4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2015-06-17 - 2015-07-01

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

GLP OECD 402 guideline study without deviations on the registered substance itself.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

OECD Guideline for the Testing of Chemicals No. 402 “Acute Dermal Toxicity” (adopted 24 February 1987)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Version / remarks:

Method B3 Acute Toxicity (Dermal) of Commission Regulation (EC) No. 440/2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Department of Health of the Government of the United Kingdom

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin

EC Number:

277-633-6

EC Name:

4,8-dicyclohexyl-6-hydroxy-2,10-dimethyl-12H-dibenzo[d,g][1,3,2]dioxaphosphocin

Cas Number:

73912-21-7

Molecular formula:

C27H35O3P

IUPAC Name:

7,13-dicyclohexyl-5,15-dimethyl-9,11-dioxa-10-phosphatricyclo[10.4.0.0³,⁸]hexadeca-1(12),3(8),4,6,13,15-hexaen-10-ol

Test material form:

solid: pellets

Details on test material:

- Substance type: pure substance
- Storage condition of test material: approximately 4 °C in the dark over silica gel

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Five male and five female Wistar (RccHan:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK.
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: At least 200 g, the weight variation did not exceed ±20% of the mean weight for each sex.
- Fasting period before study: no
- Housing: The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24 Hour exposure period and in groups of five, by sex, for the remainder of the study.
- Diet (e.g. ad libitum): 2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light (06:00 to 18:00) and 12 hours darkness

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

arachis oil

Remarks:

arachis oil BP

Details on dermal exposure:

TEST SITE
- Area of exposure: back and flanks
- % coverage: approx. 10% of the total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP
- Time after start of exposure: 24h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes, the test item was ground to a fine powder using a mortar and pestle, then weighed out according to each animal’s individual body weight and moistened with arachis oil BP prior to application

Duration of exposure:

24h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing and subsequently once daily for 14 days. Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, other: evidence of primary irritation

Statistics:

An estimate of the acute dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: There were no deaths.

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: There were no deaths.

Mortality:

There were no deaths.

Clinical signs:

other: No signs of systemic toxicity were noted during the observation period.

Gross pathology:

No abnormalities were noted at necropsy.

Other findings:

- Other observations: Dermal Reactions: There were no signs of dermal irritation.

Any other information on results incl. tables

Tables for individual findings are attached.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

EU implementation

Conclusions:

The study was conducted under GLP according to OECD guideline 402 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation. Hence, the results can be considered as reliable to assess the acute oral toxicity in rats.
Following single application of CAS 73912-21-7 at a dose of 2000 mg/kg bw, the animals did not show any general clinical signs. No pathological changes on the treated skin of males and females were found. All animals survived the experiment. During the 14-day experiment, body weight gain was found in all animals. Gross examination did not reveal any pathological changes in the examined animals. So it may be stated that the median lethal dose (LD50) of CAS 73912-21-7 is greater than 2000 mg/kg b.w. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, CAS 73912-21-7, does not need to be considered as irritating to rat skin.
According to the Regulation (EC) No. 1272/2008, it may be concluded that CAS 73912-21-7 is beyond categorization.

Executive summary:

In an acute dermal toxicity study (OECD 402), groups of 8-12 weeks old Wistar (RccHan:WIST) rats (5/sex) were dermally exposed to CAS 73912-21-7 in Arachis oil BP for 24 hours on 10% of body surface area at a dose of 2000 mg/kg bw under semi-occlusive coverage. Animals then were observed for 14 days.

 

Following single application of the test item, the animals did not show any general clinical signs. No pathological changes on the treated skin of males and females were found. All animals survived the experiment. During the 14-day experiment, body weight gain was found in all animals. Gross examination did not reveal any pathological changes in the examined animals. Hence, the following results could be gained:

 

LD0(dermal) ≥ 2000 mg/kg bw

LD50(dermal) > 2000 mg/kg bw

 

CAS 73912-21-7 is of low Toxicity based on the LD50 determined. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, CAS 73912-21-7 should not be considered as irritating to rat skin.

According to Regulation (EC) No. 1272/2008, it may be concluded that CAS 73912-21-7 is beyond categorization.