Registration Dossier

Administrative data

Description of key information

SKIN
Not irritating, rabbit; OECD 404 and EPA OPPTS 870.2500
EYE
Not irritating, rabbit; OECD 405 and EPA OPPTS 870.2400

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: GLP compliant, OECD Guideline study performed without deviations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
Deviations:
no
GLP compliance:
yes
Remarks:
US EPA TSCA GLPs (40 CFR, Part 792); OECD GLPs
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Details on test animals and environment: Two male and one female (nulliparous and non-pregnant) New Zealand White rabbits, at least 10 weeks of age, weighing 2.09 to 2.26 kg were obtained from the supplier. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages with hardwood chips for bedding. They were provided food and tap water ad libitum. Room temperature was 68 ± 5 °F and the relative humidity ranged between 30 - 70 %. Room lights were on a 12-hour light/dark cycle.
Type of coverage:
semiocclusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
Approximately 0.5 gram of the test substance was applied to a small area of the skin (approximately 6 cm²).
Duration of treatment / exposure:
4 hour exposure period
Observation period:
Test sites were observed for signs of erythema and oedema 1, 24, 48 and 72 hours after patch removal. Daily clinical observations included all toxicologic and pharmacologic signs.
Number of animals:
3
Details on study design:
Approximately 24 hours prior to dosing, the application sites were prepared by clipping the skin of the trunk free of hair (not less than 10 % of the body surface was clear for the application of the test substance). Approximately 0.5 gram of the test substance was applied to a small area of the skin (approximately 6 cm²). The application site was covered with a gauze patch and secured with non-irritating tape. The test was conducted with 3 animals, each receiving one patch for an exposure period of 4 hours. Test sites were observed for signs of erythema and oedema 1, 24, 48 and 72 hours after patch removal. Daily clinical observations included all toxicologic and pharmacologic signs. Animals were weighed on Day 0 (prior to dose administration) and at the end of the observation period (Day 3). All animals were euthanised with an injectable barbiturate after body weight collection on Day 3 and discarded without further evaluation.
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 72
Score:
0
Reversibility:
other: not applicable
Irritant / corrosive response data:
No signs of erythema or edema were present at any of the test or control sites at any of the observation periods.
Other effects:
All animals gained weight over the course of the study. No overt signs of toxicity were evident in any of the animals during the course of the study.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, DMBPC is considered to be a non-irritant.
Executive summary:

The irritation potential of the test material was investigate din accordance with the standardised guidelines OECD 404 and EPA OPPTS 870.2500 under GLP conditions.

The shaved skin of 3New Zealand White rabbits was exposed to the test material in a semi-occlusive fashion for 4 hours. Approximately 0.5 gram of the test substance was applied to a small area of the skin (approximately 6 cm²). 

Test sites were observed for signs of erythema and oedema 1, 24, 48 and 72 hours after patch removal. Daily clinical observations included all toxicologic and pharmacologic signs. 

Animals were weighed on Day 0 (prior to dose administration) and at the end of the observation period (Day 3). All animals were euthanised with an injectable barbiturate after body weight collection on Day 3 and discarded without further evaluation.

No signs of erythema or oedema were present at any of the test or control sites at any of the observation periods.

All animals gained weight over the course of the study. No overt signs of toxicity were evident in any of the animals during the course of the study.

Under the conditions of this study, DMBPC is considered to be a non-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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP compliant, OECD Guideline study performed without deviations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes
Remarks:
US EPA TSCA GLPs (40 CFR, Part 792) and OECD GLPs
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Two male and two female (nulliparous and non-pregnant) New Zealand White rabbits, at least 10 weeks of age, weighing 2.12 to 2.24 kg were obtained from the supplier. The animals were acclimated for at least five days and individually housed in suspended stainless-steel cages with hardwood chips for bedding. They were provided food and tap water ad libitum. Room temperature was 68 ± 5 °F and the relative humidity ranged between 30 - 70 %. Room lights were on a 12-hour light/dark cycle.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
0.1 mL (~50 mg)
Duration of treatment / exposure:
The test substance was instilled into the left eye by gently pulling the lower lid away from the eye to form a cup into which the test substance was placed. The upper and lower lids were gently held together for approximately one second to prevent the loss of the test substance. The eyes of the test animals were not rinsed at any time following test substance application.
Observation period (in vivo):
The eyes were examined at 1, 24, 48 and 72 hours after treatment
Number of animals or in vitro replicates:
4 (1 preliminary and 3 main test animals)
Details on study design:
Within the 24 hours prior to dosing, the eyes of the animals selected for the test were examined to ensure that the eyes were free of abnormality, damage and disease, scored according to the Grades for Ocular Lesions and scored by Fluorescein Staining (details provided below). An initial procedure using a 10 % dilution of the test substance was performed on one animal. No irritation of the treated eye was observed and the study proceeded with the dosing of 3 additional animals with the neat test substance.

The animals were dosed in the left eye at a volume of 0.1 mL (~50 mg). The test substance was instilled into the left eye by gently pulling the lower lid away from the eye to form a cup into which the test substance was placed. The upper and lower lids were gently held together for approximately one second to prevent the loss of the test substance. The eyes of the test animals were not rinsed at any time following test substance application. The right eye remained untreated and served as a control. The eyes were examined at 1, 24, 48 and 72 hours after treatment and scored according to the Grades for Ocular Lesions provided below. In addition, after recording the scores at 24 hours, the eyes were further examined with the aid of fluorescein to further characterise corneal opacity. Evaluation of the eyes was facilitated by the use of a hand-held slit lamp. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start (Day 0) and completion (Day 3).
Irritation parameter:
conjunctivae score
Basis:
mean
Remarks:
of the three animals
Time point:
other: 72 hours
Score:
0
Max. score:
20
Remarks on result:
other: total conjunctiva score = redness score + chemosis score x 2
Irritation parameter:
iris score
Basis:
mean
Remarks:
of the three animals
Time point:
other: 72 hours
Score:
0
Max. score:
10
Remarks on result:
other: total iris score = iris score x 5
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of the three animals
Time point:
other: 72 hours
Score:
0
Max. score:
80
Remarks on result:
other: total cornea score = opacity score + area score x 5
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #1
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: total conjunctiva score = 2 (redness + chemosis x 2)
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #2
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: total conjunctiva score = 2 (redness + chemosis x 2)
Irritation parameter:
conjunctivae score
Remarks:
redness
Basis:
animal #3
Time point:
other: 1 hour
Score:
1
Max. score:
3
Reversibility:
fully reversible within: 24 hours
Remarks on result:
other: total conjunctiva score = 2 (redness + chemosis x 2)
Irritant / corrosive response data:
No corneal or iridial involvement was observed in the test eyes of any animal at any time point. All three animals demonstrated mild conjunctival redness at the 1-hour scoring interval which resolved by the 24-hour observation period. No fluorescein staining was present in the test eyes at any time point during the study.
Other effects:
All animals gained weight and no systemic signs of toxicity were observed during the course of the study. No irritation was observed in the control eyes at any scoring interval.

Table 1: Results 

Summary of Results for the Treated (Left) Eyes

Animal No.

Effects at 1 hour

Cornea

Iris

Conjunctiva

Fluor Exam

O

A

V

R

C

IS

A

10611

0

0

0

1

0

n/a

n/a

10612

0

0

0

1

0

n/a

n/a

10613

0

0

0

1

0

n/a

n/a

Effects at 24 hours

10611

0

0

0

0

0

n/a

n/a

10612

0

0

0

0

0

n/a

n/a

10613

0

0

0

0

0

n/a

n/a

Effects at 48 hours

10611

0

0

0

0

0

0

0

10612

0

0

0

0

0

0

0

10613

0

0

0

0

0

0

0

Effects at 72 hours

10611

0

0

0

0

0

0

0

10612

0

0

0

0

0

0

0

10613

0

0

0

0

0

0

0

O: Opacity; A: Area Involved

V: Iritis Value

R: Redness; C: Chemosis;

Fluor: Fluorescein; IS: Intensity of staining; A: Area Involved

n/a: not applicable

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of this study, DMBPC is considered to be not irritating.
Executive summary:

The irritation potential of the test material was investigate din accordance with the standardised guidelines OECD 405 and EPA OPPTS 870.2400 under GLP conditions.

Test substance (0.1 mL, ~50 mg) was instilled into the left eye of 3 New Zealand White rabbits. The eyes of the test animals were not rinsed at any time following test substance application. The right eye remained untreated and served as a control. The eyes were examined at 1, 24, 48 and 72 hours after treatment. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start (Day 0) and completion (Day 3).   

No corneal or iridial involvement was observed in the test eyes of any animal at any time point. All three animals demonstrated mild conjunctival redness at the 1-hour scoring interval which resolved by the 24-hour observation period. No fluorescein staining was present in the test eyes at any time point during the study. All animals gained weight and no systemic signs of toxicity were observed. No irritation was observed in the control eyes at any scoring interval.

Under the conditions of this study, DMBPC is considered to be not irritating.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin

The irritation potential of the test material was investigated in accordance with the standardised guidelines OECD 404 and EPA OPPTS 870.2500 under GLP conditions.The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

The shaved skin of 3New Zealand White rabbits was exposed to the test material in a semi-occlusive fashion for 4 hours. Approximately 0.5 gram of the test substance was applied to a small area of the skin (approximately 6 cm²). 

Test sites were observed for signs of erythema and oedema 1, 24, 48 and 72 hours after patch removal. Daily clinical observations included all toxicologic and pharmacologic signs. 

Animals were weighed on Day 0 (prior to dose administration) and at the end of the observation period (Day 3). All animals were euthanised with an injectable barbiturate after body weight collection on Day 3 and discarded without further evaluation.

No signs of erythema or oedema were present at any of the test or control sites at any of the observation periods.

All animals gained weight over the course of the study. No overt signs of toxicity were evident in any of the animals during the course of the study.

Under the conditions of this study, DMBPC is considered to be a non-irritant.

 

Eye

The irritation potential of the test material was investigate din accordance with the standardised guidelines OECD 405 and EPA OPPTS 870.2400 under GLP conditions.The study was awarded a reliability score of 1 in accordance with the criteria set forth by Klimisch et al. (1997).

Test substance (0.1 mL, ~50 mg) was instilled into the left eye of 3 New Zealand White rabbits. The eyes of the test animals were not rinsed at any time following test substance application. The right eye remained untreated and served as a control. The eyes were examined at 1, 24, 48 and 72 hours after treatment. Animals were observed daily for clinical signs of toxicity. Animals were weighed at study start (Day 0) and completion (Day 3).   

No corneal or iridial involvement was observed in the test eyes of any animal at any time point. All three animals demonstrated mild conjunctival redness at the 1-hour scoring interval which resolved by the 24-hour observation period. No fluorescein staining was present in the test eyes at any time point during the study. All animals gained weight and no systemic signs of toxicity were observed. No irritation was observed in the control eyes at any scoring interval.

Under the conditions of this study, DMBPC is considered to be not irritating.


Justification for selection of skin irritation / corrosion endpoint:
Only one study available.

Justification for selection of eye irritation endpoint:
Only one study available.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to irritation / corrosion.