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Description of key information

In regulatory guideline acute toxicity studies, there were no mortalities among 3 male and 3 female animals dosed with a single oral dose of 2000 mg/kg and there were no mortalities among 5 males and 5 females dosed dermally at 2000 mg/kg .

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with guideline OECD423 and EU B.1 and to GLP.
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
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Test animal: Sprague-Dawley CD (Cr1: CD® ( SD) IGS BR Strain)
- Source: Charles River (UK) Ltd, Margate, Kent, UK
- Age at study initiation: Approximately eight weeks old
- Weight at study initiation: 182 to 282g. All females were below guideline value of 200g but this is not considered to have affected the outcome of the study
- Fasting period before study: Overnight before study
- Housing: The animals were housed in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes
- Diet (e.g. ad libitum): Free access food (Rat and Mouse Expanded Diet No.1, Special Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): Free access to mains drinking water a
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C a
- Humidity (%): 30 to 70%
- Air changes (per hr): The rate of air exchange was at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): Lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness
Route of administration:
oral: gavage
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200mg/mL
- Amount of vehicle (if gavage): 10mL/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: not reported - the highest of the 4 dosage levels on the OECD/EU test guideline was used.

Doses:
2000 mg/kg
No. of animals per sex per dose:
Three males and three females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: 30minutes, 1 hour, 2 hours and 4 hours post dosing and then daily
- Necropsy of survivors performed: Yes
- Other examinations performed: Clinical signs daily, body weight prior to dosing and on days 7 and 14 pot dosing, gross pathology on necropsy:
Statistics:
Not reported
Preliminary study:
Not reported
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Remarks on result:
other: The LD50 of 2500 is based on the flow chart from the acute toxic class method for no mortality in either of the sexes tested.
Mortality:
There were no deaths.
Clinical signs:
Signs of systemic toxicity noted in all males during the day of dosing were hunched posture and lethargy. All males appeared normal one day after dosing. There were no signs of systemic toxicity noted in females.
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: other: EU CLP
Conclusions:
The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Cr1: CD® ( SD) IGS BR) strain rat was estimated from the flow chart Annex 3d of OECD Test guideline 423 as being greater than 2500 mg/kg bodyweight.

The test material does not meet the criteria for classification according to EU CLP labelling regulations for acute toxicity..
Executive summary:

The study was performed to assess the acute oral toxicity of the test material following a single oral administration in the Sprague-Dawley CD (Cr1: CD® ( SD) 1GS BR) strain rat. The method was designed to meet the requirements of the following: a) OECD Guidelines for the Testing of Chemicals No. 423 "Acute Oral Toxicity — Acute Toxic Class Method" (adopted 22 March 1996) and b) Commission Directive 96/54/EC Method B1 tris Acute Toxicity (Oral) — Acute Toxic Class Method Method. A group of three fasted females was treated with the test material at a dose level of 2000 mg/kg bodyweight. This was followed by a group of three fasted animals of the other sex at the same dose level. The test material was administered orally as a suspension in arachis oil BP. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths.

Signs of systemic toxicity noted in all males during the day of dosing were hunched posture and lethargy. There were no signs of systemic toxicity noted in females. All animals showed expected gains in bodyweight over the study period and no abnormalities were noted at necropsy.

The acute oral median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Crl: CD® (SD) 1GS BR) strain rat was estimated from the flow chart Annex 3d of OECD test guideline 423 as being greater than 2500 mg/kg bodyweight.

The test material does not meet the criteria for classification for acute toxicity according to EU CLP labelling regulations.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 500 mg/kg bw
Quality of whole database:
Reliability Level 1 (reliable without restrictions)

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Test conducted according to published OECD guideline 402 and to GLP.
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
GLP compliance:
yes (incl. QA statement)
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
- Test animal: Sprague-Dawley CD (Cr1: CD® ( SD) 1GS BR) strain
- Source: Charles River (UK) Ltd, Margate, Kent, UK.
- Age at study initiation: Approximately 8 weeks
- Weight at study initiation: At least 200g
- Housing: In suspended 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): Free access to food (Rat and Mouse SQC Expanded Diet No. 1, Special Diets Services Limited, Witham, Essex, UK)
- Water (e.g. ad libitum): Free access to mains drinking water

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 25°C
- Humidity (%): 30 to 70%
- Air changes (per hr): At least 15 per hour
- Photoperiod (hrs dark / hrs light): Controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness
Type of coverage:
semiocclusive
Vehicle:
other: solid moistened with distilled water
Details on dermal exposure:
TEST SITE
- Area of exposure: Area on back and flanks clipped free of hair
- % coverage: Approximating to 10% of the total body surface area
- Type of wrap if used: 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 bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test material
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- For solids, paste formed: yes - moistened with distilled water

Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 of each sex
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 1/2, 1, 2 and 4 hours alter dosing and subsequently once daily for fourteen days.
- Necropsy of survivors performed: yes
- Other examinations performed: Skin reactions according to Draize criteria - see below -Any other skin reactions, if present were also recorded.

EVALUATION OF SKIN REACTIONS

Erythema and Eschar Formation Value:
No erythema (0)
Very slight erythema (barely perceptible) (1)
Well-defined erythema (2)
Moderate to severe erythema (3)
Severe erythema (beet redness) to slight eschar formation (injuries in depth) (4)

Oedema Formation Value:
No oedema (0)
Very slight oedema (barely perceptible) (1)
Slight oedema (edges of area well-defined by definite raising) (2)
Moderate oedema (raised approximately 1 millimetre) (3)
Severe oedema (raised more than 1 millimetre and extending beyond the area of exposure) (4)

Individual bodyweights were recorded prior to application of the test material on Day 0 and on Days 7 and 14.



Statistics:
Not reported
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities
Mortality:
There were no deaths.
Clinical signs:
There were no signs of systernic toxicity
Body weight:
All animals showed expected gains in bodyweight over the study period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Skin reactions

Very slight erythema was noted at the treatment site of one male one day after dosing. No other signs of dermal irritation were noted in males.

Very slight to well-defined erythema was noted at the treatment sites all females one day after dosing with very slight erythema noted at the treatment sites of three females two days after dosing. Other skin reactions noted at the treatment sites of females were a hardened light brown coloured scab, small, superficial scattered scabs, crust formation and desquamation.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: other: EU CLP
Conclusions:
The acute dermal median lethal dose (LD50) of the test material, in the Sprague-Dawley CD (Cr1: CD® (SD) 1GS BR) strain rat was found to be greater than 2000 mg/kg bodyweight.
The test material does not meet the criteria for classification and will not require labelling for dermal toxicity in accordance with EU CLP labelling regulations.
Executive summary:

The study was performed to assess the acute dermal toxicity of the test material in the Sprague-Dawley CD (Crl: CD® (SD) 1GS BR) strain rat. The method was designed to meet the requirements of the following: a) OECD Guidelines for the Testing of Chemicals No. 402 "Acute Dermal Toxicity" (adopted 24 February 1987) and b) Commission Directive 92/69/EEC Method B3 Acute Taxicity (Dermal).

A group of ten animals (five males and five females) was given a single, 24-hour, semi-occluded dermal application of test material to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and bodyweight development were monitored during the study. All animals were subjected to gross necropsy.

There were no deaths. There were no signs of systemic toxicity.

In relation to the skin, very slight to well-defined erythema was noted at the treatment sites of one male and all females. Other signs of skin irritation noted at the treatment sites of females were a hardened light brown coloured scab, small superficial scattered scabs, crust Formation and desquamation.

All animals showed expected gains in bodyweight over the study period. No abnormalities were noted at necropsy.

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD (Cr1: CD® (SD) IGS BR) strain rat was found to be greater than 2000 mg/kg bodyweight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Reliability Level 1 (reliable without restrictions)

Additional information

As required under Annex VII of REACH the acute oral toxicity of decan-1,2 -diol was evaluated; the acute toxic class method was used. No mortalities arose following administration of a single oral dose of 2000 mg/kg by gavage. The rat oral LD50 was, therefore, calculated to be >2500 mg/kg.

 

In addition, the dermal acute toxicity study also showed no mortality in 5 male and 5 female rats dosed at 2000 mg/kg. The rat dermal LD50 was, therefore, calculated to be >2000 mg/kg.


Justification for selection of acute toxicity – oral endpoint
Study conducted in accordance with published guidelines OECD423 and EU B.1 and to GLP

Justification for selection of acute toxicity – dermal endpoint
Study conducted in accordance with published guidelines OECD402 and EU B.3 and to GLP

Justification for classification or non-classification

The test material does not meet the criteria for classification for acute oral or dermal toxicity according to EU CLP labelling regulations. The limit for classification is 2000 mg/kg and the LD50 for the test material exceeded that value in both oral and dermal studies.