Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Skin Irritation: in vivo study, rabbit (HC:NZW albino), male (OECD 404, GLP): not irritating to the skin
Eye Irritation: in vivo study, rabbit (HC:NZW albino), male (OECD 405, GLP): not irritating to the eye

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:
1988-07-26 - 1988-08-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented study conducted under GLP according to OECD guideline 404 on the registered substance itself without deviations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: HC:NZW Albino
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Ltd.
- Age at study initiation: adult
- Weight at study initiation: 3.0 - 3.7 kg
- Housing: individually in wire cages Type III-high with bedding of dust-free wood granulates Type S 8/15 (Ssniff, Hoechst)
- Diet (e.g. ad libitum): Standard diet ssniff K 4 (Ssniff Spezialdiäten GmbH, Soest/Westfalen), ca. 100-120 g per animal and day, feeding once daily in the morning
- Water (e.g. ad libitum): tap water ad libitum from 7 am to 7 pm
- Acclimation period: min. 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±2°C
- Humidity (%): ca. 50%
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12 / 12, from 6 am tp 6 pm, artificial light of ca. 27 Watt/m²
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
other: paraffin oil
Controls:
other: concurrent vehicle on the alternate flank of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
- Concentration (if solution): not explicitly noted; a paste was prepared of the test item
Duration of treatment / exposure:
4 h
Observation period:
14 d
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 6cm² of the flank
- Type of wrap if used: Hansamed band aid 'hypoallergen' (Beiersdorf No. 2342), fixed with elastic adhesive bandage (Fixomull-Stretch Klebevlies, Beiersdorf No. 2039), if experimentally required, an additional fixation with Leukoplast-porös (Beiersdorf No. 1524) was done

REMOVAL OF TEST SUBSTANCE
- Washing (if done): carefully with water
- Time after start of exposure: 4h

SCORING SYSTEM: Draize-grading
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: 1h - 7d
Irritation parameter:
erythema score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: 1h - 7d
Irritation parameter:
edema score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: 1h - 7d
Irritant / corrosive response data:
Test item is not a skin irritant.
Interpretation of results:
not irritating
Conclusions:
The study was conducted under GLP according to OECD guideline 404 on the registered substance itself without deviations. The method is to be considered scientifically reasonable. Hence, the results can be considered as reliable to assess the skin irritating properties of 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl in rabbits. The substance did not provoke any reactions in the skin (erythema, edema, eschar), scoring according to Draize did not result in any score > 0 at any time point during the observation period. In consequence, the substance does not need to be regarded as skin irritant according to Regulation (EC) 1272/2008.
Executive summary:

In a primary dermal irritation study (OECD guideline 404), adult albino HC:NZW rabbits (3 males) were dermally exposed to 500 mg of 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl in paraffin oil for 4 hours to 6 cm². Animals then were observed for 14 days.  Irritation was scored by the method of Draize.

Scoring according to Draize did not result in any score > 0 at any time point during the observation period, the primary irritation index was determined to be 0.0.

In this study, 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl is not a dermal 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:
1988-07-26 - 1988-08-02
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Well-documented study conducted under GLP according to OECD guideline 404 on the registered substance itself without deviations.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
other: HC:NZW Albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Interfauna UK Ltd.
- Age at study initiation: adult
- Weight at study initiation: 3.0 - 3.5 kg
- Housing: individually in wire cages Type III-high with bedding of dust-free wood granulates Type S 8/15 (Ssniff, Hoechst)
- Diet (e.g. ad libitum): Standard diet ssniff K 4 (Ssniff Spezialdiäten GmbH, Soest/Westfalen), ca. 100-120 g per animal and day, feeding once daily in the morning
- Water (e.g. ad libitum): tap water ad libitum from 7 am to 7 pm
- Acclimation period: min. 14 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20±2°C
- Humidity (%): ca. 50%
- Air changes (per hr): ca. 10
- Photoperiod (hrs dark / hrs light): 12 / 12, from 6 am tp 6 pm, artificial light of ca. 27 Watt/m²
Vehicle:
unchanged (no vehicle)
Controls:
other: concurrent no treatment in the alternate eye of the same animals
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 100 µl (bulk volume) = ca. 40 mg
Duration of treatment / exposure:
24h
Observation period (in vivo):
21d
Number of animals or in vitro replicates:
3
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): physiological saline
- Time after start of exposure: 24h

SCORING SYSTEM: Draize / McDonald, Shadduck (aqueous humour)

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: 1h - 7d
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: 1h - 7d
Irritation parameter:
iris score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Remarks on result:
other: 1h - 7d
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
7 d
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 24h
Remarks on result:
other: 1h - 7d
Irritant / corrosive response data:
The test item is not an eye irritant.
Interpretation of results:
not irritating
Conclusions:
The study was conducted under GLP according to OECD guideline 405 on the registered substance itself without deviations. The method is to be considered scientifically reasonable. Hence, the results can be considered as reliable to assess the eye irritating properties of 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl in rabbits. The substance did not provoke any relevant or persistent reactions in the eye. The cornea, iris and conjunctivae score were determined to be 0.0 (mean of all animals). In consequence, the substance does not need to be regarded as eye irritant according to Regulation (EC) 1272/2008.
Executive summary:

In a primary eye irritation study (OECD guideline 405), 100 µl ca. 40 mg 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl (no vehicle) was instilled into the conjunctival sac of adult albino HC:NZW rabbits (3 males) for 24 hours. Eyes were washed with phys. saline. Animals then were observed for 7 days. Irritation was scored by the method of Draize.

The substance did not provoke any relevant or persistent reactions in the eye. The cornea, iris and conjunctivae score were determined to be 0.0 (mean of all animals).

In this study, 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl is not an eye irritant.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is each a GLP OECD in vivo guideline study available to cover the endpoints skin and eye irritation, both assessed with Klimisch 1. The in vivo rabbit model is the currently most suitable model to assess potential irritating effects of a substance in humans, e.g. more reliable than a single in vitro test. Also, the rabbit model tends to overestimate the potential effects in humans, which means that the obtained results may, to the maximum, overestimate the irritating properties of a substance, hence providing an additional safety factor. Both studies revealed consistently that the substance is not an irritant to either skin or eye, which supports the conclusion not to classify the substance as irritant. This conclusion is furthermore supported by the available OECD 402 study in rats; here were no signs of irritation found up to the limit dose of 2000 mg/kg bw. There is no indication that the obtained results may not be suitable to assess the irritating properties of the substance with regard to human skin and eyes.

Consequently, no datagaps were identified, the available studies suffice to cover the present irritation / corrosion endpoint.


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

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

Justification for classification or non-classification

In both studies (skin and eye irritation), no irritating effects of the substance were noted, the determined irritation scores both were 0.0 for skin and eye irritation. Hence, 12H-Dibenzo(d,g)(1,3,2)dioxaphosphocin, 4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl does not need to be classified as skin or eye irritant according to Regulation (EC) 1272/2008.