Exo-1-methyl-4-(1-methylethyl)-7-oxabicyclo[2.2.1]heptan-2-ol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1986-02-07 to 1986-03-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(1S,2S)-1-methyl-4-(propan-2-yl)-7-oxabicyclo[2.2.1]heptan-2-ol

Cas Number:

87172-89-2

IUPAC Name:

(1S,2S)-1-methyl-4-(propan-2-yl)-7-oxabicyclo[2.2.1]heptan-2-ol

Test material form:

solid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Young adult male and female Sprague-Dawley rats were obtained from Charles River Breeding Laboratories, Inc., Wilmington, MA.
- Age at study initiation: Young adult
- Weight at study initiation: males: 195.8 to 221.8 g; females: 204.0 to 224.6 g
- Fasting period before study: Yes. Animals were fased overnight (approximately 18 hours) prior the test.
- Housing: Animals were individually housed in wire mesh bottom cages.
- Diet: NIH open formula 07, certified feed (Zeigler Brothers, Inc., Gardners, PA); ad libitum
- Water: Fresh tap water; ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Doses:

900, 1046, 1216, 1643, 2220 and 3000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were weighted on the day of dosing (day 1) and on day 8 and 15 of the study. All animals will be observed for mortlity and toxic signs frequently during the day of dosing and twice daily (at least 5 hours apart) thereafter for a toal of 14 days.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, cage side observations will include changes in the fur and skin; eyes and mucous membranes; respiratory, circulatory, autonomic and central nervous systems; somatomotor activity and behavior pattern, observation of tremors, convulsions, salivation, diarrhea, lethargy, and coma.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 429 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 169 - <= 1 689

Effect levels 2

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

1 053 mg/kg bw

Based on:

test mat.

95% CL:

>= 952 - <= 1 154

Effect levels 3

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 293 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 123 - <= 1 464

Mortality:

All male rats died in the two highest dose groups of 2220 and 3000 mg/kg. All female animals died in the four highest dose groups. For details see table 1 in the section 'Any other information on results incl. tables'.

Clinical signs:

See table 1 in the section 'Any other information on results

Gross pathology:

See table 2 in the section 'Any other information on results

Any other information on results incl. tables

Table 1: Incidence of daily observations

Dose Level mg/kg	Observations	No. Affected/No. Examined
		Males	Females
900	Ataxia	5/5	5/5
	Decreased activity	4/5	5/5
	Salivation	1/5	3/5
	Lacrimation	0/5	4/5
	Appears to have blood in urine	0/5	1/5
	Wet abdomen	0/5	3/5
1046	Ataxia	4/5	5/5
	Decreased activity	2/5	5/5
	Salivation	2/5	1/5
	Lacrimation	1/5	4/5
	Appears to have blood in urine	0/5	1/5
	Wet abdomen	0/5	4/5
	Hair loss-abdomen	0/5	1/5
	Death	1/5	2/5
1216	Ataxia	4/5	4/5
	Decreased activity	3/5	5/5
	Salivation	2/5	3/5
	Appears to have blood in urine	1/5	0/5
	Lacrimation	1/5	4/5
	Wet abdomen	1/5	0/5
	Death	1/5	5/5
1643	Ataxia	4/5	1/5
	Decreased activity	4/5	5/5
	Salivation	1/5	3/5
	Wet abdomen	1/5	0/5
	Lacrimation	1/5	3/5
	Death	3/5	5/5
2220	Salivation	4/5	3/5
	Decreased activity	5/5	5/5
	Ataxia	1/5	2/5
	Lacrimation	0/5	3/5
	Death	5/5	5/5
3000	Decreased activity	5/5	5/5
	Ataxia	2/5	3/5
	Salivation	2/5	2/5
	Lacrimation	0/5	1/5
	Death	5/5	5/5

Table 2: Incidence of Necropsy Findings

Dosage Level mg/kg	Findings	No. Affected/No. Examined
		Males	Females
900	No noteworthy findings	2/5	5/5
	Lungs: multiple dark spots	3/5	0/5
1046	No noteworthy findings	4/5	3/5
	Thoracic cavity: contains bloodlike liquid	1/5	0/5
	Lungs: dark and/or red areas	1/5	1/5
	Liver: pale	0/5	1/5
	Bladder: contains bloodlike liquid	0/5	1/5
1216	External appearance: corneal opacity (left eye)	0/5	2/5
	No noteworthy findings	4/5	0/5
	Lungs: puffy (dark)	1/5	2/5
	Thymus: red spots	1/5	3/5
	Liver: dark	1/5	4/5
	Stomach (pyloric region): small red nodule	1/5	1/5
	Stomach (pyloric region): red	0/5	1/5
1643	External appearance: corneal opacity (right eye)	1/5	0/5
	No noteworthy findings	2/5	1/5
	Thymus: red spot	1/5	0/5
	Lungs: puffy	3/5	0/5
	Lungs: dark red areas	0/5	1/5
	Lungs: pale	1/5	0/5
	Liver: dark	3/5	3/5
	Stomach (pyloric region): rad nodule	1/5	0/5
	Stomach (pyloric region): red	1/5	0/5
2220	External appearance: corneal opacity (left eye)	0/5	1/5
	Liver: dark	4/5	5/5
	Lungs: puffy	1/5	2/5
	Lungs: pale	1/5	0/5
	Lungs: dark spots	1/5	0/5
	Thymus: red spots	0/5	2/5
	Stomach (pyloric region): red areas	0/5	1/5
3000	External appearance: corneal opacity (left eye)	0/5	1/5
	Lungs: puffy (pale)	4/5	4/5
	Liver: dark	5/5	5/5
	Thymus: red spots	0/5	1/5
	Stomach 8pyloric region). Red areas	0/5	1/5