Bis(2-ethylhexyl) phthalate

Direct observations: clinical cases, poisoning incidents and other

Administrative data

Endpoint:

direct observations: clinical cases, poisoning incidents and other

Type of information:

other: Review

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data from a review

Data source

Reference

Reference 1

Reference Type:

review article or handbook

Title:

European Union Risk Assessment Report BIS(2-ETHYLHEXYL) PHTHALATE (DEHP) CAS No: 117-81-7 EINECS No: 204-211-0 RISK ASSESSMENT

Author:

ECB

Year:

2008

Reference 2

Reference Type:

publication

Title:

Di(2-ethylhexyl) phthalate as plasticizer in PVC respiratory tubing systems: indications of hazardous effects on pulmonary function in mechanically ventilated, preterm infants.

Author:

Roth B, Herkenrath P, Lehmann H-J, et al.

Year:

1988

Bibliographic source:

Eur. J. Pediatr. 147, 41-46.

Reference 3

Reference Type:

publication

Title:

Verhdl. Dt. Ges. Arbeitsmed.

Author:

Thiess AM, Frentzel-Beyme R and Wieland R

Year:

1978

Bibliographic source:

Gentner Verlag, Stuttgart, 155-164.

Reference 4

Reference Type:

publication

Title:

Unnamed

Year:

1978

Reference 5

Reference Type:

publication

Title:

Health status of workers exposed to phthalate plasticizers in the manufacture of artificial leather and films based on PVC resins.

Author:

Milkov LE, Aldyreva MV, Popova TB, et al.

Year:

1973

Bibliographic source:

Environ. Health Perspect. 3, 175-178.

Reference 6

Reference Type:

publication

Title:

Horizontal and longitudinal study of a population employed in the production of phthalates.

Author:

Gilioli R, Bulgheroni C, Terrana T, et al.

Year:

1978

Bibliographic source:

Med. Lav. 69, 620-631.

Reference 7

Reference Type:

publication

Title:

Phthalate ester Exposure- air Levels and Health of Workers Precessing Polyvinylchloride.

Author:

Nielsen J, Åkesson B and Skerfving S

Year:

1985

Bibliographic source:

Am. ind. Hyg. Assoc. J. 46(11), 643-647.

Materials and methods

Study type:

other:

Endpoint addressed:

repeated dose toxicity: oral

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2-ethylhexyl) phthalate

EC Number:

204-211-0

EC Name:

Bis(2-ethylhexyl) phthalate

Cas Number:

117-81-7

Molecular formula:

C24H38O4

IUPAC Name:

1,2-bis(2-ethylhexyl) benzene-1,2-dicarboxylate

Method

Type of population:

occupational

Applicant's summary and conclusion

Executive summary:

A case report suggests that inhalation of DEHP may induce toxic damage of the lungs in the preterm infant. In preterm infants, artificially ventilated with PVC respiratory tubes, unusual lung disorders resembling those observed in hyaline membrane disease were observed during the fourth week of life in two infants (Roth et al., 1988). In a third infant, who died two weeks after birth, DEHP was detected in the lung tissue but not in the liver tissue. The estimated inhalative exposure in the three infants ranged between 1µg/hour – 4,200µhour. DEHP, but not MEHP, could be demonstrated in urine samples. The authors assumed that these findings were causally related to the exposure to high doses of DEHP released from the PVC tubes.

A morbidity study was carried out on a group of 97 men and 4 women employed in a German plant producing DEHP (Thiess et al., 1978b). The average exposure period was 12 years (4 months to 35 years). Background levels were generally low (0.001-0.004 ppm≈0.016-0.064 mg/m3) with higher levels up to 0.01 ppm (0.16 mg/m3) in the vicinity of the chemical reactor. Blood lipids, serum activities of liver enzymes, and routine haematological tests were normal, and no excess of any pathological condition was found. All 58 children fathered by the exposed men were normal. Due to the low exposure levels and the lack of a referent group, this study is considered inadequate with respect to the risk assessment.

A mortality study of 221 workers exposed to DEHP in the plant was also conducted. Eight deaths occurred in the cohort compared with expected values of 15.9 and 17.0 for city and country, respectively (Thiess et al., 1978c). This study is considered inadequate with respect to the risk assessment due to small cohort size, short follow-up, and low exposure levels.

Three epidemiological studies on neurological symptoms in workers exposed to phthalate esters, including DEHP, by inhalation are available. However, due to several limitations including lack of an appropriate referent group, small size of the exposed population, inadequate documentation, and mixed exposure to other substances than DEHP, these studies are considered inadequate with respect to risk assessment.

A morbidity study was conducted in the USSR of 147 workers at a PVC-processing plant (Milkow Milkov et al., 1973). The workers were exposed to a mixture of phthalates, including DEHP as a minor constituent. Tricresyl phosphate (a neurotoxin) was a component of the incombustible materials produced in 10-20% of machines assigned to various workers. The total phthalate air concentrations recorded varied between 1.7 and 66 mg/m3. No referent group was included in the study. Frequent complaints of ill-effects were made by those exposed to phthalates. A high incidence of pain in the upper and lower extremities was reported in 57% of those employed for 6-10 years and 82% of those employed for more than 10 years.

Polyneuropathy was evident in 47 workers (32%); the incidence increased with length of employment. Another 22 workers (15%) were said to have functional disorders (not specified) of the nervous system. Vestibular abnormalities were evident in 63 workers (78%) of 81 workers specifically examined.

In a cross-sectional study, symptoms and signs of polyneuropathy were reported in 12 out of 23 workers at a plant for phthalate production in Italy (Gilioli et al., 1978). The workers were exposed to a mixture of phthalates, including DEHP, but also, to a lesser degree, to the corresponding alcohols and to phthalic anhydride. Total phthalate air concentrations recorded varied between 1 and 60 mg/m3. No referent group was included in the study. The authors concluded that no definite conclusion could be drawn from the study because of the limited number of workers examined. The study is reported in Italian with an abstract in English.

In a study involving a Swedish PVC-processing factory, 54 male workers were examined for peripheral nervous system symptoms and clinical signs. The workers were exposed mainly to DEHP, di-isodecyl phthalate, and butylbenzyl phthalate (Nielsen et al., 1985). They were divided into three groups of approximately equal size and with mean phthalate exposures of 0.1, 0.2, or 0.7 mg/m3. Some workers displayed various peripheral nervous system symptoms and signs, but these were not related to the level of exposure. None of the workers reported symptoms indicating work-related obstructive lung disease. Neither did conventional lung function test results show any association with exposure levels. Some biochemical parameters (haemoglobin, alpha-1-antitrypsin, and immunoglobulin A) showed exposure-related associations.

Conclusion: the available studies in humans is inadequate for risk assessment.