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Description of key information

5 -ethyl-1,3 -dioxane-5 -methanol is of low acute oral toxicity: an acute oral LD50 > 2000 mg/kg bw is reported. A waiver is proposed for acute dermal toxicity in line with REACH guidance, as no classification can be predicted for this endpoint based on the findings of the acute oral toxicity study. A waiver is proposed in accordance with Column 2 of Annex VIII of the REACH Regulation for acute inhalation toxicity on the basis that acute toxicity data are available for the oral route, and that inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance.

5 -ethyl-1,3 -dioxane-5 -methanol is of low acute oral toxicity: an acute oral LD50 > 2000 mg/kg bw is reported. A waiver is proposed for acute dermal toxicity in line with REACH guidance, as no classification can be predicted for this endpoint based on the findings of the acute oral toxicity study. A waiver is proposed in accordance with Column 2 of Annex VIII of the REACH Regulation for acute inhalation toxicity on the basis that acute toxicity data are available for the oral route, and that inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance.

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:
guideline study
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Principles of method if other than guideline:
Not applicable.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Batch 9201; clear / colourless liquid
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
Source: Møllegaard Breeding Centre ApS, Ejby, DK-4623 Lille, Skensved
Age at study initiation: 6 - 7 weeks old
Weight at study initiation: 146 -163 g
Fasting period before study: Rats were fasted for approximately 18 hours prior to dosing
Housing: Housed in Macrolone type III cages (42 x 26 x 15cm), with 2 or 3 to a cage. Males and females were kept separated
Diet (e.g. ad libitum): Complete rodent diet "Altromin 1314" ad libitum
Water (e.g. ad libitum): Drinking water acidified with hydrochloric acid to pH 2.5 ad libitum
Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
Temperature (°C): 21 ± 3°C
Humidity (%): 55 ± 15%
Air changes (per hr): 10 times per hour
Photoperiod (hrs dark / hrs light): 12 hour photoperiod

IN-LIFE DATES: No information provided.
Route of administration:
oral: gavage
Vehicle:
other: Distilled water.
Details on oral exposure:
VEHICLE- Concentration in vehicle: 2000 mg/kg body weight. - Amount of vehicle (if gavage): No information provided. - Justification for choice of vehicle: No information provided. - Lot/batch no. (if required): No information provided. - Purity: No information provided. MAXIMUM DOSE VOLUME APPLIED: 10ml/kg body weight.DOSAGE PREPARATION (if unusual): No information provided. CLASS METHOD (if applicable)- Rationale for the selection of the starting dose: No information provided.
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 animals per sex per dose
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days - Frequency of observations and weighing: Bodyweights were recorded on Day 0, Day 7 and Day 14. Observations on clinical signs of toxicity were made 1, 2, 3 and 6 hours and daily thereafter from Day 1 to 14.- Necropsy of survivors performed: Any rats found dead during the 14 day observation period were subjected to a autopsy examination. All surviving rats were subjected to gross necropsy examination at the end of the 14 day osbervation period.- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: No information provided.
Statistics:
Not required
Preliminary study:
A dose-range finding study was conducted at a dose level of 2000 mg/kg bw
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One female rat died during the treatment.
Clinical signs:
At the 1 hour observation, 8 rats were comatose, 1 rat showed sedation, pinched abdomen and laboured respiration and 1 rat showed ataxia and pinched abdomen. At the 3 hour observation, 2 rats were still comatose, 2 rats showed ataxia and piloerection and the remaining 6 rats showed sedation, pinched abdomen, piloerection and paresis. At the 6 hour observation, 1 rat was found dead, 1 rat showed salivation and in all 9 surviving rats, sedation, pinched abdomen and piloerection were observed. On day 1, all rats showed sedation and pinched abdomen. From day 2 and throughout the rest of the 14 day observation period, all rats showed normal behaviour and appearance.
Body weight:
All surviving rats had normal body weight gain during the study period.
Gross pathology:
Autopsy of the rat that died from the treatment revealed no pathological findings that could be attributed to the treatment. No gross pathological findings related to the treatment wee observed following autopsy of the surviving rats.
Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the conditions of this study, the oral LD50 of CTF was >2000 mg/kg bw.
Executive summary:

The acute oral toxicity of CTF in rats was determined according to the method recommended in OECD Guideline 401. CTF was administered orally by gavage to 5 male and 5 female Wistar rats at a concentration of 2000 mg/kg bw. The test animals were observed for a period of 14 days following exposure and observations were made at regular intervals, including observations on body weight, clinical signs and any clinical signs of toxicity. All test animals were subjected to a gross necropsy at termination on day 14. With only one female rat found dead during the course of the exposure, the oral LD50 was above 2000 mg CTF/kg body weight under the conditions of this study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
A high quality modern GLP- and guideline-compliant study is available for this endpoint.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute oral toxicity

The acute oral toxicity of 5 -ethyl-1,3 -dioxane-5 -methanol (CTF) in rats was determined according to OECD Test Guideline 401 (Dyring Jacobsen, 1992). CTF was administered orally by gavage to 5 male and 5 female Wistar rats at a concentration of 2000 mg/kg bw. Animals were observed for a period of 14 days following exposure and observations were made at regular intervals, including observations of body weight, clinical signs and any signs of toxicity. Only one female rat was found dead during the course of the exposure: no pathological findings attributable to treatment were observed. All test animals were subjected to a gross necropsy at termination on Day 14. No gross pathological findings were observed in treated animals. The oral LD50 was determined to be >2000 mg/kg bw under the conditions of this study.

 

Acute dermal toxicity 

No study is available. A waiver is proposed for this endpoint based on REACH guidance, based on the low acute oral toxicity. CTF is not classified for acute oral toxicity (LD50 >2000 mg/kg bw); it can also be assumed that classification for acute dermal toxicity is not required. Specific testing for acute dermal toxicity is therefore not required.

 

Acute inhalation toxicity 

A waiver is proposed for acute inhalation studies in accordance with Column 2 of Annex VIII of the REACH Regulation on the basis that acute toxicity data are available for the oral route. Inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance. The substance is a non-volatile liquid and the use pattern indicates that significant inhalation exposure is unlikely.

Justification for classification or non-classification

The oral LD50 of 5 -ethyl-1,3 -dioxane-5 -methanol in rats is > 2000 mg/kg bw. CTF is classified for acute oral toxicity in Category 5 according to GHS; classification for acute oral toxicity is not required under the CLP Regulation.