Registration Dossier

Administrative data

developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was subjected to a Quality Assurance inspection but there is no information regarding compliance with GLP requirements. Nevertheless the study was well conducted and reported and is considered reliable.
Reason / purpose:
reference to same study

Data source

Reference Type:
review article or handbook
American Petroleum Institute
Bibliographic source:
ROBUST SUMMARY OF NFORMATION ON Distillate Fuels pag 58-60

Materials and methods

Test guideline
no guideline available
not specified
Principles of method if other than guideline:
The API procedure is defined in: Any other information on materials and Methods
GLP compliance:
not specified

Test material

Details on test material:
Boiling range (ASTM D-56) : 372-656° F
Flash point (ASTM D-56) : 136° F
Wt. Sulphur %: 0.1
Viscosity @ 100° F (ASTM D-445): 2.4 cSt
Hydrocarbon types identified by mass spectrometry were:
Paraffins : 42.7 Wt. %
Cycloparaffins 33.4 Wt %
Monocycloparaffins 23.4
Dicycloparaffins 8.0
Tricycloparaffins 2.0
Aromatics 23.9 Wt. %
Alkylbenzenes 9.7
Indans & tetralins 4.8
Dinaphthenobenzenes 1.3
Biphenyls etc. 1.3
Fluorenes etc. 0.7
Tricyclic aromatics 0.8

Test animals


Administration / exposure

Route of administration:
Type of inhalation exposure (if applicable):
not specified
not specified
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
Exposures were from day 6 through day 15 of gestation
Frequency of treatment:
Exposures were for 6 hours each day
Duration of test:
On day 20 of gestation the rats were killed
Doses / concentrationsopen allclose all
Doses / Concentrations:
100 ppm
no data
Doses / Concentrations:
400 ppm
no data
No. of animals per sex per dose:
Control animals:

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
Effect level:
ca. 401.5 ppm
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

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

Effect levels (fetuses)

Dose descriptor:
Effect level:
ca. 401.5 ppm
Based on:
test mat.
Basis for effect level:
other: teratogenicity

Fetal abnormalities

not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

After analysis of samples collected during the exposure the mean chamber concentrations of diesel fuel were found to be 0, 101.8 (± 2.4) and 401.5 (± 15.39) ppm. There were no deaths during the study and all animals were normal in appearance throughout. At necropsy two 400 ppm animals had dark mottled lungs and one 100 ppm animal had two pups with a common placenta. Neither of these observations are considered to be treatment- related. Body weights were not affected by exposure to the test material. Food consumption of treated and control animals was similar at the time periods examined except for the 400 ppm group which had a reduced food intake during the gestation period, days 7-15 only. No treatment-related changes were observed on observation of the uterine contents. There was no difference in sex ratios attributable to exposure to test material.

The actual numbers were:

 Exposure Males   Females
 0 ppm  29 32 
 101.8 ppm  35 37 
 401.5 ppm  35 25 

No treatment-related differences were found in any of the following parameters:

Nidation index (females with implantations/bred)

Females dying prior to cesarean section

Live litters Implantation sites (for each uterine horn)

Resorptions Litters with resorptions

Dead fetuses

Litters with dead fetuses

Live fetuses/implantation site

Mean live litter size

Average fetal weight

Examination of the offspring at delivery revealed no visible abnormalities except for subcutaneous hematomas which occurred as follows:

0 ppm group 1

101.8 ppm group 4

401.5 ppm group 4

There were no abnormalities found in the soft tissues of the fetuses after examination of the Bouin's fixed specimens. Some changes were observed during the skeletal examination of the stained fetuses. The "unusual changes" shown in the following table consisted of retarded bone ossification and were not malformations as such. It was noted in the report that such changes, although not normal, were frequently observed in 20 day old fetuses of the strain and source of rat used in the study. The report concluded that neither the frequency nor the character of the changes indicated an adverse effect on fetal growth and development or a teratogenic potential.

Exposure (ppm) Fetuses examined Fetuses normal Fetuses with commonly found changes Fetuses with unusual skeletal variations
0 127 (16)  70 (16) 50 (14)  7 (3) 
101.8  155 (19)  68 (16) 70 (18)  17 (8) 
401.5  128 (16)  66 (16) 62 (15)  0 (0) 

Figures in parenthesis indicate No. of litters

Applicant's summary and conclusion