2-(4-methylcyclohex-3-en-1-yl)propan-2-ol

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1975

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Study well documented, meets generally accepted scientific principles, acceptable for assessment

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

publication

Title:

An Investigation of Recurrent Pine Oil Poisoning in an Infant by the Use of Gas Chromatographic-Mass Spectrometric Methods.

Author:

Hill RM, Barer J, Hill LL, Butler CM, Harvey DJ and Horning MG.

Year:

1975

Bibliographic source:

J Pediatr. 87(1):115-8.

Materials and methods

Study type:

poisoning incident

Endpoint addressed:

other: terpineol poisoning

Principles of method if other than guideline:

An 18-month-old infant admitted to six times in a period of six months for episodes consisting of coughing, respiratory depression, hematemesis, coma, dehydration and lesions about the mouth. A negative history of ingestion of toxins was repeatedly obtained from the family and two home inspections by the local Health Department failed to identify potential toxins. Urine sample from the infant was analysed using GC-MS analysis method.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

p-menth-1-en-8-ol

EC Number:

233-986-8

EC Name:

p-menth-1-en-8-ol

Cas Number:

10482-56-1

Molecular formula:

C10H18O

IUPAC Name:

α,α-4-trimethyl-(1S)-3-cyclohexene-1-methanol

Constituent 2

Reference substance name:

(R)-α,α,4-trimethylcyclohex-3-ene-1-methanol

EC Number:

232-081-5

EC Name:

(R)-α,α,4-trimethylcyclohex-3-ene-1-methanol

Cas Number:

7785-53-7

Molecular formula:

C10H18O

IUPAC Name:

α,α-4-trimethyl-(1R)-3-cyclohexene-1-methanol

Constituent 3

Reference substance name:

1-methyl-4-(1-methylethylidene)cyclohexan-1-ol

EC Number:

209-584-3

EC Name:

1-methyl-4-(1-methylethylidene)cyclohexan-1-ol

Cas Number:

586-81-2

Molecular formula:

C10H18O

IUPAC Name:

1-methyl-4-(1-methylethylidene)-cyclohexanol

Test material form:

liquid

Method

Type of population:

general

Subjects:

- Number of subjects exposed: One infant
- Sex: Male
- Age: 18 months

Ethical approval:

not applicable

Route of exposure:

other: poisoning

Reason of exposure:

other: accidental or intentional

Exposure assessment:

estimated

Details on exposure:

Infant admitted to six times in a period of six months for episodes consisting of coughing, respiratory depression, hematemesis, coma, dehydration and lesions about the mouth. A negative history of ingestion of toxins was repeatedly obtained from the family and two home inspections by the local Health Department failed to identify potential toxins. Metabolic work-up was entirely negative.

Examinations:

- Urine analysis: Random urine samples were collected from the infant on the fifth admission to Hospital during various stages of his recovery, i.e., while comatose, lethargic, and alert. During the sixth admission, additional samples of urine were obtained from the patient, and samples were also collected from the mother, father and sibling. Samples were kept frozen (-14 °C) until analyzed.

Medical treatment:

None

Results and discussion

Clinical signs:

Mild respiratory depression, fever (100-104 °F), dehydration, coughing, hematemesis, listlessness, coma, erythema of the oral pharynx, and lesions of the lips and tonsillar pillars

Results of examinations:

- Urine analysis: Utilizing methods of GC-MS, metabolites of α-terpineol were isolated from infant urine. Gas chromatographic analyses of the neutral fraction isolated from the infant's urine revealed the major metabolite i.e., p-methan-1, 2, 8-triol ((HO)2-α-terpineol)) and Mass spectral analyses indicated that the major metabolite was a triol.
These metabolites were confirmed by mass spectrometry to be the same metabolites excreted by Sprague-Dawley rats injected with α-terpineol or pine oil.

Effectivity of medical treatment:

No medical treatment done.

Outcome of incidence:

The child had no additional episodes after physical separation from the home environment.

Any other information on results incl. tables

None

Applicant's summary and conclusion

Conclusions:

Results of GC-MS analysis suggested that the infant had ingested preparation containing pine oil, which causes the clinical symptoms in the child. The child had no additional episodes after physical separation from the home environment.

Executive summary:

An 18-month-old infant admitted to six times in a period of six months for episodes consisting of coughing, respiratory depression, hematemesis, coma, dehydration and lesions about the mouth. A negative history of ingestion of toxins was repeatedly obtained from the family and two home inspections by the local Health Department failed to identify potential toxins. Random urine samples were collected from the infant and also from the family members and samples were analysed by gas chromatographic-mass spectrometric (GC-MS) method.

 

GC-MS analysis revealed the metabolites of alpha-terpineol from infant urine. Gas chromatographic analyses of the neutral fraction isolated from the infant's urine revealed the major metabolite i.e., p-methan-1, 2, 8-triol ((HO)2 -alpha-terpineol)) and mass spectral analyses indicated that the major metabolite was a triol. These metabolites were confirmed by mass spectrometry to be the same metabolites excreted by Sprague-Dawley rats injected with alpha-terpineol or pine oil. The results of these analyses demonstrate that the child had ingested some preparation containing pine oil and that this was the toxin causing the clinical symptoms observed in the child. The child had no additional episodes after physical separation from the home environment.