1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Study conducted between April 1988 and June 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1988

Report date:

1988

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

GLP compliance:

yes

Test type:

other: modified procedure described by Noakes and Sanderson (similar to standard acute method)

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

EC Number:

402-950-5

EC Name:

1-(2,6-bis(4-tolyl)-1,3-dioxano(5,4-d)-1,3-dioxan-4-yl)ethane-1,2-diol

Cas Number:

87826-41-3

Molecular formula:

C22 H26 O6

IUPAC Name:

(1R)-1-[(4R,4aR,8aS)-2,6-bis(4-methylphenyl)-hexahydro-[1,3]dioxino[5,4-d][1,3]dioxin-4-yl]ethane-1,2-diol

Details on test material:

Test material:
Test material appearance: White powder
batch number: 4140626
Purity: 95% minimum

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River UK, Ltd, Manston Road, Margate, Kent
- Age at study initiation: Males were between 48 to 50 days old and females were between 56 to 65 days old
- Weight at study initiation: 278 g to 342 g for Males and 211 g to 267 g for Females
- Fasting period before study: not stated in report
- Housing: Rats were housed in pairs by sex and in steel mesh cages
- Diet (e.g. ad libitum): Free acess to Modified Expanded S.Q.C Rat and Mouse Diet No. 1
- Water (e.g. ad libitum): tap water
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):18 to 22 deg C
- Humidity (%): 44 to 54%
- Air changes (per hr): not stated in report
- Photoperiod (hrs dark / hrs light): 12 hours light followed by 12 hours of darkness

IN-LIFE DATES: From: Day of dosing (day 1) To: Day of sacrifice (day 14)

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: moistened with 0.5% sodium carboxymethyl in distilled water.

Details on dermal exposure:

TEST SITE
- Area of exposure: 6 cm by 10 cm
- Type of wrap if used: aluminium foil (held in place by an encircling band of waterproof plaster).

REMOVAL OF TEST SUBSTANCE
- Washing (if done): treated skin was washed with soap and water to remove residual test material and then rinsed with water and dried.
- Time after start of exposure: 24 hours

TEST MATERIAL
- For solids, paste formed: yes, test material was moistened with 0.5% w/v solution sodium carboxymethylcellulose in distilled water and applied to the shaved area at a dose level of 2100 mg/kg.

Duration of exposure:

24 hours

Doses:

0 (control) and 2100 mg/kg

No. of animals per sex per dose:

5 males and 5 females were tested at both the 0 and 2100 mg/kg dose range (e.g. 20 animals in total)

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: Animals were observed for clinical signs and behaviour frequently on the day of treatment, at least once each morning and afternoon on working days thereafter and at leaast once each other day. Bodyweights were recorded immediately prior to treatment on Day 1, on Day 8 and immediately prior to termination on Day 15.

- Necropsy of survivors performed: yes - all animals were killed by CO2 asphyxiation on Day 15 and subjected to gross post-mortem examination for external abnormalities and for abnormalities of the thoracic and abdominal viscera.
- Other examinations performed: skin irritation - after removal of the plaster, skin treatment sites were examined daily for evidence of skin irritation.

Statistics:

The significance of difference between bodyweight change of control and test groups was estimated by the two sample test of Dunnett.

Results and discussion

Preliminary study:

Range finding with 1 male and 1 female: no evidence of toxicity or skin irritation

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 100 mg/kg bw

Based on:

test mat.

Mortality:

There were no deaths during the study.

Clinical signs:

other: There were no treatment related clinical signs during the study.

Gross pathology:

There were no abnormal findings

Other findings:

Skin irritation: There was no evidence of skin irritation.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In both sexes, the acute dermal LD50 was greater than 2100 mg/kg bw.

Executive summary:

The purpose of the study is to determine the acute dermal toxicity of techncial GEL-ALL-MD to the rat.

Groups of 5 male and 5 female Sprague-Dawley rats received a single, 24 hour occluded, topical application of 2100 mg Technical Gel-ALL-MD/kg bodyweight, moistened with 0.5% w/v sodium carboxymethylcellulose in distilled water. A further 5 male and 5 female control animals were treated similarly except that no test material was applied to the skin. Animals were observed for 14 days after treatment and then examined post mortem.

There were no mortalities, no treatment-related clinical signs and no evidence of skin irritation. No treatment-related effects on bodyweight were recorded and no abnormalities were seen post-mortem.

In both sexes the acute dermal LD50 was greater than 2100 mg/kg bw.