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Description of key information

Results from 2 reliable studies in rats administered the substance by the oral or dermal route indicate adverse effects by the oral route only. The acute oral LD50 is between 300 mg/kg (no mortality) and 2000 mg/kg (100% mortality).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-11-27 to 2010-02-12
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 7 weeks old
- Weight at study initiation: 164 to 174 grams
- Fasting period before study: Overnight prior to dosing (Day –1) up to 4 hours after dosing.
- Housing: Polycarbonate cages measuring 59x38.5x20 cm, with stainless steel mesh lid and floor.
- Diet (e.g. ad libitum): 4 RF 18, ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): Approximately 15 to 25 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours


IN-LIFE DATES: From: 22 October 2009 To: 2009-12-29
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 and 30 mg/ml
- Amount of vehicle (if gavage): Dose volume of 10 ml/kg of body weight for each animal.
- Justification for choice of vehicle: no justification given
- Lot/batch no. (if required):
- Purity: no data


MAXIMUM DOSE VOLUME APPLIED: Dose volume of 10 ml/kg of body weight for each animal.


DOSAGE PREPARATION (if unusual):


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: A first sub-group of 3 female animals was dosed at a level of 2000 mg/kg (Step 1). 2000 mg/kg bw was chosen as this is the upper threshold value for the classification of oral toxic properties of a test substance.
Doses:
2000 and 300 mg/kg bw
No. of animals per sex per dose:
3 animals for the high dose group (Step 1); 2 groups each consisting of 3 animals for testing 300 mg/kg bw (Step 2 and step 3, respectively).
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Mortality and morbidity : Twice daily. Clinical signs 0.5, 2 and 4 hours after dosing, daily thereafter (14 days)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
No statistics applied.
Key result
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Mortality occurred in all animals dosed at 2000 mg/kg body weight (Step 1); two animals were found dead approximately 5 hours after dosing and the remaining animal was found dead on Day 4.
No mortality was observed in the animals dosed at 300 mg/kg body weight (Steps 2 and 3).
Clinical signs:
other: 2000 mg/kg bw: Piloerection, prone posture, unconscious and lachrymation were observed in all animals on the day of dosing. Prior to death the surviving animal appeared moribund on Days 2 and 3. Clinical signs observed on the day of dosing in the first su
Gross pathology:
No abnormalities were observed at necropsy examination performed in early decedent animals dosed at 2000 mg/kg (Step 1) and in those treated at 300 mg/kg (Steps 2 and 3) at the end of the observation period.
Other findings:
none reported
Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The mortality pattern of DIOX alcohol demonstrates the LD50 to be greater than 300 mg/kg but less than 2000 mg/kg body weight. European Directives concerning the classification, packaging and labelling of dangerous substances and mixtures would indicate the classification "Acute oral toxicity - Category 4".
Executive summary:

The acute toxicity of DIOX alcohol was investigated following a single oral administration to the Sprague Dawley rat followed by a 14-day observation period. The study followed the protocol according to OECD Guideline 423.

A first sub-group of 3 female animals was initially dosed at 2000 mg/kg body weight (Step 1). Mortality occurred in all animals between Day 1 and 4 after dosing. Piloerection, prone posture, lachrymation, unconscious and moribund appearance were observed prior to death with a various incidence.

A second and third subgroup, each composed of 3 females, were then dosed at 300 mg/kg body weight (Steps 2 and 3). No mortality was recorded in any animal. Clinical signs related to treatment were limited to hunched posture and/or piloerection. Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were observed at necropsy examination performed on the animals treated at 2000 or 300 mg/kg.

The results indicate that the test item, DIOX alcohol, has a mortality pattern of a LD50 to be greater than 300 mg/kg but less than 2000 mg/kg body weight. European Directives concerning the classification, packaging and labelling of dangerous substances and mixtures would indicate the following:

Classification : Acute oral toxicity - Category 4

Signal word : Warning

Hazard statement (Oral) : H302 Harmful if swallowed

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
Reliable study

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2009-11-17 to 2010-02-15
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6 to 8 weeks old
- Weight at study initiation: 164 to 196 grams
- Fasting period before study: not reported
- Housing: Individually caged (both during acclimatisation and study). Polycarbonate cages measuring 42.5x26.6x18 cm with stainless steel mesh lid and floor.
- Diet (e.g. ad libitum): 4 RF 18 ( ad libitum)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 2°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): Approximately 15 to 25 air changes per hour
- Photoperiod (hrs dark / hrs light): Artificial (fluorescent tubes), daily light/dark cycle of 12/12 hours


IN-LIFE DATES: From: 2009-11-26 To: 2009-12-24
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: dorsal surfaces of the trunk
- % coverage: approximately 10% of body surface
- Type of wrap if used: A patch of surgical gauze covered by a strip of synthetic film was placed over the treated site and the whole assembly held in place by encircling the trunk of the animal with a length of elastic adhesive bandage, this forming a semi-occlusive barrier.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): After exposure, the adhesive bandage and gauze patch were removed. The treatment area was cleaned by gentle swabbing of the skin with cotton wool soaked with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw (328 - 388 mg per animal)
- Concentration (if solution): The liquid test item was used in the condition supplied.
- Constant volume or concentration used: yes


VEHICLE
no vehicle used
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality and morbidity: twice daily
Clinical signs : Day of dosing (on dosing, approximately 1, 2 and 4 hours after dosing). Daily thereafter (14 days).
Body weight : Allocation (Day-1), Days 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology
Statistics:
no statistics applied
Preliminary study:
not reported
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
no indication of skin irritation up to the relevant limit dose level
Mortality:
no mortalities
Clinical signs:
other: none observed
Gross pathology:
No abnormalities were found at necropsy in the animals at termination of the study.
Other findings:
none reported
Interpretation of results:
GHS criteria not met
Conclusions:
The results indicate that the test item, DIOX alcohol, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.
Executive summary:

The acute toxicity of DIOX alcohol was investigated following dermal administration of a single dose to the rat. The study followed the protocol according to OECD Guideline 402.

A single dose of 2000 mg/kg was administered to a group of 5 male and 5 female animals for 24 hours. After 14 days all animals were killed and subjected to necropsy examination. No mortality occurred and no signs of toxicity were observed in male or female animals during the observation period. The body weight changes observed during the study were within the expected range for this species and age of animals. No abnormalities were found at necropsy in the animals at termination of the study. No abnormalities were observed at the treated site.

These results indicate that the test item, DIOX alcohol, has no toxic effect on the rat following dermal exposure over a 24 hour period at a level of 2000 mg/kg. The lack of mortality demonstrates the LD50 to be greater than 2000 mg/kg.

European Directives concerning the classification, packaging and labelling of dangerous substances and mixtures would indicate the following:

Classification : Not required

Signal word : None indicated

Hazard statement : None indicated

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Reliable study

Additional information

Justification for classification or non-classification

Based on the results of the acute oral toxicity study in rats the substance requires classification in acute toxicity category 4, with Hazard phrase H302 according to criteria in the CLP Regulation (EC) No.1272/2008.

Based on the results of the acute dermal toxicity study in rats, no classification is applied for the dermal route.