Registration Dossier

Toxicological information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Recent, well documented study published in open literature

Data source

Reference
Reference Type:
publication
Title:
Severe Poisoning After Accidental Pediatric Ingestion of Glycol Ethers
Author:
Wang GS, Yin S, Shear B, Heard K
Year:
2012
Bibliographic source:
Pediatrics 130, p1026;

Materials and methods

Study type:
poisoning incident
Endpoint addressed:
acute toxicity: oral
Principles of method if other than guideline:
Case study
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Composition of brake fluid:
5%–50% polyethylene glycol monomethyl ether
15%–40% triethylene glycol monoethyl ether
1%–30% triethylene glycol monomethyl ether
1%–25% triethylene glycol monobutyl ether
1%–20% polyethylene glycol, monobutyl ether
1%–20% triethylene glycol
10% of other glycol ethers

Method

Type of population:
general
Subjects:
- Number of subjects exposed: 1
- Sex: Male
- Age:22 month old child
- Known diseases: Healthy
Ethical approval:
not applicable
Route of exposure:
oral
Reason of exposure:
accidental
Exposure assessment:
estimated
Details on exposure:
330mls of brake fluid consumed. Assuming a mass of 12kg, this is estimated as a dose of 27g/kg.
Examinations:
- Urine analysis: Yes
- Haematology/clinical chemistry: Yes
- Lung function parameters: No
Medical treatment:
patient was then intubated by using rocuronium, atropine, and etomidate. 15mg/kg Fomepizole administered and hemodialysis started 4.5hrs after ingestion. Dopamine infusion titrated to 10 mg/kg per minute to maintain normal blood pressures. 2 mEq/kg of sodium bicarbonate IV bolus.

Results and discussion

Clinical signs:
Somnolent but arousable. Heart rate 173 bpm, respiratory rate was 36 bpm, temperature 37.4°C, blood pressure was 96/38 mm Hg, and oxygen saturation of 90% to 93% on room air.
Results of examinations:
- Urine analysis: normal.
- Haematology/clinical chemistry: metabolic acidosis with an anion gap of 18. Normal haematology and serum transaminase levels.
- Other: CAT scan showed normal brain function.
Effectivity of medical treatment:
Neither progression nor improvement in clinical or metabolic status was noted after the fomepizole.
Outcome of incidence:
Patient discharged on day 3 fully recovered with no complications.

Any other information on results incl. tables

The authors noted that most pediatric ingestions of glycol ethers are accidental and small in amount, do not develop clinical sequelae, and that very few cases require treatment. This suggests a low order of acute toxicity to humans.

Applicant's summary and conclusion

Executive summary:

A young child (22 months old) accidentally consumed a very large dose of brake fluid, which is predominantly composed of triethylene glycol alkyl ethers (where the alkyl is either methyl, ethyl or butyl). The dose was estimated to be in excess of 20g/kg. Exposure triggered severe metabolic acidosis and other clinical symptoms briefly requiring intensive care, including haemodialysis, but the patient fully recovered within 3 days with no complications.