to one intact site and one abraded site per animal.


REMOVAL OF TEST SUBSTANCE

- Washing (if done): The skin was wiped and rinsed with USP water for injection following the exposure period to remove remaining test article.

- Time after start of exposure: 24 hours


SCORING SYSTEM: Draize
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 24/72h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No overt signs of toxicity were evident in any of the animals during the course of the study. No signs of erythema or edema formation were evident on the test (or control) sites of any animal at any of the observation periods, whether the skin was abraded or intact.
Other effects:
All of the test animals exhibited a gain in body weight during the study.

The test article is considered non-irritating to the skin of the test animals.

Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to not be irritating to rabbit skin in a reliable study conducted according to an appropriate test protocol.
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Principles of method if other than guideline:
Federal Hazardous Substance Act Regulations - Consumer Product Safety Commission, 16 CFR, Part 1500, Chapter II, Subpart C, Section 1500.42, 1988
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS

- Source: Eastern Rabbit Breeding Industry, Taunton, MA

- Age at study initiation: young adults

- Weight at study initiation: 2-3kg

- Housing: Individually housed in suspended stainless steel cages, with hardwood chips as non-contact bedding under the cages.

- Diet: commercial rabbit ration, ad libitum

- Water: municipal water, ad libitum

- Acclimation period: upon receipt, animals were placed in quarantine for 7 days.


ENVIRONMENTAL CONDITIONS

- Temperature (°F): 68 +/- 3

- Humidity (%): 30-70

- Air changes (per hr): minimum 10-13

- Photoperiod (hrs dark / hrs light): 12/12


Vehicle:
unchanged (no vehicle)
Controls:
other: Untreated eye.
Amount / concentration applied:
TEST MATERIAL

- Amount(s) applied (volume or weight with unit): 0.1 ml
Duration of treatment / exposure:
24 hour(s)
Observation period (in vivo):
Eyes were examined at 24, 48 and 72 hours after treatment.
Number of animals or in vitro replicates:
3M, 3F
Details on study design:
REMOVAL OF TEST SUBSTANCE

- Washing (if done): not rinsed


SCORING SYSTEM: Draize


TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 24/48/72h
Score:
0
Max. score:
0
Reversibility:
other: no effects
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
iris score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
conjunctivae score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
3
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritation parameter:
chemosis score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
4
Remarks on result:
no indication of irritation
Irritant / corrosive response data:
No overt signs of toxicity were evident during the course of the study in any of the animals. No macroscopic alterations to the cornea, iris, or conjunctiva were evident in the treated eyes of any of the test animals. No evidence of irritation was noted in the control eyes at any observation points.
Other effects:
All animals exhibited an increase in body weight during the course of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The test material was determined to not be irritating in a reliable study conducted according to an appropriate test protocol and in compliance with GLP.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Additional information

The key skin irritation study was conducted according to OECD test guideline 404. New Zealand white rabbits (3 animals/sex) were dermally exposed to undiluted D5 under a semi-occlusive dressing for 24 hours. On each animal there was one intact application site and one abraded site. The animals were observed for signs of erythema and edema at 24 and 72 hours post application of the test substance. Throughout the test, animals were observed for signs of toxicity. Skin reactions were graded according to the Draize grading system. There were no signs of toxicity or irritation and animals gained weight as expected. There are two reliable supporting studies (Proctor & Gamble, 1985; Unknown, 1975) available for skin irritation, which confirm the conclusion that D5 is not irritating to skin.

The key eye irritation study was conducted according to OECD test guideline 405. New Zealand white rabbits (3 animals/sex) had 0.1 ml undiluted D5 instilled into one of their eyes. Eyes were examined at 24, 48 and 72 hours after treatment. Animals were also observed for signs of toxicity throughout the test. No overt signs of toxicity were evident during the course of the study in any of the animals. No macroscopic alterations to the cornea, iris, or conjunctiva were evident in the treated eyes of any of the test animals. No evidence of irritation was noted in the control eyes at any of the observation points. There are two reliable supporting studies (Carnegie-Mellon, 1976; Springborn Institute for Bioresearch, Inc, 1977) available for eye irritation, which confirm the conclusion that D5 is not irritating to eyes.


Justification for classification or non-classification

Based on the available data D5 does not require classification for skin and eye irritation according to Regulation (EC) No. 1272/2008.