Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Although this study was not conducted in accordance with current international guidelines or GLP, in accordance with REACH Annex XI, Section 1.1.2, the study was conducted under sound scientific principles of teratogenicity assessment and adequate documentation of the study is provided. The study is therefore considered adequate for fulfilling this endpoint and for risk assessment purposes.

Data source

Reference
Reference Type:
publication
Title:
The inhalation toxicity of phenylglycidyl ether: Reproduction, mutagenic, teratogenic and cytogenetic studies
Author:
James B. Terrill
Year:
1982
Bibliographic source:
Terrill, J. B., Lee, K. P., Culik, R., and Kennedy Jr, G.L. (1982) The inhalation of phenylglycidyl ether: Reproduction, mutagenic, teratogenic, and cytogenetic studies.

Materials and methods

Principles of method if other than guideline:
Pregnant rats were exposed to 3 inhalatory concentrations (in addition to an untreated control) of PGE between the 4th and 15th day of gestation. After the last exposure the animals were sacrificed and the fetuses were assessed for skeletal abnormalities and soft tissue abnormalities. Body weights and lengths, the number of implantations, live fetuses, and resorptions per litter were also recorded.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2,3-epoxypropyl phenyl ether
EC Number:
204-557-2
EC Name:
2,3-epoxypropyl phenyl ether
Cas Number:
122-60-1
Molecular formula:
C9H10O2
IUPAC Name:
2-(phenoxymethyl)oxirane
Details on test material:
PGE purity was 99.6 % with trace amounts of phenol and diglycidyl ether as determined by gas chromatography.

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
inhalation: vapour
Type of inhalation exposure (if applicable):
whole body
Vehicle:
air
Details on exposure:
The test atmosphere was generated by syringe-driving unheated liquid into a tube furnace. The furnace tube (2 in. i.d. x 24 in. length, stainless steel) was constructed in such a way that the wall temperature of the delivery tube and the pure nitrogen stream (10 L/min) were the same temperature, 310 degrees celsius. The nitrogen-PGE atmosphere was delivered directly to the exposure chamber.
Exposures were run in 5 cubic metre chambers. Satisfactory chamber temperature (< 32 degrees celsius) and oxygen levels were maintained by the 2000 L/min inlet air velocity.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
Chamber atmospheres were monitored for PGE and phenol by UV analysis of impinger samples. Typically a 1 L/min sample was drawn through 15 ml og 0.1 N NaOH in 50:50 ethanol:water for 10 minutes. At 5 ppm (v/v), this solution has an absorbance of 0.4 (1 cm cell) at lambda max of 270nm. Phenol has a lambda max at 288 nm and can be detected at 5 % or greater of the PGE concentration (minimum sensitivity: 1 ppm of PGE, phenol >/= 0.05 ppm; 5 ppm, phenol >/= 0.25 ppm; 12 ppm, phenol >/= 0.6 ppm) using the analytical procedure.
Samples were taken hourly and the final concentrations were calculated on a time-weighted-average (TWA) basis (+/- σ).
Details on mating procedure:
Not reported
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1.7 ± 0.2 ppm TWA
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
5.7 ± 0.6 ppm TWA
Basis:
analytical conc.
Remarks:
Doses / Concentrations:
11.5 ± 3.0 ppm
Basis:
analytical conc.
Control animals:
yes

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
No unusual clinical signs were observed in the PGE treated females and the body weight data (Table 1) indicated no adverse effect. Each group was composed of 25 female rats observed to have mated. The actual number of rats observed pregnant at death ranged from 21 (high dose) to 24 (control and low dose). This distribution might suggest a dose-related decrease in the incidence of pregnancy although both the degree of response and the background incidence in this rat strain make it difficult to ascribe this finding to chemical exposure. The numbers of implantations, live fetuses, and resorptions were similar in all groups.

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
Fetuses from all treatment groups were similar in length and weight, and all appeared normal upon gross examination as well as following evaluations of internal and skeletal development.

Effect levels (fetuses)

Dose descriptor:
NOAEC
Effect level:
>= 12 ppm
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Table 1. Effect of inhalation exposure to phenylglycidyl ether on the outcome of pregnancy and fetal development of the rat

Parameter

Exposure levels of phenylglycidyl ether

Control

2 ppm

6 ppm

12 ppm

Females bred

25

25

25

25

Females pregnant (%)

24 (96)

24 (96)

23 (92)

21 (84)

Corpora Lutea/pregnant female

11.1 ± 2.1a

10.7 ± 1.8

11.2 ± 1.9

10.7 ± 2.7

Implantations/litter

9.5 ± 1.7

9.3 ± 2.2

9.8 ± 1.0

9.2 ± 1.9

Live fetuses/litter

9.0 ± 2.1

8.9 ± 2.3

9.5 ± 1.0

8.0 ± 1.9

Litters with early resorptions (%)

8 (33.3)

7 (29.2)

6 (26.1)

6 (28.6)

Litters with late resorptions (%)

1 (4.2)

0

0

0

Litters with partial resorptions (%)

9 (37.5)

7 (29.2)

6 (26.1)

6 (28.6)

Resorptions/litter with resorptions

1.3 ± 0.6

1.3 ± 0.5

1.0 ± 0.0

1.3 ± 0.5

Initial body weight of pregnant female

168.3 ± 8.5

171.2 ± 11.6

172.5 ± 7.9

107.2 ± 10.3

Final body weight of pregnant female

289.0 ± 17.9

283.8 ± 22.0

290.7 ± 21.4

279.4 ± 20.7

Fetal crown-rump length (cm)

3.8 ± 0.2

3.7 ± 0.1

3.7 ± 0.2

3.7 ± 0.2

Fetal weight (g)

4.1 ± 0.5

4.1 ± 0.4

4.1 ± 0.4

4.2 ± 0.3

Applicant's summary and conclusion

Conclusions:
No teratogenic effects were observed in this study with inhalation dose levels up to 12 ppm.