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Toxicological information

Developmental toxicity / teratogenicity

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Administrative data

Endpoint:
developmental toxicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2003
Reliability:
1 (reliable without restriction)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
2003
Report Date:
2003

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
EPA OTS 798.4900 (Prenatal Developmental Toxicity Study)
GLP compliance:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Name: 1,2-dichloropropane

Test animals

Species:
rat
Strain:
Sprague-Dawley

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Duration of treatment / exposure:
GD 6 - 15 inclusive
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0 (corn oil), 10, 30 or 125 mg/kg bwt/d
Basis:

Control animals:
yes, concurrent vehicle

Results and discussion

Results: maternal animals

Effect levels (maternal animals)

Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw (total dose)
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Effect levels (fetuses)

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Dose descriptor:
NOAEL
Effect level:
125 mg/kg bw (total dose)
Basis for effect level:
other: teratogenicity
Dose descriptor:
NOAEL
Effect level:
30 mg/kg bw (total dose)
Basis for effect level:
other: fetotoxicity

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Any other information on results incl. tables

Mean analysed concentrations of PDC were 5.0 (0.0), 15.0 (0.0) and 62.5 (2.0) mg/ml (SD in brackets).

Maternal observations

Clinical signs (ie decreased movement and muscle tone, increased lacrimation, decreased extensor reflex and increased salivation) were present in high dose animals on GD 6 and to a lesser extent on GD 7. Despite the transitory nature of these changes, they appeared indicative of an adverse effect in dams from the high dose group. No clinical effects were seen on other days in the high dose group, or on any day in the mid- or low dose animals.

Body weights were slightly (3-5%) but significantly lower in high dose dams throughout the study. Body weight gain was decreased significantly in high dose dams on GD 6-9, and although comparable to control during the mid- and latter stages of pregnancy the overall weight increase in the 125 mg/kg bwt/day group was approx. 30% lower than controls on GD 6-16 (that is, during the dosing period). Food consumption was reduced approx. 25% on GD 6-9, and water consumption increased by the same amount on GD 9-12 and 12-15.

There were no significant effects on absolute or relative organ weights, or on uterine weights or pregnancy parameters (including number of litters, corpora lutea per dam, implantations per dam, live fetuses per litter, resorptions, fetal bwt, etc).

Fetal observations

A low incidence of malformations was present in all groups, with no qualitative or quantitative increase in litters from treated dams. Overall there was no indication that PDC was a teratogen.

Fetal variations were present in both control and treated groups. The only treatment-related effect was a significant increase in the incidence of delayed ossification of the bones of the skull among fetuses from the high dose group. Interestingly, the occurrence of this observation was most common in high dose litters containing 16 or more pups. All other parameters were comparable to the controls.

Applicant's summary and conclusion

Conclusions:
Under the conditions of the study, mild fetotoxicity (as evidenced by decreased ossification of the bones of the skull) was noted in litters from dams given 125 mg/kg bwt PDC/day. This effect was most common in the larger litters, and was co-incident with significant reductions in body
weight gain and food consumption. It is concluded that the NOAEL for both maternal and fetal toxicity was 30 mg/kg bwt/day.