2-hydroxymethyl-9-methyl-6-(1-methylethyl)-1,4-dioxaspiro[4.5]decane

Acute Toxicity: dermal

Administrative data

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: Well documented study according to GLP and following OECD guideline.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2-hydroxymethyl-9-methyl-6-(1-methylethyl)-1,4-dioxaspiro[4.5]decane

EC Number:

408-200-3

EC Name:

2-hydroxymethyl-9-methyl-6-(1-methylethyl)-1,4-dioxaspiro[4.5]decane

Cas Number:

63187-91-7

Molecular formula:

C13H24O3

IUPAC Name:

[9-methyl-6-(propan-2-yl)-1,4-dioxaspiro[4.5]decan-2-yl]methanol

Test material form:

other: liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

HUSBANDRY
Room number: 12.
Conditions
Standard Laboratory Conditions. The room was air-conditioned with 15 air changes per hour and the environment controlled with optimal conditions
considered as being a temperature of 21°C and a relative humidity of 55%. Occasional fluctuations from these optimal conditions were noted, but were considered not to have adversely affected study integrity. Lighting was 12 hours artificial fluorescent light and 12 hours dark per day.

Accomodation
Individually housed in polycarbonate cages containing purified sawdust as bedding material (Woody SPF, supplied by Broekman Institute, Someren, The Netherlands). Certificates of analysis were examined and then retained in the RCC NOTOX archives.

Diet
Free access to standard pelleted laboratory animal diet (Kliba 343 from Klingentalmühle AG, Kaiseraugst, Switzerland). Certificates of analysis were examined and then retained in the RCC NOTOX archives.

Water
Free access to tap-water. Certificates of analysis (performed quarterly) were examined and then retained in the RCC NOTOX archives.

Administration / exposure

Vehicle:

petrolatum

Details on dermal exposure:

The formulation was applied to an area of approximately 25 cm 2( 5x5 cm) for males and 18 cm 2( 3.5x5 cm) for females by application on a gauze patch fixed successively to aluminium foil and flexible bandage (Coban, 3M, St. Paul, U.S.A.), with drops of petrolatum.

Duration of exposure:

24 hours, whereafter residual test substance was removed with tissue moistened with tap-water.

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

OBSERVATIONS

Mortality / Viability
At periodic intervals on the day of dosing (day 1) and twice daily thereafter for 14 days.

Body Weights
Days 1 (pre-administration), 8 and 15.

Clinical signs
At periodic intervals on the day of dosing (day 1) and once daily thereafter for 14 days. All signs of reaction to treatment were recorded with
particular attention paid to changes in the skin (treated skin), fur, eyes and mucous membranes, as well as to behaviour pattern, tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.


PATHOLOGY
Necropsy
All animals surviving to the end of the observation period were sacrificed by
oxygen/carbon dioxide asphyxiation and subjected to necropsy. Descriptions of
all macroscopic abnormalities were recorded.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occurred during the study period.

Clinical signs:

other: No signs of ill health or behavioural changes were observed.

Gross pathology:

Macroscopic post mortern examination of the surviving animals at termination revealed no abnormalities that were considered to have arisen as an effect of treatment. A light-brown appearance of the processus papillaris in the liver, as noted in one male, was considered not to be treatment related.

Other findings:

In the majority of the animals, scales and erythema were observed an the treated skin area an days 4-7.

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The dermal LD50 value of the test substance in rats of either sex was established as exceeding 2000 mg/kg body weight.

According to the EEC criteria for classification and labelling requirements for dangerous substances (EEC Directive 83/467/EEC, Annex VI of the EEC
Directive 67/548/EEC), the test substance does not need to be classified and has no obligatory labelling requirement.

Executive summary:

The purpose of this study was to assess the toxicity of the test article when administered to rats as a single dermal dose. The study was carried out in accordance with OECD Guideline No. 402, "Acute Dermal Toxicity" and EEC Directive 84/449/EEC, Part B.3, "Acute Toxicity - Dermal". The test substance was administered by dermal application, to five rats of each sex, at 2000 mg/kg body weight. Macroscopic examination was performed at the end of the experimental period. No animals died during the study. No signs of ill health or behavioural changes were observed. The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain. In the majority of animals, scales and erythema were noted on the treated skin area on days 4-7. Macroscopic post mortem examination of the surviving animals at termination revealed no abnormalities that were considered to have arisen as an effect of treatment. The dermal LD50 value of the test substance in rats of either sex was established as exceeding 2000 mg/kg body weight. Based on these results results,the substance should not be classified as acute toxic according to the criteria described in EU Regulation No. 1272/2008 on the Classification, Labelling and Packaging of Substances and Mixtures (CLP).

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