Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

epidemiological data
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
3 (not reliable)
Rationale for reliability incl. deficiencies:
unsuitable test system
see strength and weaknesses for a detailed justification

Data source

Reference Type:
Air Toxics in Relation to Autism Diagnosis, Phenotype, and Severity ina U.S. Family-Based Study
Amy E.Kalkbrenner, Gayle C.Windham, Cheng Zheng, Rob McConnell, Nora L.Lee, James J.Schauer, Brian Thayer, Juhi Pandey, and Heather E.Volk
Bibliographic source:
Environmental Health Perspectives, (MAR 2018) Vol. 126, No. 3, pp. Article No.: 037004. CODEN: EVHPAZ. ISSN: 0091-6765. E-ISSN: 1552-9924

Materials and methods

Study type:
case control study (retrospective)
Endpoint addressed:
developmental toxicity / teratogenicity
Test guideline
no guideline followed
Principles of method if other than guideline:
The Authors included participants of a study [the Autism Genetic Resource Exchange (AGRE) ]who were born between 1994 and 2007 and had address information. They assessed associations between average annual concentrations at birth for each of 155 airtoxics from the U.S. EPA emissions-based National-scale Air Toxics Assessment and a) ASD diagnosis (1,540 cases and 477 controls); b) a continuous measure of autism-related traits, the Social Responsiveness Scale (SRS, among 1,272 cases and controls); and c) a measure of autism severity, the Calibrated Severity Score (among 1,380 cases).
In addition to the individual’s airtoxic level, mixed models (clustering on family) included the family mean air toxic level, birth year, and census covariates, with consideration of the false discovery rate.

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:


Type of population:
Ethical approval:
not specified
Exposure assessment:

Results and discussion

ASD diagnosis was positively associated with propionaldehyde (OR: 1.92, CI: 1.33-2.77).
Strengths and weaknesses:
Amongst approximately 150 substances assessed, propionaldehyd was positively associated with autism together with four other compounds, whereas 4 compounds were inversely associated with autism. Therefore, the association is most probably coincidential or rather weak due to the high number of chemicals assessed. Also, the air concentrations of the compounds assessed were only estimates based on 3 year interval means related to the adress of the families during pregnancy. The actual time spent at home was not taken into account. Also, there is a difference between outdoor and indoor volatile organic compound concentrations. Here only so called "Air toxics concentration" without further specification were estimated. Moreover, it is not possible to reflect synergistic or antagonistic effects of the huge number of pollutants present in the outdoor air in a study like this. Propionaldehyde was not the only compound the study population was exposed to.
Hence, the study was considered to be unreliable (Klimisch score 3).

Applicant's summary and conclusion